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Sample records for dosimetry plasma pharmacokinetics

  1. Pharmacokinetics and dosimetry, an introduction

    International Nuclear Information System (INIS)

    Notari, R.E.

    1981-01-01

    Classical pharmacokinetic techniques attempt to quantify the time course for drug in the body by assaying samples of blood or urine as a function of time. The mathematical descriptions that have emerged from this approach have proven extremely valuable to both drug research and drug therapy. Since the monitoring of patients' drug blood levels by obtaining a few small blood samples at key times is clinically practical, individualization of dosage regimens has become a reality. This has dramatically altered certain types of drug therapy. These improvements are limited to cases wherein biological response can be related to drug blood levels since the mathematics are capable only of describing the sampled fluids. Non-sampled fluids are considered as additional compartments or pools and described collectively using kinetic equations for mass balance. This limits progress in those areas of research which require assessment of the relationship of specific organ contents to that of the blood. The author suggests that radiopharmaceutical techniques which can provide the time course in specific organs might be coupled with classical pharmacokinetic approaches to provide insight not previously achieved

  2. Pharmacokinetics and dosimetry of the anti-androgen vinclozolin after oral administration inthe rat

    Science.gov (United States)

    Vinclozolin (V) is a fungicide with antiandrogenic properties. To determine the pharmacokinetics and dosimetry of V, adult male rats were administered an oral dose of V (100 mg/kg) in corn oil and sacrificed over time after dosing. V and its metabolites were analyzed in serum and...

  3. 11C-ORM-13070, a novel PET ligand for brain α2C-adrenoceptors: radiometabolism, plasma pharmacokinetics, whole-body distribution and radiation dosimetry in healthy men

    International Nuclear Information System (INIS)

    Luoto, Pauliina; Oikonen, Vesa; Arponen, Eveliina; Helin, Semi; Virta, Jere; Virtanen, Kirsi; Roivainen, Anne; Suilamo, Sami; Herttuainen, Jukka; Hietamaeki, Johanna; Holopainen, Aila; Rouru, Juha; Sallinen, Jukka; Kailajaervi, Marita; Peltonen, Juha M.; Scheinin, Mika; Volanen, Iina; Rinne, Juha O.

    2014-01-01

    11 C-labelled 1-[(S)-1-(2,3-dihydrobenzo[1,2]dioxin-2-yl)methyl] -4-(3-methoxy-methylpyridin-2- yl)-piperazine ( 11 C-ORM-13070) is a novel PET tracer for imaging of α 2C -adrenoceptors in the human brain. Brain α 2C -adrenoceptors may be therapeutic targets in several neuropsychiatric disorders, including depression, schizophrenia and Alzheimer's disease. To validate the use of 11 C-ORM-13070 in humans, we investigated its radiometabolism, pharmacokinetics, whole-body distribution and radiation dose. Radiometabolism was studied in a test-retest setting in six healthy men. After intravenous injection of 11 C-ORM-13070, blood samples were drawn over 60 min. Plasma samples were analysed by radio-HPLC for intact tracer and its radioactive metabolites. Metabolite-corrected plasma time-activity curves were used for calculation of pharmacokinetics. In a separate group of 12 healthy men, the whole-body distribution of 11 C-ORM-13070 and radiation exposure were investigated by dynamic PET/CT imaging without blood sampling. Two radioactive metabolites of 11 C-ORM-13070 were detected in human arterial plasma. The proportion of unchanged 11 C-ORM-13070 decreased from 81 ± 4 % of total radioactivity at 4 min after tracer injection to 23 ± 4 % at 60 min. At least one of the radioactive metabolites penetrated into red blood cells, while the parent tracer remained in plasma. The apparent elimination rate constant and corresponding half-life of unchanged 11 C-ORM-13070 in arterial plasma were 0.0117 ± 0.0056 min -1 and 73.6 ± 35.8 min, respectively. The organs with the highest absorbed doses were the liver (12 μSv/MBq), gallbladder wall (12 μSv/MBq) and pancreas (9.1 μSv/MBq). The mean effective dose was 3.9 μSv/MBq, with a range of 3.6 - 4.2 μSv/MBq. 11 C-ORM-13070 was rapidly metabolized in human subjects after intravenous injection. The effective radiation dose of 11 C-ORM-13070 was in the same range as that of other 11 C-labelled brain receptor tracers. An injection

  4. {sup 11}C-ORM-13070, a novel PET ligand for brain α{sub 2C}-adrenoceptors: radiometabolism, plasma pharmacokinetics, whole-body distribution and radiation dosimetry in healthy men

    Energy Technology Data Exchange (ETDEWEB)

    Luoto, Pauliina; Oikonen, Vesa; Arponen, Eveliina; Helin, Semi; Virta, Jere; Virtanen, Kirsi; Roivainen, Anne [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); Suilamo, Sami [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); Turku University Hospital, Department of Oncology and Radiotherapy, Turku (Finland); Herttuainen, Jukka; Hietamaeki, Johanna; Holopainen, Aila; Rouru, Juha; Sallinen, Jukka [Orion Pharma, Espoo and Turku (Finland); Kailajaervi, Marita [GE Healthcare, Turku Imanet, Turku (Finland); Peltonen, Juha M.; Scheinin, Mika; Volanen, Iina [University of Turku, CRST, Turku (Finland); Rinne, Juha O. [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); University of Turku, CRST, Turku (Finland); TYKSLAB, Unit of Clinical Pharmacology, Turku (Finland); University of Turku and Turku University Hospital, Division of Clinical Neurosciences, Turku (Finland)

    2014-10-15

    {sup 11}C-labelled 1-[(S)-1-(2,3-dihydrobenzo[1,2]dioxin-2-yl)methyl] -4-(3-methoxy-methylpyridin-2- yl)-piperazine ({sup 11}C-ORM-13070) is a novel PET tracer for imaging of α{sub 2C}-adrenoceptors in the human brain. Brain α{sub 2C}-adrenoceptors may be therapeutic targets in several neuropsychiatric disorders, including depression, schizophrenia and Alzheimer's disease. To validate the use of {sup 11}C-ORM-13070 in humans, we investigated its radiometabolism, pharmacokinetics, whole-body distribution and radiation dose. Radiometabolism was studied in a test-retest setting in six healthy men. After intravenous injection of {sup 11}C-ORM-13070, blood samples were drawn over 60 min. Plasma samples were analysed by radio-HPLC for intact tracer and its radioactive metabolites. Metabolite-corrected plasma time-activity curves were used for calculation of pharmacokinetics. In a separate group of 12 healthy men, the whole-body distribution of {sup 11}C-ORM-13070 and radiation exposure were investigated by dynamic PET/CT imaging without blood sampling. Two radioactive metabolites of {sup 11}C-ORM-13070 were detected in human arterial plasma. The proportion of unchanged {sup 11}C-ORM-13070 decreased from 81 ± 4 % of total radioactivity at 4 min after tracer injection to 23 ± 4 % at 60 min. At least one of the radioactive metabolites penetrated into red blood cells, while the parent tracer remained in plasma. The apparent elimination rate constant and corresponding half-life of unchanged {sup 11}C-ORM-13070 in arterial plasma were 0.0117 ± 0.0056 min{sup -1} and 73.6 ± 35.8 min, respectively. The organs with the highest absorbed doses were the liver (12 μSv/MBq), gallbladder wall (12 μSv/MBq) and pancreas (9.1 μSv/MBq). The mean effective dose was 3.9 μSv/MBq, with a range of 3.6 - 4.2 μSv/MBq. {sup 11}C-ORM-13070 was rapidly metabolized in human subjects after intravenous injection. The effective radiation dose of {sup 11}C-ORM-13070 was in the same range

  5. Internal Dosimetry and the pharmacokinetic of the Cuban Kit of Methoxy-Isobutyl-Isonitrile (MIBI) marked with 99mTc

    International Nuclear Information System (INIS)

    Torres, L.A.; Pereztol, O.; Rodriguez, J.L.; Alvarez, I.; Fraxedas, R.; Mesa, G.; Rodriguez, R.

    1998-01-01

    The objective of the present work consisted on evaluating the Internal Dosimetry and the pharmacokinetic of the Cuban Kit of Methoxy-Isobutyl-Isonitrile (MIBI) marked with 99mTc. In the dosimetry studies and biodistribution five healthy volunteers were included and in the pharmacokinetic studies five patients were included with less than 5% of probability of suffering illness of artery coronary

  6. Application of pharmacokinetic modeling to the radiation dosimetry of hepatobiliary agents

    International Nuclear Information System (INIS)

    Loberg, M.D.; Buddemeyer, E.U.

    1981-01-01

    Dosimetry calculations based on biodistribution data from lower animal species often inadequately approximate the true dosimetry in humans and seldom apply in the presence of human pathology. An alternative approach is to use animal data for the limited purpose of developing a pharmacokinetic model describing the various compartments and their interconnecting pathways. To the extent that components are similarly connected in man, the model can be used to compute cumulative concentrations (μCi-h/gm) in humans by using the compartment masses and rate constants appropriate for man. In this manner dose estimates can be obtained which are less dependent upon the species from which the model was derived. The altered radiation dose in certain disease states having a known relationship to the model can also be predicted with confidence. This work reports the development in dogs of a four-compartment model which accurately describes the in-vivo distribution of Tc/sup 99m/-HIDA. The pharmacokinetic model was used to predict the kinetics of the HIDA analog which would yield clinically useful information, while minimizing patient radiation exposure

  7. Plasma and cerebrospinal fluid pharmacokinetics of flurbiprofen in children

    Science.gov (United States)

    Kumpulainen, Elina; Välitalo, Pyry; Kokki, Merja; Lehtonen, Marko; Hooker, Andrew; Ranta, Veli-Pekka; Kokki, Hannu

    2010-01-01

    AIMS This study was designed to characterize paediatric pharmacokinetics and central nervous system exposure of flurbiprofen. METHODS The pharmacokinetics of flurbiprofen were studied in 64 healthy children aged 3 months to 13 years, undergoing surgery with spinal anaesthesia. Children were administered preoperatively a single dose of flurbiprofen intravenously as prodrug (n = 27) or by mouth as syrup (n = 37). A single cerebrospinal fluid (CSF) sample (n = 60) was collected at the induction of anaesthesia, and plasma samples (n = 304) before, during and after the operation (up to 20 h after administration). A population pharmacokinetic model was built using the NONMEM software package. RESULTS Flurbiprofen concentrations in plasma were well described by a three compartment model. The apparent bioavailability of oral flurbiprofen syrup was 81%. The estimated clearance (CL) was 0.96 l h−1 70 kg−1. Age did not affect the clearance after weight had been included as a covariate. The estimated volume of distribution at steady state (Vss) was 8.1 l 70 kg−1. Flurbiprofen permeated into the CSF, reaching concentrations that were seven-fold higher compared with unbound plasma concentrations. CONCLUSIONS Flurbiprofen pharmacokinetics can be described using only weight as a covariate in children above 6 months, while more research is needed in neonates and in younger infants. PMID:20840447

  8. Pharmacokinetics and dosimetry of the antiandrogen vinclozolin after oral administration in the rat.

    Science.gov (United States)

    Sierra-Santoyo, Adolfo; Castañeda-Hernández, Gilberto; Harrison, Randy A; Barton, Hugh A; Hughes, Michael F

    2008-11-01

    Vinclozolin (V) is a fungicide with antiandrogenic properties. To determine the pharmacokinetics and dosimetry of V, adult male rats were administered an oral dose of V (100 mg/kg) in corn oil and sacrificed over time after dosing. V and its metabolites were analyzed in serum and tissues by high performance liquid chromatography/diode array detector/mass spectrometer. V, 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), and five other metabolites were detected in serum and tissues. One metabolite was identified as 3',5'-dichloro-2,3,4-trihydroxy-2-methylbutylanilide (M5). The mean serum concentration data for V were fitted to a one-compartment model for kinetic analysis. At 2 h, V serum concentration peaked; whereas only trace levels were detected at 24 h (t(1/2 elim) = 3.6 h). V was detected in all tissues and preferentially accumulated in fat. M1 serum levels increased until 8 h, being at least 2-fold higher than those of V at this time, and then declined with a t(1/2) = 3.3 h. M5 was the main metabolite in serum and tissues. Serum M5 levels were 5-fold higher than V and 2-fold greater than M1 at all times. At 48 h, M5 remained the main metabolite (t(1/2 elim) = 13.1 h). Liver and kidney exhibited the highest levels of M5, V, and M1. M2 and 3,5-dichloroaniline had the lowest levels of V metabolites in serum and tissues. V is well absorbed, extensively metabolized and widely distributed. M5, the most abundant V metabolite, may be used as an exposure biomarker for pharmacokinetic modeling. These results may clarify the relationship between toxicity and tissue dose of V and its metabolites.

  9. Safety, pharmacokinetic and dosimetry evaluation of the proposed thrombus imaging agent 99mTc-DI-DD-3B6/22-80B3 Fab'

    International Nuclear Information System (INIS)

    Macfarlane, David J.; Smart, Richard C.; Tsui, Wendy W.; Gerometta, Michael; Eisenberg, Paul R.; Scott, Andrew M.

    2006-01-01

    99m Tc-DI-DD-3B6/22-80B3 (Thromboview, hereafter abbreviated to 99m Tc-DI-80B3 Fab') is a humanised, radiolabelled monoclonal antibody Fab' fragment with high affinity and specificity for the D-dimer domain of cross-linked fibrin. The purpose of this study was to evaluate the safety, pharmacokinetics and dosimetry of four increasing doses of 99m Tc-DI-80B3 Fab' in healthy volunteers. Thirty-two healthy volunteers (18-70 years; 16 male, 16 female) received a single intravenous injection of 0.5, 1.0, 2.0 or 4.0 mg of 99m Tc-DI-80B3 Fab'. Safety outcomes (vital signs, electrocardiography, haematology, biochemistry, adverse events and development of human anti-human antibodies) were assessed up to 30 days post injection. Blood and urine samples were collected up to 48 h post injection. Gamma camera images were acquired at 0.5, 1, 2, 4, 6 and 24 h post injection. Dosimetry was performed using standard MIRD methodology. No adverse events considered to be drug related were observed. Human anti-human antibody was not detectable in any subject during the follow-up period. 99m Tc-DI-80B3 Fab' had a rapid initial plasma clearance (t 1/2 α=1 h). The pharmacokinetic profile of the Fab' fragment was generally linear across the four dose cohorts. By 24 h, 30-35% of the administered radioactivity appeared in the urine. There was marked renal accumulation with time, but no specific uptake was identified within other normal tissues. The effective dose was 9 mSv/750 MBq. (orig.)

  10. Pharmacokinetics and normal organ dosimetry following intraperitoneal rhenium-186-labeled monoclonal antibody

    International Nuclear Information System (INIS)

    Breitz, H.B.; Durham, J.S.; Fisher, D.R.

    1995-01-01

    Pharmacokinetics, biodistribution and radiation dose estimates following intraperitoneal administration of a 186 Re-labeled murine antibody, NR-LU-10, were assessed in 27 patients with advanced ovarian cancer. Quantitative gamma camera imaging and gamma counting of serum and intraperitoneal fluid radioactivity were used to obtain data for dosimetry estimation. The MIRD intraperitoneal model was used to estimate dose to normal organs from radioactivity within the peritoneal cavity. The absorbed dose to normal peritoneum was estimated in two ways: from the gamma camera activity and peritoneal fluid samples. Serum activity peaked at 44 hr and depended on the concentration of radioactivity in the peritoneal fluid. Mean cumulative urinary excretion of 186 Re was 50% by 140 hr. Estimates of radiation absorbed dose to normal organs in rad/mCi administered (mean ± s.d.) were whole body 0.7 ± 0.3; marrow 0.4 ±0.1; liver 1.9 ±0.9; lungs 1.3 ± 0.7; kidneys 0.2 ± 0.2; intestine 0.2 ±0.2. Peritoneal surface dose estimates varied depending on the volume of fluid infused and the method of dose determination. Using gamma camera data, the peritoneal dose ranged for 7 to 36 rad/mCi. Using peritoneal fluid sample data, the dose ranged from 2 to 25 rad/mCi. Significant myelosuppression was observed at marrow doses above 100 rad. Noninvasive methods of dose estimation for intraperitoneal administration of radioimmunoconjugates provide reasonable estimates when compared with previously described methods. 31 refs., 6 figs., 2 tabs

  11. HPLC assay for ethiofos in plasma: Application to pharmacokinetics in the beagle dog

    International Nuclear Information System (INIS)

    Swynnerton, N.F.; Mangold, D.J.; Ludden, T.M.

    1985-01-01

    An HPLC assay for ethiofos [S-2-(3-amino-propylamino)ethyl phosphorothioate, WR 2727] in plasma is presented. Its application to the development of pharmacokinetic parameters following IV administration of the drug to beagle dogs is demonstrated and preliminary pharmacokinetics of four dosings will be presented. Following a dose of 150 mg kg -1 , the plasma concentration versus time profile was best described by a two-compartment pharmacokinetics model. Mean pharmacokinetic parameters were: terminal elimination half-life = 16.0 minutes, volume of central compartment = 129 mL kg -1 , and clearance = 11.0 mL min -1 kg -1

  12. Dosimetry

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    The purpose of ionizing radiation dosimetry is the measurement of the physical and biological consequences of exposure to radiation. As these consequences are proportional to the local absorption of energy, the dosimetry of ionizing radiation is based on the measurement of this quantity. Owing to the size of the effects of ionizing radiation on materials in all of these area, dosimetry plays an essential role in the prevention and the control of radiation exposure. Its use is of great importance in two areas in particular where the employment of ionizing radiation relates to human health: radiation protection, and medical applications. Dosimetry is different for various reasons: owing to the diversity of the physical characteristics produced by different kinds of radiation according to their nature (X- and γ-photons, electrons, neutrons,...), their energy (from several keV to several MeV), the orders of magnitude of the doses being estimated (a factor of about 10 5 between diagnostic and therapeutic applications); and the temporal and spatial variation of the biological parameters entering into the calculations. On the practical level, dosimetry poses two distinct yet closely related problems: the determination of the absorbed dose received by a subject exposed to radiation from a source external to his body (external dosimetry); and the determination of the absorbed dose received by a subject owing to the presence within his body of some radioactive substance (internal dosimetry)

  13. Internal radiation dosimetry, pharmacokinetics and biodistribution of the 99mTc labeled ior egf/r3 monoclonal antibody

    International Nuclear Information System (INIS)

    Torres, L.A.; Perera, A.; Ramos, M.; Hernandez, A.; Iznaga, N.; Solano, M.E.; Alvarez, I.; Rodriguez, J.L.

    2001-01-01

    The aim of this work was to assess the internal radiation dosimetry, human pharmacokinetics and biodistribution of the 99m Tc-labeled murine monoclonal antibody (MAb) ior egf/r3, used for diagnosis of epithelial tumors. Five patients were included in this study. Multiple blood and urine samples were collected and sequential anterior and posterior whole-body scintigraphies up to 24 hr post-injection were acquired from all patients. The internal radiation dosimetry was estimated using the methods developed by the Medical Internal Radiation Dosimetry (MIRD) committee. Raw data were computed from operations between scintigraphic images and regions of interest (ROI). The residence times of the activity on the source organs were computed to assess the absorbed dose by 24 target organs. The dosimetric results showed that liver, gallbladder and spleen received the higher absorbed dose. The computed mean values were 0.69 mGy/MBq, 0.19mGy/MBq and 0.37 mGy/MBq, respectively. The mean value of effective dose was 1,2E-01 mSv/MBq and the effective equivalent dose was 9,2E-02 mSv/MBq. The pharmacokinetics and biodistribution results showed that this compound has a biexponential plasmatic and blood clearance with a rapid biodistribution phase and a slower elimination phase. This compound was excreted by the urinary and hepatobiliary systems. Liver was the principal target organ of this product showing a great retention of the MAb. These dosimetric results have allowed to use the ior egf/r3 kit in a safe and controlled way. (author)

  14. Dosimetry

    International Nuclear Information System (INIS)

    Rezende, D.A.O. de

    1976-01-01

    The fundamental units of dosimetry are defined, such as exposure rate, absorbed dose and equivalent dose. A table is given of relative biological effectiveness values for the different types of radiation. The relation between the roentgen and rad units is calculated and the concepts of physical half-life, biological half-life and effective half-life are discussed. Referring to internal dosimetry, a mathematical treatment is given to β particle-and γ radiation dosimetry. The absorbed dose is calculated and a practical example is given of the calculation of the exposure and of the dose rate for a gama source [pt

  15. Plasma paracetamol concentrations and pharmacokinetics following rectal administration in neonates and young infants

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing; O'Brien, K; Morton, N S

    1999-01-01

    Despite widespread use in children pharmacokinetic data about paracetamol are relatively scarce, not the least in the youngest age groups. This study aimed to describe plasma paracetamol concentrations and pharmacokinetics of a single rectal paracetamol dose in neonates and young infants....

  16. Pharmacokinetics and radiation dosimetry of 99mTc-3PRGD2 in healthy individuals: A pilot study

    International Nuclear Information System (INIS)

    Cheng Guanghui; Gao Shi; JI Tiefeng; Ma Qingjie; Wang Qing; Jia Bing; Chen Zuowei

    2012-01-01

    99m Tc-3PRGD 2 is a new SPECT radiotracer for several tumor imaging with high uptake where integrin α v β 3 is highly expressed. This pilot study was to assess the safety, biodistribution and radiation dosimetry of 99m Tc-3PRGD 2 in healthy volunteers. The 10 healthy male volunteers were injected with 99m Tc-3PRGD 2 (786.7±55.8 MBq, 19.1-24.2 mCi). Baseline measurements of vital signs, laboratory safety tests and 12-lead electrocardiogram were recorded before and after injection. Blood and urine samples were collected and radiation counts were obtained at various time points. Whole-body scans and ROIs of identified organs were used for visual analysis and estimating the radiation dosimetry. No adverse reactions were found during the study. 99m Tc-3PRGD 2 exhibited a rapid clearance from the blood with less than 45% of the initial dosage at 10 min after injection and gradual increasing radioactivity in urine with (52.9±6)% of original dose at 1440 min. The whole-body imaging showed high radioactive accumulation in bladder. And the highest 99m Tc-3PRGD 2 uptake was found in the kidneys (3.50×10 -2 mSv/MBq). The 99m Tc-3PRGD 2 exhibited good pharmacokinetic properties and little radiation burden. This study showed that 99m Tc-3PRGD 2 would be a safe and attractive SPECT agent in clinic applications. (authors)

  17. Chiral Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine and its Phase I and II Metabolites following Controlled Administration to Humans.

    OpenAIRE

    Steuer Andrea E; Schmidhauser Corina; Schmid Yasmin; Rickli Anna; Liechti Matthias E; Kraemer Thomas

    2015-01-01

    Generally, pharmacokinetic studies on 3,4-methylenedioxymethamphetamine (MDMA) in blood have been performed after conjugate cleavage, without taking into account that phase II metabolites represent distinct chemical entities with their own effects and stereoselective pharmacokinetics. The aim of the present study was to stereoselectively investigate the pharmacokinetics of intact glucuronide and sulfate metabolites of MDMA in blood plasma after a controlled single MDMA dose. Plasma samples fr...

  18. Dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Hurst, G S; Ritchie, R H; Sanders, F W; Reinhardt, P W; Auxier, J A; Wagner, E B; Callihan, A D; Morgan, K Z [Health Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN (United States)

    1962-03-15

    The methods of dosimetry used for investigation of the doses received by the individuals exposed in the Yugoslav accident were essentially those used in connection with the Oak Ridge Y-12 accident. An outline of the general scheme is as follows: When fast neutrons enter the human body, most of these are moderated to thermal energy and a small fraction of these are captured by a (n, gamma) process in Na sup 2 sup 3 , giving rise to Na sup 2 sup 4 , which by virtue of its emission of high-energy gamma rays with a half life of 14.8 h, is easily detected. It has been shown that the probability of capture, making Na sup 2 sup 4 , is not a strong function of the energy of the fast neutrons and that the probability of capture for neutrons is higher in the fast region than in the thermal region. Thus, the uniform distribution of Na sup 2 sup 3 in the human body provides an excellent means of normalizing the neutron exposure of an individual. in particular, for a given neutron energy spectrum the fast neutron dose is proportional to the ratio Na sup 2 sup 4 /Na sup 2 sup 3 in the body or in the blood system. This method of normalization is quite important in the dosimetry of radiation accidents since no assumptions need be made about the exact location of an individual at the time of the energy release. The importance of this fact can be made clear by reference to the Y-12 accident where it was shown by calculation of the neutron dose based on the known number of fissions and the stated location of the individual that one of the surviving individuals would have received a dose several times the lethal value. To accomplish the measurements described, the zero power R sub B reactor was operated in two ranges of power level, 'low' power and 'high 'power. Neutron leakage spectrum was obtained by multigroup approximation of the Boltzmann transport equation. Prompt gamma rays from fission products, from capture in the moderator and fuel cladding as well as in tank walls are given

  19. Dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Hurst, G S; Ritchie, R H; Sanders, F W; Reinhardt, P W; Auxier, J A; Wagner, E B; Callihan, A D; Morgan, K Z [Health Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN (United States)

    1962-03-01

    The methods of dosimetry used for investigation of the doses received by the individuals exposed in the Yugoslav accident were essentially those used in connection with the Oak Ridge Y-12 accident. An outline of the general scheme is as follows: When fast neutrons enter the human body, most of these are moderated to thermal energy and a small fraction of these are captured by a (n, {gamma}) process in Na{sup 23}, giving rise to Na{sup 24}, which by virtue of its emission of high-energy gamma rays with a half life of 14.8 h, is easily detected. It has been shown that the probability of capture, making Na{sup 24}, is not a strong function of the energy of the fast neutrons and that the probability of capture for neutrons is higher in the fast region than in the thermal region. Thus, the uniform distribution of Na{sup 23} in the human body provides an excellent means of normalizing the neutron exposure of an individual. in particular, for a given neutron energy spectrum the fast neutron dose is proportional to the ratio Na{sup 24}/Na{sup 23} in the body or in the blood system. This method of normalization is quite important in the dosimetry of radiation accidents since no assumptions need be made about the exact location of an individual at the time of the energy release. The importance of this fact can be made clear by reference to the Y-12 accident where it was shown by calculation of the neutron dose based on the known number of fissions and the stated location of the individual that one of the surviving individuals would have received a dose several times the lethal value. To accomplish the measurements described, the zero power R{sub B} reactor was operated in two ranges of power level, 'low' power and 'high 'power. Neutron leakage spectrum was obtained by multigroup approximation of the Boltzman transport equation. Prompt gamma rays from fission products, from capture in the moderator and fuel cladding as well as in tank walls are given. A summary of the 4{pi

  20. Pharmacokinetic modeling: Prediction and evaluation of route dependent dosimetry of bisphenol A in monkeys with extrapolation to humans

    International Nuclear Information System (INIS)

    Fisher, Jeffrey W.; Twaddle, Nathan C.; Vanlandingham, Michelle; Doerge, Daniel R.

    2011-01-01

    A physiologically based pharmacokinetic (PBPK) model was developed for bisphenol A (BPA) in adult rhesus monkeys using intravenous (iv) and oral bolus doses of 100 μg d6-BPA/kg (). This calibrated PBPK adult monkey model for BPA was then evaluated against published monkey kinetic studies with BPA. Using two versions of the adult monkey model based on monkey BPA kinetic data from and , the aglycone BPA pharmacokinetics were simulated for human oral ingestion of 5 mg d16-BPA per person (Völkel et al., 2002). Völkel et al. were unable to detect the aglycone BPA in plasma, but were able to detect BPA metabolites. These human model predictions of the aglycone BPA in plasma were then compared to previously published PBPK model predictions obtained by simulating the Völkel et al. kinetic study. Our BPA human model, using two parameter sets reflecting two adult monkey studies, both predicted lower aglycone levels in human serum than the previous human BPA PBPK model predictions. BPA was metabolized at all ages of monkey (PND 5 to adult) by the gut wall and liver. However, the hepatic metabolism of BPA and systemic clearance of its phase II metabolites appear to be slower in younger monkeys than adults. The use of the current non-human primate BPA model parameters provides more confidence in predicting the aglycone BPA in serum levels in humans after oral ingestion of BPA. -- Highlights: ► A bisphenol A (BPA) PBPK model for the infant and adult monkey was constructed. ► The hepatic metabolic rate of BPA increased with age of the monkey. ► The systemic clearance rate of metabolites increased with age of the monkey. ► Gut wall metabolism of orally administered BPA was substantial across all ages of monkeys. ► Aglycone BPA plasma concentrations were predicted in humans orally given oral doses of deuterated BPA.

  1. Prediction and evaluation of route dependent dosimetry of BPA in rats at different life stages using a physiologically based pharmacokinetic model

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiaoxia, E-mail: Xiaoxia.Yang@fda.hhs.gov; Doerge, Daniel R.; Fisher, Jeffrey W.

    2013-07-01

    Bisphenol A (BPA) has received considerable attention throughout the last decade due to its widespread use in consumer products. For the first time a physiologically based pharmacokinetic (PBPK) model was developed in neonatal and adult rats to quantitatively evaluate age-dependent pharmacokinetics of BPA and its phase II metabolites. The PBPK model was calibrated in adult rats using studies on BPA metabolism and excretion in the liver and gastrointestinal tract, and pharmacokinetic data with BPA in adult rats. For immature rats the hepatic and gastrointestinal metabolism of BPA was inferred from studies on the maturation of phase II enzymes coupled with serum time course data in pups. The calibrated model predicted the measured serum concentrations of BPA and BPA conjugates after administration of 100 μg/kg of d6-BPA in adult rats (oral gavage and intravenous administration) and postnatal days 3, 10, and 21 pups (oral gavage). The observed age-dependent BPA serum concentrations were partially attributed to the immature metabolic capacity of pups. A comparison of the dosimetry of BPA across immature rats and monkeys suggests that dose adjustments would be necessary to extrapolate toxicity studies from neonatal rats to infant humans. - Highlights: • A PBPK model predicts the kinetics of bisphenol A (BPA) in young and adult rats. • BPA metabolism within enterocytes is required for fitting of oral BPA kinetic data. • BPA dosimetry in young rats is different than adult rats and young monkeys.

  2. Prediction and evaluation of route dependent dosimetry of BPA in rats at different life stages using a physiologically based pharmacokinetic model

    International Nuclear Information System (INIS)

    Yang, Xiaoxia; Doerge, Daniel R.; Fisher, Jeffrey W.

    2013-01-01

    Bisphenol A (BPA) has received considerable attention throughout the last decade due to its widespread use in consumer products. For the first time a physiologically based pharmacokinetic (PBPK) model was developed in neonatal and adult rats to quantitatively evaluate age-dependent pharmacokinetics of BPA and its phase II metabolites. The PBPK model was calibrated in adult rats using studies on BPA metabolism and excretion in the liver and gastrointestinal tract, and pharmacokinetic data with BPA in adult rats. For immature rats the hepatic and gastrointestinal metabolism of BPA was inferred from studies on the maturation of phase II enzymes coupled with serum time course data in pups. The calibrated model predicted the measured serum concentrations of BPA and BPA conjugates after administration of 100 μg/kg of d6-BPA in adult rats (oral gavage and intravenous administration) and postnatal days 3, 10, and 21 pups (oral gavage). The observed age-dependent BPA serum concentrations were partially attributed to the immature metabolic capacity of pups. A comparison of the dosimetry of BPA across immature rats and monkeys suggests that dose adjustments would be necessary to extrapolate toxicity studies from neonatal rats to infant humans. - Highlights: • A PBPK model predicts the kinetics of bisphenol A (BPA) in young and adult rats. • BPA metabolism within enterocytes is required for fitting of oral BPA kinetic data. • BPA dosimetry in young rats is different than adult rats and young monkeys

  3. Pharmacokinetic profile of voriconazole in a critically ill patient on therapeutic plasma exchange

    NARCIS (Netherlands)

    Spriet, I.; Bruggemann, R.J.M.; Annaert, P.; Meersseman, P.; Wijngaerden, E. van; Lagrou, K.; Willems, L.

    2013-01-01

    BACKGROUND: Extracorporeal removal of drugs during therapeutic plasma exchange (TPE) can lead to decreased efficacy, as shown in several reports discussing altered pharmacokinetics (PKs) of antibiotics during TPE. In particular, drugs with a low volume of distribution or a high protein binding are

  4. Plasma and urine, pharmacokinetics of the dopamine agonist alpha-dihydroergocryptine in patients with hepatic dysfunction

    NARCIS (Netherlands)

    Althaus, M; de Mey, C; Ezan, E; Ciecko-Michalska, [No Value; Kostka-Trabkal, E; Goszcz, A; Retzow, A

    Objective: The aim of this study was to evaluate the pharmacokinetic behavior of unchanged alpha -dihydroergocryptine (DHEC, Almirid (R), Desitin Arzneimittel GmbH, Hamburg, Germany, under licence of Polichem S.A., Luxembourg) and total DHEC (unchanged DHEC and pooled metabolites) in plasma and

  5. Safety, pharmacokinetic and dosimetry evaluation of the proposed thrombus imaging agent {sup 99m}Tc-DI-DD-3B6/22-80B3 Fab'

    Energy Technology Data Exchange (ETDEWEB)

    Macfarlane, David J. [Royal Brisbane and Women' s Hospital, Department of Nuclear Medicine, Brisbane (Australia); Smart, Richard C. [St George Hospital, Department of Nuclear Medicine, Sydney (Australia); Tsui, Wendy W. [St George Hospital, Department of Nuclear Medicine, Sydney (Australia); University of New South Wales, School of Medicine, Sydney (Australia); Gerometta, Michael [AGEN Biomedical Limited, Research and Development, Brisbane (Australia); Eisenberg, Paul R. [Eli Lilly Company, Lilly Research Laboratories, Indianapolis (United States); Scott, Andrew M. [Austin Health, Centre for PET, Melbourne (Australia); Ludwig Institute for Cancer Research, Melbourne (Australia)

    2006-06-15

    {sup 99m}Tc-DI-DD-3B6/22-80B3 (Thromboview, hereafter abbreviated to {sup 99m}Tc-DI-80B3 Fab') is a humanised, radiolabelled monoclonal antibody Fab' fragment with high affinity and specificity for the D-dimer domain of cross-linked fibrin. The purpose of this study was to evaluate the safety, pharmacokinetics and dosimetry of four increasing doses of {sup 99m}Tc-DI-80B3 Fab' in healthy volunteers. Thirty-two healthy volunteers (18-70 years; 16 male, 16 female) received a single intravenous injection of 0.5, 1.0, 2.0 or 4.0 mg of {sup 99m}Tc-DI-80B3 Fab'. Safety outcomes (vital signs, electrocardiography, haematology, biochemistry, adverse events and development of human anti-human antibodies) were assessed up to 30 days post injection. Blood and urine samples were collected up to 48 h post injection. Gamma camera images were acquired at 0.5, 1, 2, 4, 6 and 24 h post injection. Dosimetry was performed using standard MIRD methodology. No adverse events considered to be drug related were observed. Human anti-human antibody was not detectable in any subject during the follow-up period. {sup 99m}Tc-DI-80B3 Fab' had a rapid initial plasma clearance (t{sub 1/2}{alpha}=1 h). The pharmacokinetic profile of the Fab' fragment was generally linear across the four dose cohorts. By 24 h, 30-35% of the administered radioactivity appeared in the urine. There was marked renal accumulation with time, but no specific uptake was identified within other normal tissues. The effective dose was 9 mSv/750 MBq. (orig.)

  6. Preclinical acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of ["1"8F]fluorocholine in mice

    International Nuclear Information System (INIS)

    Silveira, Marina B.; Ferreira, Soraya M.Z.M.D.; Nascimento, Leonardo T.C.; Costa, Flávia M.; Mendes, Bruno M.; Ferreira, Andrea V.; Malamut, Carlos; Silva, Juliana B.; Mamede, Marcelo

    2016-01-01

    ["1"8F]Fluorocholine (["1"8F]FCH) has been proven to be effective in prostate cancer. Since ["1"8F]FCH is classified as a new radiopharmaceutical in Brazil, preclinical safety and efficacy data are required to support clinical trials and to obtain its approval. The aim of this work was to perform acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of ["1"8F]FCH. The results could support its use in nuclear medicine as an important piece of work for regulatory in Brazil. - Highlights: • Data demonstrated the high quality, safety and effectiveness of ["1"8F]FCH. • ["1"8F]FCH preclinical profile is in accordance with previously published. • Toxicity, distribution, kinetics and radiation dosimetry were well characterized. • The results are important for regulatory issues in Brazil and other countries.

  7. Human pharmacokinetics, biodistribution and dosimetry of the kit of monoclonal antibody IOR EGF/R3 labelled with {sup 99m} Tc

    Energy Technology Data Exchange (ETDEWEB)

    Torres, L.A.; Ramos, M.; Perera, A.; Hernandez, A.; Iznaga, M.E. N. [Solano, Ivette Alvarez, Jose L. Rodriguez. Centro de InvestigacionesClinicas. 34 no.4501 e/45 y 47 Kohly, Playa, C. Habana (Cuba)

    1998-12-31

    The aim of this work was to assess the human pharmacokinetics, biodistribution and dosimetry of the {sup 99m} Tc-labeled MAb ior egf/r3. Five patients were included in the biodistribution and dosimetric studies and three in the pharmacokinetic analysis. Multiple blood and urine samples we recollected and sequential anterior and posterior whole-body scintigraphies u pto 24 hr post-injection were performed to all patients . The internal radiation dosimetry was estimated from gamma camera imaging data using the methods developed by the Medical Internal radiation dosimetry (MIRD)committee. Raw data were computed from operations between gamma graphic images and regions of interest (ROI) using the Bio-Dose software and time-activity curves were calculated in order to determine the residence times of the source organs. The Pharmacokinetics and Biodistribution results showed that this compound have a bio exponential plasmatic and blood clearance with a rapid biodistribution phase of 9.1 {+-} 8.4 min and 12.2{+-}4.4 min, respectively, and a slower elimination phase of 6.6 {+-} 1.6 hr and 10.8 {+-} 6.8 hr. respectively. The urinary and hepatobiliary excretion showed 4.7 {+-} 0.4 % and 9.9 {+-} 1.8 % of the total administered dose,eliminated by these ways. Liver was the target organ of this product and had an uptake peak at 1 hr post-injection (61.2%) and a great retention of the MAb(T 1/2 eff = 5.3 hr, T 1/2 Biol. = 45.0 hr). The dosimetric results showed that liver, gallbladder and spleen received the higher absorbed. The effective dose and the effective equivalent dose were 1,2E-01 mSv/MBq and 9,2E-02 mSv/MBq respectively. These results allow to see the i or egf/r3 kit in a safe and controlled way. (Author)

  8. Dosimetry of x-rays from high-temperature plasmas

    International Nuclear Information System (INIS)

    Yamamoto, Takayoshi; Abe, Nobuyuki; Kawanishi, Masaharu

    1980-01-01

    Study on the dosimetry of ionizing radiations, especially of X-rays, emitted from high-temperature plasms has been made. As to the unpolarized Bremsstrahlung, a brief method to estimate electron temperatures with TLD is described and evaluation of average energy and current of the run-away electrons in the turbulent heating Tokamak is made by observing the half-value layer of the emitted X-rays and the total exposure per one shot of the Tokamak discharge. As to the polarized one, it is shown that the anisotropic electron temperature is related to the degree of polarization of the X-rays. Furthermore, reference is made to the possibility of developing such X-ray generators as can emit nearly monochromatic X-rays (characteristic X-rays) or polarized ones arbitrarily. (author)

  9. Personal dosimetry calculations by means of radio pharmacokinetic and gamma graphic studies

    International Nuclear Information System (INIS)

    Arteaga de Murphy, C.; Ferro F, G.; Pedraza L, M.; Montoya M, C.E.

    2000-01-01

    The determination of the absorbed radiation dose is an essential factor to assess the risk to patient with a diagnostic study of nuclear medicine but over all it is indispensable for predicting the efficiency of individualized radio pharmacotherapy and weighting up the risk/benefit of the treatment. In studies for diagnostic or/and treatment of nuclear medicine generally the absorbed radiation dose is not determined for each patient since the methods for estimating it are laborious and include complex models such biological as mathematical, therefore is very important to have a relatively easy method. The obtained data with 99m Tc-Abp., a new radiopharmaceutical for osseous gammagraphy, were used with the purpose of exemplifying a practical method. The radio pharmacokinetic parameters were determined during 24 hours in 10 health voluntaries and serial gamma grams were taken during two hours to another voluntaries. The obtained data were used to estimate, with the MIRDOSE3 computer program, the absorbed radiation dose in an osseous dragging with 99m Tc-Abp. is low: 0.00472 m Gy/MBq to osseous marrow, mainly to the vertebral column and femur, and 0.00169 m Gy/ MBq to whole body. These data are lower than those informed in the medical literature for other bis phosphonates. (Author)

  10. Indinavir Population Pharmacokinetics in Plasma and Cerebrospinal Fluid

    OpenAIRE

    Letendre, Scott L.; Capparelli, Edmund V.; Ellis, Ronald J.; McCutchan, J. Allen

    2000-01-01

    Plasma and cerebrospinal fluid (CSF) indinavir concentrations were measured by high-performance liquid chromatography. The median concentration in plasma exceeded that in CSF 10-fold. The modeled CSF curve was flat at 155 nM, and the estimated ratio of the areas under the CSF and plasma concentration-time curves was 6%. We conclude that CSF indinavir concentrations are lower than levels in plasma but exceed the clinical 95% inhibitory concentration range.

  11. Relationship between pharmacokinetics of 5-FU in plasma and in saliva, and toxicity of 5-fluorouracil/folinic acid

    NARCIS (Netherlands)

    Jansman, FGA; Coenen, JLLM; De Graaf, JC; Tobi, H; Sleijfer, DT; Brouwers, JRBJ

    2002-01-01

    Background: Dose adaptation based on pharmacokinetic parameters has been shown to decrease toxicity of some 5-fluorouracil(5-FU)-based continuous infusion regimens. Patients and Methods: In the present study the relationship between 5-FU pharmacokinetics in plasma and in saliva, and toxicity was

  12. Determination and pharmacokinetic study of catechin in rat plasma by HPLC

    Directory of Open Access Journals (Sweden)

    Li Xie

    2011-11-01

    Full Text Available A high performance liquid chromatographic method was developed and validated for the quantitative determination of catechin in rat plasma and its pharmacokinetic study after intragastric administration of Catechu and Xiongdanjiangre Wan into SD rats. Plasma samples were prepared by protein precipitation using methanol–5% aqueous zinc sulfate (70:30, v/v as precipitant. Chromatographic separation was achieved on Hypersil C18 column (250 mm×4.6 mm, 10 μm with acetonitrile–water–triethylamine (6:94:0.3, v/v/v, pH 4.0±0.1, adjusted with phosphoric acid as mobile phase, followed by a UV detection at 207 nm. Good linearity was obtained over the range of 0.143–7.15 mg/L of catechin, with correlation coefficient of 0.9992. The method was simple, sensitive, accurate and reproducible and has been successfully applied to the pharmacokinetic study of catechin in rat plasma. Keywords: HPLC, Determination, Pharmacokinetic, Catechin, Rat, Plasma

  13. Pharmacokinetic behavior of marbofloxacin in plasma from chickens at different seasons

    Directory of Open Access Journals (Sweden)

    Natalia Francisca Urzúa Pizarro1,

    2017-10-01

    Full Text Available The purpose of this study was to evaluate the differences in the disposition and plasma pharmacokinetic behavior of marbofloxacin (MAR in broiler chickens at different seasons. Chicken broilers (n = 345 were used, in lots of 5 individuals, divided into 6 groups depending on the way of administration, intravenous or oral (dose 2 mg/kg and the test period. Post-administration plasma samples were obtained at different times, intravenously (0.08 to 24 hours and orally (0.25 to 120 hours. A liquid-liquid extraction of MAR was performed by high-performance liquid chromatography (HPLC with a fluorescent detector. The plasma concentrations obtained at the different sampling times of each season, were analyzed with ANOVA and pharmacokinetic analysis was conducted with the PK Solution 2.0 software. The concentration of marbofloxacin in plasma was significantly lower in winter and summer than in spring, with MAR being detected in winter up to 72 hours post-application, coinciding with the differences in MAR pharmacokinetics parameters with increase in the average residence time (MRT is 9.4 hours in winter. Increased clearance MAR in summer (7.5 ml/min/kg coincides with MRT 6.3 hours. Finally, the oral bioavailability of MAR is lower in summer and winter (86 ± 1.7% and 78 ± 3.1% than in spring (94 ± 5.2 %. There are differences in the disposition and plasma pharmacokinetic behavior of MAR applied orally in broiler chickens, coinciding with the physiological changes in the thermoregulation of birds, considering its correct therapeutic management and contributing to provide safe food for human consumption.

  14. Development of a Physiologically Based Pharmacokinetic and Pharmacodynamic Model to Determine Dosimetry and Cholinesterase Inhibition for a Binary Mixture of Chlorpyrifos and Diazinon in the Rat

    Energy Technology Data Exchange (ETDEWEB)

    Timchalk, Chuck; Poet, Torka S.

    2008-05-01

    Physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models have been developed and validated for the organophosphorus (OP) insecticides chlorpyrifos (CPF) and diazinon (DZN). Based on similar pharmacokinetic and mode of action properties it is anticipated that these OPs could interact at a number of important metabolic steps including: CYP450 mediated activation/detoxification, and blood/tissue cholinesterase (ChE) binding/inhibition. We developed a binary PBPK/PD model for CPF, DZN and their metabolites based on previously published models for the individual insecticides. The metabolic interactions (CYP450) between CPF and DZN were evaluated in vitro and suggests that CPF is more substantially metabolized to its oxon metabolite than is DZN. These data are consistent with their observed in vivo relative potency (CPF>DZN). Each insecticide inhibited the other’s in vitro metabolism in a concentration-dependent manner. The PBPK model code used to described the metabolism of CPF and DZN was modified to reflect the type of inhibition kinetics (i.e. competitive vs. non-competitive). The binary model was then evaluated against previously published rodent dosimetry and ChE inhibition data for the mixture. The PBPK/PD model simulations of the acute oral exposure to single- (15 mg/kg) vs. binary-mixtures (15+15 mg/kg) of CFP and DZN at this lower dose resulted in no differences in the predicted pharmacokinetics of either the parent OPs or their respective metabolites; whereas, a binary oral dose of CPF+DZN at 60+60 mg/kg did result in observable changes in the DZN pharmacokinetics. Cmax was more reasonably fit by modifying the absorption parameters. It is anticipated that at low environmentally relevant binary doses, most likely to be encountered in occupational or environmental related exposures, that the pharmacokinetics are expected to be linear, and ChE inhibition dose-additive.

  15. Isolation, characterization, and in rats plasma pharmacokinetic study of a new triterpenoid saponin from Dianthus superbus.

    Science.gov (United States)

    Ren, Yina; Xu, Xiaobao; Zhang, Qianlan; Lu, Yongzhuang; Li, Ximin; Zhang, Lin; Tian, Jingkui

    2017-02-01

    One new oleanolic acid triterpenoid saponin, 3-O-β-D-glucopyranosyl olean-11, 13(18)-diene-23,28-dioic acid, (hereafter referred to as DS-1) was isolated from the traditional Chinese medicinal plant Dianthus superbus (D. superbus). DS-1 plays an important role in the bioactivity of D. superbus. Thus, a sensitive, reliable and accurate reversed-phased liquid chromatography with tandem mass spectrometry (LC-MS/MS) in negative ion mode was developed and validated for the quantification and pharmacokinetic study of DS-1 in rats plasma. The pharmacokinetic profile showed that DS-1 was rapidly absorbed and eliminated in plasma, indicating that significant accumulation of the compound in biological specimen is unlikely. In addition, poor absorption into systemic circulation was observed after oral administration of DS-1, resulting in low absolute bioavailability (0.92 %).

  16. Safety, pharmacokinetics, metabolism and radiation dosimetry of 18F-tetrafluoroborate (18F-TFB) in healthy human subjects.

    Science.gov (United States)

    Jiang, Huailei; Schmit, Nicholas R; Koenen, Alex R; Bansal, Aditya; Pandey, Mukesh K; Glynn, Robert B; Kemp, Bradley J; Delaney, Kera L; Dispenzieri, Angela; Bakkum-Gamez, Jamie N; Peng, Kah-Whye; Russell, Stephen J; Gunderson, Tina M; Lowe, Val J; DeGrado, Timothy R

    2017-10-27

    18 F-Tetrafluoroborate ( 18 F-TFB) is a promising iodide analog for PET imaging of thyroid cancer and sodium/iodide symporter (NIS) reporter activity in viral therapy applications. The aim of this study was to evaluate the safety, pharmacokinetics, biodistribution, and radiation dosimetry of high-specific activity 18 F-TFB in healthy human subjects. 18 F-TFB was synthesized with specific activity of 3.2 ± 1.3 GBq/μmol (at the end of synthesis). Dynamic and whole-body static PET/CT scans over 4 h were performed after intravenous administration of 18 F-TFB (333-407 MBq) in four female and four male healthy volunteers (35 ± 11 years old). Samples of venous blood and urine were collected over the imaging period and analyzed by ion-chromatography HPLC to determine tracer stability. Vital signs and clinical laboratory safety assays were measured to evaluate safety. 18 F-TFB administration was well tolerated with no significant findings on vital signs and no clinically meaningful changes in clinical laboratory assays. Left-ventricular blood pool time-activity curves showed a multi-phasic blood clearance of 18 F-radioactivity with the two rapid clearance phases over the first 20 min, followed by a slower clearance phase. HPLC analysis showed insignificant 18 F-labeled metabolites in the blood and urine over the length of the study (4 h). High uptakes were seen in the thyroid, stomach, salivary glands, and bladder. Urinary clearance of 18 F-TFB was prominent. Metabolic stability was evidenced by low accumulation of 18 F-radioactivity in the bone. Effective doses were 0.036 mSv/MBq in males and 0.064 mSv/MBq in females (p = 0.08, not significant). This initial study in healthy human subjects showed 18 F-TFB was safe and distributed in the human body similar to other iodide analogs. These data support further translational studies with 18 F-TFB as NIS gene reporter and imaging biomarker for thyroid cancer and other disease processes that import iodide.

  17. Pharmacokinetics, biodistribution and dosimetry of {sup 99m}Tc-labeled anti-human epidermal growth factor receptor humanized monoclonal antibody R3 in rats

    Energy Technology Data Exchange (ETDEWEB)

    Escobar, Normando Iznaga; Morales, Alejo Morales; Duconge, Jorge; Torres, Idania Caballero; Fernandez, Eduardo; Gomez, Jose A

    1998-01-01

    The pharmacokinetics, biodistribution and dosimetry of {sup 99m}Tc-labeled anti-human epidermal growth factor receptor (anti-hEGF-r) humanized monoclonal antibody (MAb) R3 was investigated following intravenous injection in normal Wistar rats. Serum disappearance curves were best fit by a two-compartment model having a mean distribution half-life (t{sub (1(2{alpha}}{sub ))}) of 0.250 h and a mean elimination (t{sub (1(2{beta}}{sub ))}) of 13.89 h. Among the various organs, a little accumulation of the radiolabeled antibody was found only in kidneys. Biodistribution and dosimetry studies in humans were performed by extrapolation of the animal data to humans. Absorbed dose to normal organs and the remainder of the whole body were estimated using the medical internal radiation dose formula, and dose contributions from radioactivity in transit through the gastrointestinal tract were estimated using a compartment model. Extrapolated values of radiation absorbed dose to normal organs in rads per millicurie administered were whole body, 0.0085; lower large intestine wall, 0.0898; small intestine, 0.0530; upper large intestine wall, 0.0731; and kidneys, 0.0455. The effective dose equivalent predicted was 0.0162 rem/mCi and the effective dose was found to be 0.015 rem/mCi. On the basis of the pharmacokinetics, biodistribution and internal radiation dosimetry information obtained in this study, a diagnostic phase I clinical trial with {sup 99m}Tc-labeled humanized MAb R3 conjugate in patients should be supported.

  18. Pharmacokinetics, biodistribution and dosimetry of 99mTc-labeled anti-human epidermal growth factor receptor humanized monoclonal antibody R3 in rats

    International Nuclear Information System (INIS)

    Escobar, Normando Iznaga; Morales, Alejo Morales; Duconge, Jorge; Torres, Idania Caballero; Fernandez, Eduardo; Gomez, Jose A.

    1998-01-01

    The pharmacokinetics, biodistribution and dosimetry of 99m Tc-labeled anti-human epidermal growth factor receptor (anti-hEGF-r) humanized monoclonal antibody (MAb) R3 was investigated following intravenous injection in normal Wistar rats. Serum disappearance curves were best fit by a two-compartment model having a mean distribution half-life (t (1(2α)) ) of 0.250 h and a mean elimination (t (1(2β)) ) of 13.89 h. Among the various organs, a little accumulation of the radiolabeled antibody was found only in kidneys. Biodistribution and dosimetry studies in humans were performed by extrapolation of the animal data to humans. Absorbed dose to normal organs and the remainder of the whole body were estimated using the medical internal radiation dose formula, and dose contributions from radioactivity in transit through the gastrointestinal tract were estimated using a compartment model. Extrapolated values of radiation absorbed dose to normal organs in rads per millicurie administered were whole body, 0.0085; lower large intestine wall, 0.0898; small intestine, 0.0530; upper large intestine wall, 0.0731; and kidneys, 0.0455. The effective dose equivalent predicted was 0.0162 rem/mCi and the effective dose was found to be 0.015 rem/mCi. On the basis of the pharmacokinetics, biodistribution and internal radiation dosimetry information obtained in this study, a diagnostic phase I clinical trial with 99m Tc-labeled humanized MAb R3 conjugate in patients should be supported

  19. Biodegradable nanoparticles for improved kidney bioavailability of rhein: preparation, characterization, plasma, and kidney pharmacokinetics.

    Science.gov (United States)

    Wei, Yinghui; Luo, Xiaoting; Guan, Jiani; Ma, Jianping; Zhong, Yicong; Luo, Jingwen; Li, Fanzhu

    2017-11-01

    The aim of this work is to develop biodegradable nanoparticles for improved kidney bioavailability of rhein (RH). RH-loaded nanoparticles were prepared using an emulsification solvent evaporation method and fully characterized by several techniques. Kidney pharmacokinetics was assessed by implanting a microdialysis probe in rat's kidney cortex. Blood samples were simultaneously collected (via femoral artery) for assessing plasma pharmacokinetics. Optimized nanoparticles were small, with a mean particle size of 132.6 ± 5.95 nm, and homogeneously dispersed. The charge on the particles was nearly zero, the encapsulation efficiency was 62.71 ± 3.02%, and the drug loading was 1.56 ± 0.15%. In vitro release of RH from the nanoparticles showed an initial burst release followed by a sustained release. Plasma and kidney pharmacokinetics showed that encapsulation of RH into nanoparticles significantly increased its kidney bioavailability (AUC kidney /AUC plasma  = 0.586 ± 0.072), clearly indicating that nanoparticles are a promising strategy for kidney drug delivery.

  20. Population Pharmacokinetics of Meropenem in Plasma and Subcutis in Patients on Extracorporeal Membrane Oxygenation Treatment

    DEFF Research Database (Denmark)

    Hanberg, Pelle; Öbrink-Hansen, Kristina; Thorsted, Anders

    2018-01-01

    The objectives of this study were to describe meropenem pharmacokinetics (PK) in plasma and/or subcutaneous adipose tissue (SCT) in critically ill patients receiving ECMO treatment, and to develop a population PK model to simulate alternative dosing regimens and modes of administration. We...... conducted a prospective observational study. Ten patients on ECMO treatment received meropenem (1 or 2 g) intravenously over 5 min every 8 hours. Serial SCT concentrations were determined using microdialysis and compared with plasma concentrations. A population PK model of SCT and plasma data was developed...... infusion would be needed for 100%fT>MIC and 100%fT>4xMIC to be obtained. Meropenem plasma and SCT concentrations were associated with estimated creatinine-clearance (eCLCr). Simulations showed that in patients with increased eCLCr, dose increment or continuous infusion may be needed to obtain therapeutic...

  1. Determination of flurbiprofen in human plasma by gas chromatography with mass spectrometry and its pharmacokinetics.

    Science.gov (United States)

    Yilmaz, Bilal; Sahin, Huseyin; Akba, Vedat; Erdem, Ali Fuat

    2014-01-01

    This paper describes a GCIMS method for the determination of flurbiprofen in human plasma. Flurbiprofen and internal standard ibuprofen were extracted from plasma by using a liquid-liquid extraction method. Derivatization was carried out using N-Methyl-N-(trimethylsilyl)trifluoroacetamide. The calibration curve was linear between the concentration range of 0.10 and 5.0 microg/mL. Intraday and interday precision values for flurbiprofen in plasma were less than 5.49%, and accuracy (relative error) was better than 5.33%. The extraction recoveries of flurbiprofen from human plasma were between 93.6 and 98.6%. The LOD and LOQ of flurbiprofen were 0.03 and 0.10 microg/mL, respectively. This assay was applied to determine the pharmacokinetic parameters of flurbiprofen in healthy Turkish volunteers who had been given 100 mg of flurbiprofen.

  2. Human pharmacokinetics, biodistribution and dosimetry of the kit of monoclonal antibody IOR EGF/R3 labelled with 99m Tc

    International Nuclear Information System (INIS)

    Torres, L.A.; Ramos, M.; Perera, A.; Hernandez, A.; Iznaga, M.E. N.

    1998-01-01

    The aim of this work was to assess the human pharmacokinetics, biodistribution and dosimetry of the 99m Tc-labeled MAb ior egf/r3. Five patients were included in the biodistribution and dosimetric studies and three in the pharmacokinetic analysis. Multiple blood and urine samples we recollected and sequential anterior and posterior whole-body scintigraphies u pto 24 hr post-injection were performed to all patients . The internal radiation dosimetry was estimated from gamma camera imaging data using the methods developed by the Medical Internal radiation dosimetry (MIRD)committee. Raw data were computed from operations between gamma graphic images and regions of interest (ROI) using the Bio-Dose software and time-activity curves were calculated in order to determine the residence times of the source organs. The Pharmacokinetics and Biodistribution results showed that this compound have a bio exponential plasmatic and blood clearance with a rapid biodistribution phase of 9.1 ± 8.4 min and 12.2±4.4 min, respectively, and a slower elimination phase of 6.6 ± 1.6 hr and 10.8 ± 6.8 hr. respectively. The urinary and hepatobiliary excretion showed 4.7 ± 0.4 % and 9.9 ± 1.8 % of the total administered dose,eliminated by these ways. Liver was the target organ of this product and had an uptake peak at 1 hr post-injection (61.2%) and a great retention of the MAb(T 1/2 eff = 5.3 hr, T 1/2 Biol. = 45.0 hr). The dosimetric results showed that liver, gallbladder and spleen received the higher absorbed. The effective dose and the effective equivalent dose were 1,2E-01 mSv/MBq and 9,2E-02 mSv/MBq respectively. These results allow to see the i or egf/r3 kit in a safe and controlled way. (Author)

  3. Carprofen pharmacokinetics in plasma and in control and inflamed canine tissue fluid using in vivo ultrafiltration.

    Science.gov (United States)

    Messenger, K M; Wofford, J A; Papich, M G

    2016-02-01

    Measurement of unbound drug concentrations at their sites of action is necessary for accurate PK/PD modeling. The objective of this study was to determine the unbound concentration of carprofen in canine interstitial fluid (ISF) using in vivo ultrafiltration and to compare pharmacokinetic parameters of free carprofen concentrations between inflamed and control tissue sites. We hypothesized that active concentrations of carprofen would exhibit different dispositions in ISF between inflamed vs. normal tissues. Bilateral ultrafiltration probes were placed subcutaneously in six healthy Beagle dogs 12 h prior to induction of inflammation. Two milliliters of either 2% carrageenan or saline control was injected subcutaneously at each probe site, 12 h prior to intravenous carprofen (4 mg/kg) administration. Plasma and ISF samples were collected at regular intervals for 72 h, and carprofen concentrations were determined using HPLC. Prostaglandin E2 (PGE2 ) concentrations were quantified in ISF using ELISA. Unbound carprofen concentrations were higher in ISF compared with predicted unbound plasma drug concentrations. Concentrations were not significantly higher in inflamed ISF compared with control ISF. Compartmental modeling was used to generate pharmacokinetic parameter estimates, which were not significantly different between sites. Terminal half-life (T½) was longer in the ISF compared with plasma. PGE2 in ISF decreased following administration of carprofen. In vivo ultrafiltration is a reliable method to determine unbound carprofen in ISF, and that disposition of unbound drug into tissue is much higher than predicted from unbound drug concentration in plasma. However, concentrations and pharmacokinetic parameter estimates are not significantly different in inflamed vs. un-inflamed tissues. © 2015 John Wiley & Sons Ltd.

  4. A Physiologically Based Pharmacokinetic Model to Predict the Pharmacokinetics of Highly Protein-Bound Drugs and Impact of Errors in Plasma Protein Binding

    Science.gov (United States)

    Ye, Min; Nagar, Swati; Korzekwa, Ken

    2015-01-01

    Predicting the pharmacokinetics of highly protein-bound drugs is difficult. Also, since historical plasma protein binding data was often collected using unbuffered plasma, the resulting inaccurate binding data could contribute to incorrect predictions. This study uses a generic physiologically based pharmacokinetic (PBPK) model to predict human plasma concentration-time profiles for 22 highly protein-bound drugs. Tissue distribution was estimated from in vitro drug lipophilicity data, plasma protein binding, and blood: plasma ratio. Clearance was predicted with a well-stirred liver model. Underestimated hepatic clearance for acidic and neutral compounds was corrected by an empirical scaling factor. Predicted values (pharmacokinetic parameters, plasma concentration-time profile) were compared with observed data to evaluate model accuracy. Of the 22 drugs, less than a 2-fold error was obtained for terminal elimination half-life (t1/2, 100% of drugs), peak plasma concentration (Cmax, 100%), area under the plasma concentration-time curve (AUC0–t, 95.4%), clearance (CLh, 95.4%), mean retention time (MRT, 95.4%), and steady state volume (Vss, 90.9%). The impact of fup errors on CLh and Vss prediction was evaluated. Errors in fup resulted in proportional errors in clearance prediction for low-clearance compounds, and in Vss prediction for high-volume neutral drugs. For high-volume basic drugs, errors in fup did not propagate to errors in Vss prediction. This is due to the cancellation of errors in the calculations for tissue partitioning of basic drugs. Overall, plasma profiles were well simulated with the present PBPK model. PMID:26531057

  5. A physiologically based pharmacokinetic model to predict the pharmacokinetics of highly protein-bound drugs and the impact of errors in plasma protein binding.

    Science.gov (United States)

    Ye, Min; Nagar, Swati; Korzekwa, Ken

    2016-04-01

    Predicting the pharmacokinetics of highly protein-bound drugs is difficult. Also, since historical plasma protein binding data were often collected using unbuffered plasma, the resulting inaccurate binding data could contribute to incorrect predictions. This study uses a generic physiologically based pharmacokinetic (PBPK) model to predict human plasma concentration-time profiles for 22 highly protein-bound drugs. Tissue distribution was estimated from in vitro drug lipophilicity data, plasma protein binding and the blood: plasma ratio. Clearance was predicted with a well-stirred liver model. Underestimated hepatic clearance for acidic and neutral compounds was corrected by an empirical scaling factor. Predicted values (pharmacokinetic parameters, plasma concentration-time profile) were compared with observed data to evaluate the model accuracy. Of the 22 drugs, less than a 2-fold error was obtained for the terminal elimination half-life (t1/2 , 100% of drugs), peak plasma concentration (Cmax , 100%), area under the plasma concentration-time curve (AUC0-t , 95.4%), clearance (CLh , 95.4%), mean residence time (MRT, 95.4%) and steady state volume (Vss , 90.9%). The impact of fup errors on CLh and Vss prediction was evaluated. Errors in fup resulted in proportional errors in clearance prediction for low-clearance compounds, and in Vss prediction for high-volume neutral drugs. For high-volume basic drugs, errors in fup did not propagate to errors in Vss prediction. This is due to the cancellation of errors in the calculations for tissue partitioning of basic drugs. Overall, plasma profiles were well simulated with the present PBPK model. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Psychomotor effect differences between l-methamphetamine and d-methamphetamine are independent of murine plasma and brain pharmacokinetics profiles

    OpenAIRE

    Nishimura, Tetsuya; Takahata, Kazue; Kosugi, Yuri; Tanabe, Takaaki; Muraoka, Shizuko

    2017-01-01

    l-Methamphetamine has been occasionally referred to as a stimulant similar to d-methamphetamine, probably owing to insufficient comparative studies. Here, we directly compared psychomotor efficacies and pharmacokinetics of methamphetamine enantiomers in mice. Only d-methamphetamine, but not l-methamphetamine, induced stereotypy and sensitization at 1?10?mg/kg. However, plasma pharmacokinetic parameters of 10?mg/kg l-methamphetamine were ?tenfold those of 1?mg/kg d-methamphetamine. These resul...

  7. A validated bioanalytical HPLC method for pharmacokinetic evaluation of 2-deoxyglucose in human plasma.

    Science.gov (United States)

    Gounder, Murugesan K; Lin, Hongxia; Stein, Mark; Goodin, Susan; Bertino, Joseph R; Kong, Ah-Ng Tony; DiPaola, Robert S

    2012-05-01

    2-Deoxyglucose (2-DG), an analog of glucose, is widely used to interfere with glycolysis in tumor cells and studied as a therapeutic approach in clinical trials. To evaluate the pharmacokinetics of 2-DG, we describe the development and validation of a sensitive HPLC fluorescent method for the quantitation of 2-DG in plasma. Plasma samples were deproteinized with methanol and the supernatant was dried at 45°C. The residues were dissolved in methanolic sodium acetate-boric acid solution. 2-DG and other monosaccharides were derivatized to 2-aminobenzoic acid derivatives in a single step in the presence of sodium cyanoborohydride at 80°C for 45 min. The analytes were separated on a YMC ODS C₁₈ reversed-phase column using gradient elution. The excitation and emission wavelengths were set at 360 and 425 nm. The 2-DG calibration curves were linear over the range of 0.63-300 µg/mL with a limit of detection of 0.5 µg/mL. The assay provided satisfactory intra-day and inter-day precision with RSD less than 9.8%, and the accuracy ranged from 86.8 to 110.0%. The HPLC method is reproducible and suitable for the quantitation of 2-DG in plasma. The method was successfully applied to characterize the pharmacokinetics profile of 2-DG in patients with advanced solid tumors. Copyright © 2011 John Wiley & Sons, Ltd.

  8. Effect of Apium graveolens Extract Administration on the Pharmacokinetics of Captopril in the Plasma of Rats

    Directory of Open Access Journals (Sweden)

    Siska Siska

    2018-02-01

    Full Text Available Apium graveolens (celery is an edible and traditionally medicinal plant that is used worldwide, among others for the treatment of hypertension. Combining celery with antihypertensive drugs can affect the pharmacodynamics and pharmacokinetics of the latter drugs. The aim of the study is to assess the effects of administrating the celery extract on captopril pharmacokinetics. Sprague-Dawley strain rats were divided into two groups (n = 6. Group I was given captopril (10 mg/kg Body Weight (BW orally, while Group II was pretreated with celery extract orally (40 mg/kg BW an hour before administration of captopril. The blood samples were withdrawn at various intervals after drug administration. The captopril concentration was determined using liquid chromatography–mass spectrometry (LC-MS/MS and from the blood data, the values of Ke, Cmax, Tmax, T1/2, and area under the curve (AUC were calculated. The results showed that oral administration of the celery extract increased Cmax (38.67%, T1/2 (37.84%, and AUC (58.10% and decreased Ke (27.45% of captopril in Group II (celery + captopril compared with Group I (captopril. In conclusion, celery extract can alter the pharmacokinetic of captopril when given in combination. The combination might be beneficial for the treatment of hypertension, as celery causes an increase in the plasma level of captopril, which can enhance its efficacy.

  9. Metabolic and pharmacokinetic studies of scutellarin in rat plasma, urine, and feces.

    Science.gov (United States)

    Xing, Jian-feng; You, Hai-sheng; Dong, Ya-lin; Lu, Jun; Chen, Si-ying; Zhu, Hui-fang; Dong, Qian; Wang, Mao-yi; Dong, Wei-hua

    2011-05-01

    To study the metabolic and pharmacokinetic profile of scutellarin, an active component from the medical plant Erigeron breviscapus (Vant) Hand-Mazz, and to investigate the mechanisms underlying the low bioavailability of scutellarin though oral or intravenous administration in rats. HPLC method was developed for simultaneous detection of scutellarin and scutellarein (the aglycone of scutellarin) in rat plasma, urine and feces. The in vitro metabolic stability study was carried out in rat liver microsomes from different genders. After a single oral dose of scutellarin (400 mg/kg), the plasma concentrations of scutellarin and scutellarein in female rats were significantly higher than in male ones. Between the female and male rats, significant differences in AUC, t(max2) and C(max2) for scutellarin were found. The pharmacokinetic parameters of scutellarin in the urine also showed significant gender differences. After a single oral dose of scutellarin (400 mg/kg), the total percentage excretion of scutellarein in male and female rats was 16.5% and 8.61%, respectively. The total percentage excretion of scutellarin and scutellarein in the feces was higher with oral administration than with intravenous administration. The in vitro t(1/2) and CL(int) value for scutellarin in male rats was significantly higher than that in female rats. The results suggest that a large amount of ingested scutellarin was metabolized into scutellarein in the gastrointestinal tract and then excreted with the feces, leading to the extremely low oral bioavailability of scutellarin. The gender differences of pharmacokinetic parameters of scutellarin and scutellarein are due to the higher CL(int) and lower absorption in male rats.

  10. Enzyme-inducing anticonvulsants increase plasma clearance of dexmedetomidine: a pharmacokinetic and pharmacodynamic study.

    Science.gov (United States)

    Flexman, Alana M; Wong, Harvey; Riggs, K Wayne; Shih, Tina; Garcia, Paul A; Vacas, Susana; Talke, Pekka O

    2014-05-01

    Dexmedetomidine is useful during mapping of epileptic foci as it facilitates electrocorticography unlike most other anesthetic agents. Patients with seizure disorders taking enzyme-inducing anticonvulsants appear to be resistant to its sedative effects. The objective of the study was to compare the pharmacokinetic and pharmacodynamic profile of dexmedetomidine in healthy volunteers with volunteers with seizure disorders receiving enzyme-inducing anticonvulsant medications. Dexmedetomidine was administered using a step-wise, computer-controlled infusion to healthy volunteers (n = 8) and volunteers with seizure disorders (n = 8) taking phenytoin or carbamazapine. Sedation and dexmedetomidine plasma levels were assessed at baseline, during the infusion steps, and after discontinuation of the infusion. Sedation was assessed by using the Observer's Assessment of Alertness/Sedation Scale, Ramsay Sedation Scale, and Visual Analog Scale and processed electroencephalography (entropy) monitoring. Pharmacokinetic analysis was performed on both groups, and differences between groups were determined using the standard two-stage approach. A two-compartment model was fit to dexmedetomidine concentration-time data. Dexmedetomidine plasma clearance was 43% higher in the seizure group compared with the control group (42.7 vs. 29.9 l/h; P = 0.007). In contrast, distributional clearance and the volume of distribution of the central and peripheral compartments were similar between the groups. No difference in sedation was detected between the two groups during a controlled range of target plasma concentrations. This study demonstrates that subjects with seizure disorders taking enzyme-inducing anticonvulsant medications have an increased plasma clearance of dexmedetomidine as compared with healthy control subjects.

  11. [Plasma ibuprofen enantiomers and their pharmacokinetics in Beagle dogs determined by HPLC].

    Science.gov (United States)

    Wang, Hong-yan; Kong, Ai-ying; Yang, Bo; Yan, Liang-ping; Di, Xin

    2015-12-01

    A chiral high-performance liquid chromatography method was developed for the simultaneous determination of ibuprofen enantiomers in dog plasma. It was used to study the pharmacokinetics in the Beagle dog after intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen. Ketoprofen was chosen as the internal standard. After a simple precipitation using methanol as the precipitating solvent, both analytes and IS were separated on a Kromasil 100-5CHI-TBB chiral column (250 mm x4.6 mm, 5 μm) with isocratic elution using acetonitrile - 20 mmol x L(-1) phosphate buffer (pH 3.0, containing 5% methanol) (6 : 4) as the mobile phase. The detection wavelength was 220 nm. Liner calibration curves for both of the ibuprofen enantiomers were over the concentration range from 0.5 to 50 μg x mL(-1) with a lower limit of quantification of 0.5 μg x mL(-1), the accuracies were all in standard ranges. The intra- and inter- assay precisions were all below 7%. The recovery rate was 93.1% to 100.4%. The experiments proved that the method was simple, rapid and sensitive. It can be used in the quantitative determination of ibuprofen enantiomers in dog plasma. The method was used to determine the concentration of ibuprofen enantiomers in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen (9 mg x kg(-1)) and the pharmacokinetics parameters were calculated based on the concentration-time curves. The C(max) of S-ibuprofen in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen were 30.8 ± 4.7, 46.1 ± 5.9 and 20.0 ± 2.6 μg x mL(-1), respectively. In terms of the exposure of active ingredient, it revealed a significant difference between the administration of S-ibuprofen and the other two groups. The systematical R- to S- chiral inversion was discussed. Comparing the pharmacokinetic parameters at different doses, chiral inversion were 70.1% ± 36.6% and 76

  12. Plasma pharmacokinetics and synovial concentrations of S-flurbiprofen plaster in humans.

    Science.gov (United States)

    Yataba, Ikuko; Otsuka, Noboru; Matsushita, Isao; Kamezawa, Miho; Yamada, Ichimaro; Sasaki, Sigeru; Uebaba, Kazuo; Matsumoto, Hideo; Hoshino, Yuichi

    2016-01-01

    The purpose of this study is to investigate the pharmacokinetics and deep tissue penetration capability of the newly developed S-flurbiprofen plaster (SFPP) in humans. Study 1: SFPP tape-type patch (2-60 mg) was applied to the lower back for 24 h in healthy adult volunteers. S-flurbiprofen (SFP) plasma concentration was measured over time to examine SFP pharmacokinetics. Study 2: SFPP (20 mg) was applied for 12 h to the affected knee of osteoarthritis (OA) patients who were scheduled for total knee arthroplasty. Deep tissues (synovial tissue and synovial fluid) were collected during surgery to compare SFP concentrations after application of SFPP or a commercially available flurbiprofen (FP) gel-type patch. Study 1: The plasma concentration of SFP was sustained during 24-h topical application of the SFPP, showing a high percutaneous absorption ratio of 51.4-72.2 %. Cmax and AUC0-∞ were dose-proportional. Study 2: After application of the SFPP for 12 h, SFP concentrations in the synovial tissue and synovial fluid were 14.8-fold (p = 0.002) and 32.7-fold (p < 0.001) higher, respectively, than those achieved by the FP patch. Sustained plasma concentration of SFP and high percutaneous absorption ratio was observed after 24-h topical application of the SFPP. Compared to the FP patch, the SFPP showed superior percutaneous absorption and greater tissue penetration of SFP into the synovial tissue. Greater tissue penetration of the SFPP seemed to be primarily due to its formulation. Thus, SFPP is expected to show higher efficacy for the treatment of knee OA.

  13. Reconstructing Organophosphorus Pesticide Doses Using the Reversed Dosimetry Approach in a Simple Physiologically-Based Pharmacokinetic Model

    Directory of Open Access Journals (Sweden)

    Chensheng Lu

    2012-01-01

    Full Text Available We illustrated the development of a simple pharmacokinetic (SPK model aiming to estimate the absorbed chlorpyrifos doses using urinary biomarker data, 3,5,6-trichlorpyridinol as the model input. The effectiveness of the SPK model in the pesticide risk assessment was evaluated by comparing dose estimates using different urinary composite data. The dose estimates resulting from the first morning voids appeared to be lower than but not significantly different to those using before bedtime, lunch or dinner voids. We found similar trend for dose estimates using three different urinary composite data. However, the dose estimates using the SPK model for individual children were significantly higher than those from the conventional physiologically based pharmacokinetic (PBPK modeling using aggregate environmental measurements of chlorpyrifos as the model inputs. The use of urinary data in the SPK model intuitively provided a plausible alternative to the conventional PBPK model in reconstructing the absorbed chlorpyrifos dose.

  14. Prediction of interindividual variation in drug plasma levels in vivo from individual enzyme kinetic data and physiologically based pharmacokinetic modeling

    NARCIS (Netherlands)

    Bogaards, J.J.P.; Hissink, E.M.; Briggs, M.; Weaver, R.; Jochemsen, R.; Jackson, P.; Bertrand, M.; Bladeren, P. van

    2000-01-01

    A strategy is presented to predict interindividual variation in drug plasma levels in vivo by the use of physiologically based pharmacokinetic modeling and human in vitro metabolic parameters, obtained through the combined use of microsomes containing single cytochrome P450 enzymes and a human liver

  15. Pharmacokinetics and pharmacodynamic effects of amiodarone in plasma of ponies after single intravenous administration

    International Nuclear Information System (INIS)

    Trachsel, D.; Tschudi, P.; Portier, C.J.; Kuhn, M.; Thormann, W.; Scholtysik, G.; Mevissen, M.

    2004-01-01

    Atrial fibrillation is a well-known heart disease in horses. The common therapy consists of administration of quinidine. More potent antiarrhythmic drugs have become available for human therapy and the use of these as alternatives to quinidine for equine antiarrhythmic therapy is a matter of interest. Amiodarone (AMD) is used in human medicine for treatment of many arrhythmias, including atrial fibrillation. Its disposition in horses has not yet been investigated. The purpose of this study was to measure the effect of single intravenous doses of amiodarone (5 and 7 mg/kg) on the surface electrocardiogram (ECG) of healthy minishetland ponies during the first 2 days after drug administration and to calculate pharmacokinetic parameters with a physiologically based pharmacokinetic model (PBPK) using amiodarone and desethylamiodarone (DAMD) plasma levels that were determined by high-performance liquid chromatography (HPLC). As expected for a K + -channel-blocker, the main effect on the measured ECG could be seen on the ventricular complex, as the QT interval and the T wave showed statistically significant alterations. The doses investigated were well tolerated clinically. Results from the pharmacokinetic model were found to compare well with literature data of rats, dogs, and humans. It showed a rapid distribution in the tissue, beginning with the rapidly perfused tissue, like the heart, followed by slowly perfused tissues, and finally an accumulation in fat. The half-life for total elimination was calculated to be 16.3 days with 99% eliminated by 97 days. The model predicts that approximately 96% of amiodarone is eliminated as desethylamiodarone in urine, 2% eliminated as desethylamiodarone in bile, and 2% as other metabolites

  16. Human pharmacokinetics, biodistribution and dosimetry of 99m Tc labelled monoclonal antibody ior egf/r3 in patients with tumors of epithelial origin: preliminary results

    International Nuclear Information System (INIS)

    Iznaga-Escobar, Normando E.; Morales, Alejo; Ramos, Mayra; Perez, Niuvis; Torres, Leonel A.; Alavarez, Ivette; Rodriguez, Nelson; Fraxedas, Roberto; Rodriguez, Oscar; Stabin, Michael G.

    1997-01-01

    Human pharmacokinetics, biodistribution and internal radiation dosimetry to normal organs and total body of 99m Tc-labeled monoclonal antibody ior egf/r 3 was investigated following intravenous injection in 5 patients. Following administration, blood and urine samples were collected from 4 patients up to 24 hr after injection Pharmacokinetics obtained from whole blood radioactivity showed blood disappearance described most properly by a biexponential model with a mean distribution half-life value of 0.14±0.02 hr and elimination half-life value of 31.0±13.6 hr. Whole body anterior and posterior scans were obtained at 10 min, 1,3,5 and 24 hr after injection. ROIs were drawn over the heart, liver spleen and bladder to measure the activity in the source organs. Time-activity curves for each source organ were fitted to mono- or biexponential functions by non-linear least squares regression using the flexible polyhedral method and integrated to determine organ residence times. The mean absorbed dose to the whole body and various normal organs were then estimated from residence times and from blood and urine samples using the MIRD method. The effective dose equivalent (EDE) and effective dose (ED) were calculated. Estimates of radiation absorbed dose to normal organs in rads/mCi administered (mean ± SD, n=4) were: whole body, 0.0185± 0.0023, gallbladder wall, 0.0755± 0.00761, spleen, 0.0637± 0.0167 and liver, 0.276± 0.029. The effective dose equivalent and effective dose estimates for adults were 0.039± 0.008 and 0.028± 0.004 rem/m Ci administered. (author). 15 refs., 3 figs., 3 tabs

  17. Human pharmacokinetics, biodistribution and dosimetry of {sup 99m} Tc labelled monoclonal antibody ior egf/r3 in patients with tumors of epithelial origin: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Iznaga-Escobar, Normando E.; Morales, Alejo; Ramos, Mayra; Perez, Niuvis [Center of Molecular Immunology (CIM), Havana (Cuba); Torres, Leonel A.; Alavarez, Ivette [Center of Clinical Researches (CIC), Havana (Cuba); Rodriguez, Nelson [Center of Medical-Surgical Researches (CIMEQ), Havana (Cuba); Fraxedas, Roberto [Institute of Nephrology (INEF), Havana (Cuba); Rodriguez, Oscar [Orthopedic Hospital Frank Pais, Havana (Cuba); Stabin, Michael G. [Radiation Internal Dose Information Center (RIDIC), Oak Ridge, TN (United States)

    1997-12-01

    Human pharmacokinetics, biodistribution and internal radiation dosimetry to normal organs and total body of {sup 99m} Tc-labeled monoclonal antibody ior egf/r{sup 3} was investigated following intravenous injection in 5 patients. Following administration, blood and urine samples were collected from 4 patients up to 24 hr after injection Pharmacokinetics obtained from whole blood radioactivity showed blood disappearance described most properly by a biexponential model with a mean distribution half-life value of 0.14{+-}0.02 hr and elimination half-life value of 31.0{+-}13.6 hr. Whole body anterior and posterior scans were obtained at 10 min, 1,3,5 and 24 hr after injection. ROIs were drawn over the heart, liver spleen and bladder to measure the activity in the source organs. Time-activity curves for each source organ were fitted to mono- or biexponential functions by non-linear least squares regression using the flexible polyhedral method and integrated to determine organ residence times. The mean absorbed dose to the whole body and various normal organs were then estimated from residence times and from blood and urine samples using the MIRD method. The effective dose equivalent (EDE) and effective dose (ED) were calculated. Estimates of radiation absorbed dose to normal organs in rads/mCi administered (mean {+-} SD, n=4) were: whole body, 0.0185{+-} 0.0023, gallbladder wall, 0.0755{+-} 0.00761, spleen, 0.0637{+-} 0.0167 and liver, 0.276{+-} 0.029. The effective dose equivalent and effective dose estimates for adults were 0.039{+-} 0.008 and 0.028{+-} 0.004 rem/m Ci administered. (author). 15 refs., 3 figs., 3 tabs.

  18. Development of a simple chromatographic method for the determination of piracetam in human plasma and its pharmacokinetic evaluation.

    Science.gov (United States)

    Barkat, K; Ahmad, M; Minhas, M U; Malik, M Z; Sohail, M

    2014-07-01

    The objective of study was to develop an accurate and reproducible HPLC method for determination of piracetam in human plasma and to evaluate pharmacokinetic parameters of 800 mg piracetam. A simple, rapid, accurate, precise and sensitive high pressure liquid chromatography method has been developed and subsequently validated for determination of piracetam. This study represents the results of a randomized, single-dose and single-period in 18 healthy male volunteers to assess pharmacokinetic parameters of 800 mg piracetam tablets. Various pharmacokinetic parameters were determined from plasma for piracetam and found to be in good agreement with previous reported values. The data was analyzed by using Kinetica® version 4.4 according to non-compartment model of pharmacokinetic analysis and after comparison with previous studies, no significant differences were found in present study of tested product. The major pharmacokinetic parameters for piracetam were as follows: t1/2 was (4.40 ± 0.179) h; Tmax value was (2.33 ± 0.105) h; Cmax was (14.53 ± 0.282) µg/mL; the AUC(0-∞) was (59.19 ± 4.402) µg · h/mL. AUMC(0-∞) was (367.23 ± 38.96) µg. (h)(2)/mL; Ke was (0.16 ± 0.006) h; MRT was (5.80 ± 0.227) h; Vd was (96.36 ± 8.917 L). A rapid, accurate and precise high pressure liquid chromatography method was developed and validated before the study. It is concluded that this method is very useful for the analysis of pharmacokinetic parameters, in human plasma and assured the safety and efficacy of piracetam, can be effectively used in medical practice. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women.

    Science.gov (United States)

    Mutagonda, Ritah F; Kamuhabwa, Appolinary A R; Minzi, Omary M S; Massawe, Siriel N; Asghar, Muhammad; Homann, Manijeh V; Färnert, Anna; Aklillu, Eleni

    2017-07-03

    Pregnancy has considerable effects on the pharmacokinetic properties of drugs used to treat uncomplicated Plasmodium falciparum malaria. The role of pharmacogenetic variation on anti-malarial drug disposition and efficacy during pregnancy is not well investigated. The study aimed to examine the effect of pharmacogenetics on lumefantrine (LF) pharmacokinetics and treatment outcome in pregnant women. Pregnant women with uncomplicated falciparum malaria were enrolled and treated with artemether-lumefantrine (ALu) at Mkuranga and Kisarawe district hospitals in Coast Region of Tanzania. Day-7 LF plasma concentration and genotyping forCYP2B6 (c.516G>T, c.983T>C), CYP3A4*1B, CYP3A5 (*3, *6, *7) and ABCB1 c.4036A4G were determined. Blood smear for parasite quantification by microscopy, and dried blood spot for parasite screening and genotyping using qPCR and nested PCR were collected at enrolment up to day 28 to differentiate between reinfection from recrudescence. Treatment response was recorded following the WHO protocol. In total, 92 pregnant women in their second and third trimester were included in the study and 424 samples were screened for presence of P. falciparum. Parasites were detected during the follow up period in 11 (12%) women between day 7 and 28 after treatment and PCR genotyping confirmed recrudescent infection in 7 (63.3%) women. The remaining four (36.4%) pregnant women had reinfection: one on day 14 and three on day 28. The overall PCR-corrected treatment failure rate was 9.0% (95% CI 4.4-17.4). Day 7 LF concentration was not significantly influenced by CYP2B6, CYP3A4*1B and ABCB1 c.4036A>G genotypes. Significant associations between CYP3A5 genotype and day 7 plasma LF concentrations was found, being higher in carriers of CYP3A5 defective variant alleles than CYP3A5*1/*1 genotype. No significant influence of CYP2B6, CYP3A5 and ABCB1 c.4036A>Genotypes on malaria treatment outcome were observed. However, CYP3A4*1B did affect malaria treatment outcome in

  20. Pooled population pharmacokinetic model of imipenem in plasma and the lung epithelial lining fluid.

    Science.gov (United States)

    van Hasselt, J G Coen; Rizk, Matthew L; Lala, Mallika; Chavez-Eng, Cynthia; Visser, Sandra A G; Kerbusch, Thomas; Danhof, Meindert; Rao, Gauri; van der Graaf, Piet H

    2016-06-01

    Several clinical trials have confirmed the therapeutic benefit of imipenem for treatment of lung infections. There is however no knowledge of the penetration of imipenem into the lung epithelial lining fluid (ELF), the site of action relevant for lung infections. Furthermore, although the plasma pharmacokinetics (PK) of imipenem has been widely studied, most studies have been based on selected patient groups. The aim of this analysis was to characterize imipenem plasma PK across populations and to quantify imipenem ELF penetration. A population model for imipenem plasma PK was developed using data obtained from healthy volunteers, elderly subjects and subjects with renal impairment, in order to identify predictors for inter-individual variability (IIV) of imipenem PK. Subsequently, a clinical study which measured plasma and ELF concentrations of imipenem was included in order to quantify lung penetration. A two compartmental model best described the plasma PK of imipenem. Creatinine clearance and body weight were included as subject characteristics predictive for IIV on clearance. Typical estimates for clearance, central and peripheral volume, and inter-compartmental clearance were 11.5 l h(-1) , 9.37 l, 6.41 l, 13.7 l h(-1) , respectively (relative standard error (RSE) imipenem into ELF was described using a time-independent penetration coefficient of 0.44 (RSE 14%). The identified lung penetration coefficient confirms the clinical relevance of imipenem for treatment of lung infections, while the population PK model provided insights into predictors of IIV for imipenem PK and may be of relevance to support dose optimization in various subject groups. © 2016 The British Pharmacological Society.

  1. Effect of cortex mori on pharmacokinetic profiles of main isoflavonoids from pueraria lobata in rat plasma.

    Science.gov (United States)

    Xiao, Bingxin; Sun, Zengxian; Sun, Shu Yang; Dong, Jie; Li, Yanli; Gao, Shan; Pang, Jie; Chang, Qi

    2017-09-14

    Radix pueraria (the root of pueraria lobata (Wild.) Ohwi.), which contains a class of isoflavonoids as the main active components, as well as cortex mori (the root bark of Morus alba L), which contains abundant active alkaloids, have been employed for the treatment of diabetes in traditional Chinese medicine for centuries. In previous studies, pharmacodynamic synergistic reactions have been observed in compatible application of pueraria lobata isoflavonoids extracts (PLF) and cortex mori alkaloids extracts (CME) for inhibiting α-glycosidase activity. It has also been demonstrated that PLF can effectively slow down the absorption of active alkaloid from CME, so as to produce a higher effective concentration in small intestine for depressing the elevation of postprandial blood glucose through inhibiting α-glycosidase activity. In this study, the hypoglycemic effect of PLF, CME or CME-PLF mixture (the mixture of CME and PLF at a ratio of 1:6.3) was further evaluated through in vivo glucose tolerance studies. And the effect of CME on pharmacokinetic profiles of main isoflavonoids from PLF in rat plasma was investigated to further underlie compatibility mechanism of the two herbs. Four groups of rats received an oral dose of starch solution alone or simultaneously with drugs by gavage feeding. The blood samples were collected to determine glucose concentrations by glucose oxidase method. In addition, another two groups of rats were orally administered with PLF or CME-PLF. The plasma samples were collected and assayed using an LC/MS/MS method for comparatively pharmacokinetic studies of five main isoflavonoids. For starch loading, co-administration of CME-PLF resulted in more potent inhibition effects on glucose responses compared to those by CME or PLF in rat. The isoflavonoids from PLF were rapidly absorbed, presenting similarly low concentrations in plasma. When CME was added, the C max and AUC of all the five isoflavonoids were increased. A phenomenon of double

  2. Pharmacokinetic studies of bergapten in dog plasma by using a LC-MS/MS method studies.

    Science.gov (United States)

    Gao, Y; Liu, Y Z; Zhang, X-M; Zhou, Y; Zhang, X; Dong, C-Y

    2013-07-01

    A sensitive LC-MS/MS method was developed for the determination of bergapten in dog plasma. The chromatographic separation was carried out on a Hypersil ODS column with a mobile phase consisting of methanol-water. The plasma sample was precipitated with methanol and prepare for injecting onto the LC-MS/MS system. The detection was performed on a triple quadrupole tandem mass spectrometer by MRM via electro spray ionization source. The standard curve for bergapten was linear over the concentration range of 0.5-500 ng/mL with a lower limit of quantification of 0.5 ng/mL. The inter-day and intra-day precision (R.S.D.%) for bergapten varied between 3.4 and 11.5. The corresponding inter-day and intra-day accuracy (Bias%) ranged between -3.8 and 6.9. For the pharmacokinetic analysis of serum, the mean (SD) values obtained for the bergapten were as follows: Cmax, 228.5 (14.3) ng/ml; Tmax, 4.2 (0.4) h; t1/2, 6.9 (2.3) h; AUC0-t h, 2507.2 (168.5) ng · h/mL and AUC0-∞, 3 219.2 (211.4) ng · h/mL, respectively. © Georg Thieme Verlag KG Stuttgart · New York.

  3. Determination and pharmacokinetic studies of arecoline in dog plasma by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Li, Bing; Zhou, Xu-Zheng; Li, Jian-Yong; Yang, Ya-Jun; Niu, Jian-Rong; Wei, Xiao-Juan; Liu, Xi-Wang; Li, Jin-Shan; Zhang, Ji-Yu

    2014-10-15

    A rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of arecoline concentration in dog plasma. Plasma sample was prepared by protein precipitation using n-hexane (containing 1% isoamyl alcohol) with β-pinene as an internal standard. Chromatographic separation was achieved on an Agilent C18 column (4.6×75mm, 3.5μm) using methanol: 5mM ammonium acetate as the mobile phase with isocratic elution. Mass detection was carried out using positive electrospray ionization in multiple reaction monitoring mode. The calibration curve for arecoline was linear over a concentration range of 2-500ng/mL. The intra-day and inter-day accuracy and precision were within the acceptable limits of ±10% at all concentrations. In summary, the LC-MS/MS method described herein was fully validated and successfully applied to the pharmacokinetic study of arecoline hydrobromide tablets in dogs after oral administration. Copyright © 2014. Published by Elsevier B.V.

  4. Milk decreases urinary excretion but not plasma pharmacokinetics of cocoa flavan-3-ol metabolites in humans.

    Science.gov (United States)

    Mullen, William; Borges, Gina; Donovan, Jennifer L; Edwards, Christine A; Serafini, Mauro; Lean, Michael E J; Crozier, Alan

    2009-06-01

    Cocoa drinks containing flavan-3-ols are associated with many health benefits, and conflicting evidence exists as to whether milk adversely affects the bioavailability of flavan-3-ols. The objective was to determine the effect of milk on the bioavailability of cocoa flavan-3-ol metabolites. Nine human volunteers followed a low-flavonoid diet for 2 d before drinking 250 mL of a cocoa beverage, made with water or milk, that contained 45 micromol (-)-epicatechin and (-)-catechin. Plasma and urine samples were collected for 24 h, and flavan-3-ol metabolites were analyzed by HPLC with photodiode array and mass spectrometric detection. Milk affected neither gastric emptying nor the transit time through the small intestine. Two flavan-3-ol metabolites were detected in plasma and 4 in urine. Milk had only minor effects on the plasma pharmacokinetics of an (epi)catechin-O-sulfate and had no effect on an O-methyl-(epi)catechin-O-sulfate. However, milk significantly lowered the excretion of 4 urinary flavan-3-ol metabolites from 18.3% to 10.5% of the ingested dose (P = 0.016). Studies that showed protective effects of cocoa and those that showed no effect of milk on bioavailability used products that have a much higher flavan-3-ol content than does the commercial cocoa used in the present study. Most studies of the protective effects of cocoa have used drinks with a very high flavan-3-ol content. Whether similar protective effects are associated with the consumption of many commercial chocolate and cocoa products containing substantially lower amounts of flavan-3-ols, especially when absorption at lower doses is obstructed by milk, remains to be determined.

  5. Pharmacokinetics and Dosimetry Studies for Optimization of Pretargeted Radioimmunotherapy in CEA-Expressing Advanced Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Caroline eBodet-Milin

    2015-11-01

    Full Text Available Objectives. A phase I pretargeted radioimmunotherapy trial (EudractCT 200800603096 was designed in patients with metastatic lung cancer expressing carcinoembryonic antigen (CEA to optimize bispecific antibody and labelled peptide doses, as well as the delay between their injections.Methods. Three cohorts of 3 patients received the anti-CEA x anti-histamine-succinyl-glycine (HSG humanized trivalent bispecific antibody (TF2 and the IMP288 bivalent HSG-peptide. Patients underwent a pre-therapeutic imaging session S1 (44 or 88 nmol/m2 of TF2 followed by 4.4 nmol/m2, 185 MBq, of 111In-labelled IMP288, and, 1-2 weeks later, a therapy session S2 (240 or 480 nmol/m2 of TF2 followed by 24 nmol/m2, 1.1 GBq/m2, 177Lu-labeled IMP288. The pretargeting delay was 24 or 48 hours. The dose schedule was defined based on pre-clinical TF2 pharmacokinetic studies, on our previous clinical data using the previous anti-CEA pretargeting system and on clinical results observed in the first patients injected using the same system in the Netherlands.Results. TF2 pharmacokinetics (PK was represented by a two-compartment model in which the central compartment volume was linearly dependent on the patient's surface area. PK were remarkably similar, with a clearance of 0.33 +/- 0.03 L/h per m2. 111In- and 177Lu-IMP288 PK were also well represented by a two-compartment model. IMP288 PK were faster (clearance 1.4 to 3.3 l/h. The central compartment volume was proportional to body surface area and IMP288clearance depended on the molar ratio of injected IMP288 to circulating TF2 at the time of IMP288 injection. Modelling of image quantification confirmed the dependence of IMP288 kinetics on circulating TF2, but tumour activity PK were variable. Organ absorbed doses were not significantly different in the 3 cohorts, but the tumour dose was significantly higher with the higher molar doses of TF2 (p < 0.002. S1 imaging predicted absorbed doses calculated in S2. Conclusion. The best

  6. Effect of a single gemfibrozil dose on the pharmacokinetics of rosuvastatin in bile and plasma in healthy volunteers.

    Science.gov (United States)

    Bergman, Ebba; Matsson, Elin M; Hedeland, Mikael; Bondesson, Ulf; Knutson, Lars; Lennernäs, Hans

    2010-09-01

    The effect of a single intrajejunal dose of gemfibrozil (600 mg) on the plasma pharmacokinetics and biliary excretion of a single intrajejunal dose of rosuvastatin (20 mg) was investigated by using a multichannel catheter positioned in the distal duodenum-proximal jejunum in 8 healthy volunteers. Bile and plasma samples were collected every 20 minutes for 200 minutes, with additional plasma samples being drawn for up to 48 hours. Gemfibrozil did not affect the bioavailability of rosuvastatin, although it increased the apparent absorption phase during the initial 200 minutes (AUC(plasma,200min)) by 1.56-fold (95% confidence interval, 1.14-2.15). The interaction was less pronounced in this single-dose study than in a previous report when gemfibrozil was administered repeatedly; nevertheless, the interaction coincided with the highest exposure to gemfibrozil. The plausible reason why the interaction in this investigation was only minor is the low exposure to gemfibrozil (and its metabolites), suggesting that the total plasma concentration of gemfibrozil needs to be above 20 µM to affect the disposition of rosuvastatin. This study demonstrates the value of monitoring the plasma pharmacokinetics of the inhibitor, and not only the drug under investigation, to improve the mechanistic interpretation.

  7. Metabolic profiles of pomalidomide in human plasma simulated with pharmacokinetic data in control and humanized-liver mice.

    Science.gov (United States)

    Shimizu, Makiko; Suemizu, Hiroshi; Mitsui, Marina; Shibata, Norio; Guengerich, F Peter; Yamazaki, Hiroshi

    2017-10-01

    1. Pomalidomide has been shown to be potentially teratogenic in thalidomide-sensitive animal species such as rabbits. Screening for thalidomide analogs devoid of teratogenicity/toxicity - attributable to metabolites formed by cytochrome P450 enzymes - but having immunomodulatory properties is a strategic pathway towards development of new anticancer drugs. 2. In this study, plasma concentrations of pomalidomide, its primary 5-hydroxylated metabolite, and its glucuronide conjugate(s) were investigated in control and humanized-liver mice. Following oral administration of pomalidomide (100 mg/kg), plasma concentrations of 7-hydroxypomalidomide and 5-hydroxypomalidomide glucuronide were slightly higher in humanized-liver mice than in control mice. 3. Simulations of human plasma concentrations of pomalidomide were achieved with simplified physiologically-based pharmacokinetic models in both groups of mice in accordance with reported pomalidomide concentrations after low dose administration in humans. 4. The results indicate that pharmacokinetic profiles of pomalidomide were roughly similar between control mice and humanized-liver mice and that control and humanized-liver mice mediated pomalidomide 5-hydroxylation in vivo. Introducing one aromatic amino group into thalidomide resulted in less species differences in in vivo pharmacokinetics in control and humanized-liver mice.

  8. Determination of piracetam in rat plasma by LC-MS/MS and its application to pharmacokinetics.

    Science.gov (United States)

    Wang, Xianqin; Zhu, Jiayin; Xu, Renai; Yang, Xuezhi; Wu, Haiya; Lin, Dan; Ye, Faqing; Hu, Lufeng

    2010-10-01

    A sensitive and selective liquid chromatography-tandem mass spectrometry method for the determination of piracetam in rat plasma was developed and validated over the concentration range of 0.1-20 µg/mL. After addition of oxiracetam as internal standard, a simplified protein precipitation with trichloroacetic acid (5%) was employed for the sample preparation. Chromatographic separation was performed by a Zorbax SB-Aq column (150 × 2.1 mm, 3.5 µm). The mobile phase was acetonitrile-1% formic acid in water (10:90 v/v) delivered at a flow rate of 0.3 mL/min. The MS data acquisition was accomplished in multiple reaction monitoring mode with a positive electrospray ionization interface. The lower limit of quantification was 0.1 µg/mL. For inter-day and intra-day tests, the precision (RSD) for the entire validation was less than 9%, and the accuracy was within the 94.6-103.2% range. The developed method was successfully applied to pharmacokinetic studies of piracetam in rats following single oral administration dose of 50 mg/kg. Copyright © 2010 John Wiley & Sons, Ltd.

  9. Plasma pharmacokinetics after combined therapy of gemcitabine and oral S-1 for unresectable pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Okita Yoshihiro

    2010-02-01

    Full Text Available Abstract Background The combination of gemcitabine (GEM and S-1, an oral 5-fluorouracil (5-FU derivative, has been shown to be a promising regimen for patients with unresectable pancreatic cancer. Methods Six patients with advanced pancreatic cancer were enrolled in this pharmacokinetics (PK study. These patients were treated by oral administration of S-1 30 mg/m2 twice daily for 28 consecutive days, followed by a 14-day rest period and intravenous administration of GEM 800 mg/m2 on days 1, 15 and 29 of each course. The PK parameters of GEM and/or 5-FU after GEM single-administration, S-1 single-administration, and co-administration of GEM with pre-administration of S-1 at 2-h intervals were analyzed. Results The maximum concentration (Cmax, the area under the curve from the drug administration to the infinite time (AUCinf, and the elimination half-life (T1/2 of GEM were not significantly different between GEM administration with and without S-1. The Cmax, AUCinf, T1/2, and the time required to reach Cmax (Tmax were not significantly different between S-1 administration with and without GEM. Conclusion There were no interactions between GEM and S-1 regarding plasma PK of GEM and 5-FU.

  10. Pharmacokinetics of betamethasone in plasma, urine, and synovial fluid following intra-articular administration to exercised thoroughbred horses.

    Science.gov (United States)

    Knych, Heather K; Stanley, Scott D; Harrison, Linda M; Mckemie, Daniel S

    2017-09-01

    The use of corticosteroids, such as betamethasone, in performance horses is tightly regulated. The objective of the current study was to describe the plasma pharmacokinetics of betamethasone as well as time-related urine and synovial fluid concentrations following intra-articular administration to horses. Twelve racing-fit adult Thoroughbred horses received a single intra-articular administration (9 mg) of a betamethasone sodium phosphate and betamethasone acetate injectable suspension into the right antebrachiocarpal joint. Blood, urine, and synovial fluid samples were collected prior to and at various times up to 21 days post drug administration. All samples were analyzed using tandem liquid chromatography-mass spectrometry. Plasma data were analyzed using compartmental pharmacokinetic modeling. Maximum measured plasma betamethasone concentrations were 3.97 ± 0.23 ng/mL at 1.45 ± 0.20 h. The plasma elimination half-life was 7.48 ± 0.39 h. Betamethasone concentrations were below the limit of detection in all horses by 96 h and 7 days in plasma and urine, respectively. Betamethasone fell below the limit of detection in the right antebrachiocarpal joint between 14 and 21 days. Results of this study provide information that can be used to regulate the use of intra-articular betamethasone in the horse. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Population pharmacokinetics of piperacillin in the early phase of septic shock: does standard dosing result in therapeutic plasma concentrations?

    Science.gov (United States)

    Öbrink-Hansen, Kristina; Juul, Rasmus Vestergaard; Storgaard, Merete; Thomsen, Marianne Kragh; Hardlei, Tore Forsingdal; Brock, Birgitte; Kreilgaard, Mads; Gjedsted, Jakob

    2015-11-01

    Antibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic (PK) variability seen in this patient population. Piperacillin-tazobactam is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality. Accordingly, we determined the pharmacokinetic profile of piperacillin (4 g) every 8 h, during the third consecutive dosing interval, in 15 patients treated empirically for septic shock. We developed a population pharmacokinetic model to assess empirical dosing and to simulate alternative dosing regimens and modes of administration. Time above the MIC (T>MIC) predicted for each patient was evaluated against clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter). Pharmacokinetic-pharmacodynamic (PK/PD) targets evaluated were 50% fT>4×MIC and 100% fT>MIC. A population PK model was developed using NONMEM, and data were best described by a two-compartment model. Central and intercompartmental clearances were 3.6 liters/h (relative standard error [RSE], 15.7%) and 6.58 liters/h (RSE, 16.4%), respectively, and central and peripheral volumes were 7.3 liters (RSE, 11.8%) and 3.9 liters (RSE, 9.7%), respectively. Piperacillin plasma concentrations varied considerably between patients and were associated with levels of plasma creatinine. Patients with impaired renal function were more likely to achieve predefined PK/PD targets than were patients with preserved or augmented renal function. Simulations of alternative dosing regimens showed that frequent intermittent bolus dosing as well as dosing by extended and continuous infusion increases the probability of attaining therapeutic plasma concentrations. For septic shock patients with preserved or augmented renal function, dose increment or prolonged infusion of the drug needs to be considered. (This study has been registered at ClinicalTrials.gov under registration no. NCT02306928.). Copyright © 2015, American Society for Microbiology

  12. Plasma Pharmacokinetics of Polyphenols in a Traditional Japanese Medicine, Jumihaidokuto, Which Suppresses Propionibacterium acnes-Induced Dermatitis in Rats

    Directory of Open Access Journals (Sweden)

    Takashi Matsumoto

    2015-09-01

    Full Text Available Most orally administered polyphenols are metabolized, with very little absorbed as aglycones and/or unchanged forms. Metabolic and pharmacokinetic studies are therefore necessary to understand the pharmacological mechanisms of polyphenols. Jumihaidokuto (JHT, a traditional Japanese medicine, has been used for treatment of skin diseases including inflammatory acne. Because JHT contains various types of bioactive polyphenols, our aim was to clarify the metabolism and pharmacokinetics of the polyphenols in JHT and identify active metabolites contributing to its antidermatitis effects. Orally administered JHT inhibited the increase in ear thickness in rats induced by intradermal injection of Propionibacterium acnes. Quantification by LC-MS/MS indicated that JHT contains various types of flavonoids and is also rich in hydrolysable tannins, such as 1,2,3,4,6-penta-O-galloyl glucose. Pharmacokinetic and antioxidant analyses showed that some flavonoid conjugates, such as genistein 7-O-glucuronide and liquiritigenin 7-O-glucuronide, appeared in rat plasma and had an activity to inhibit hydrogen peroxide-dependent oxidation. Furthermore, 4-O-methylgallic acid, a metabolite of Gallic acid, appeared in rat plasma and inhibited the nitric oxide reaction. JHT has numerous polyphenols; it inhibited dermatitis probably via the antioxidant effect of its metabolites. Our study is beneficial for understanding in vivo actions of orally administered polyphenol drugs.

  13. Use of plasma creatine kinase pharmacokinetics to estimate the amount of excercise-induced muscle damage in Beagles.

    Science.gov (United States)

    Chanoit, G P; Lefebvre, H P; Orcel, K; Laroute, V; Toutain, P L; Braun, J P

    2001-09-01

    To assess the effects of moderate exercise on plasma creatine kinase (CK) pharmacokinetics and to estimate exercise-induced muscle damage in dogs. 6 untrained adult Beagles. The study was divided into 3 phases. In phase 1, dogs ran for 1 hour at a speed of 9 km/h, and samples were used to determine the area under the plasma CK activity versus time curve (AUC) induced by exercise. In phases 2 and 3, pharmacokinetics of CK were calculated in dogs during exercise and at rest, respectively. Values for AUC and plasma clearance (CI) were used to estimate muscle damage. At rest, values for Cl, steady-state volume of distribution (Vdss), and mean retention time (MRT) were 0.32+/-0.02 ml/kg of body weight/min, 57+/-173 ml/kg, and 3.0+/-0.57 h, respectively. During exercise, Cl decreased significantly (0.26+/-0.03 ml/kg/min), MRT increased significantly, (4.4+/-0.97 h), and Vdss remained unchanged. Peak of plasma CK activity (151+/-58.8 U/L) was observed 3 hours after completion of exercise. Estimated equivalent amount of muscle corresponding to the quantity of CK released was 41+/-29.3 mg/kg. These results revealed that exercise had a minor effect on CK disposition and that the equivalent amount of muscle damaged by moderate exercise was negligible. This study illustrates the relevance for use of the minimally invasive and quantitative pharmacokinetic approach when estimating muscle damage.

  14. Dosimetry; La dosimetrie

    Energy Technology Data Exchange (ETDEWEB)

    Le Couteulx, I.; Apretna, D.; Beaugerie, M.F. [Electricite de France (EDF), 75 - Paris (France)] [and others

    2003-07-01

    Eight articles treat the dosimetry. Two articles evaluate the radiation doses in specific cases, dosimetry of patients in radiodiagnosis, three articles are devoted to detectors (neutrons and x and gamma radiations) and a computer code to build up the dosimetry of an accident due to an external exposure. (N.C.)

  15. A Population Pharmacokinetic Model for Disposition in Plasma, Saliva and Urine of Scopolamine after Intranasal Administration to Healthy Human Subjects

    Science.gov (United States)

    Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

    2014-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials with an Investigative New Drug (IND) protocol. The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trials with INSCOP. Methods: Twelve healthy human subjects were administered three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min and 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. Pharmacokinetic Compartmental models, using actual dosing and sampling times, were built using Phoenix (version 1.2). Model selection was based on the likelihood ratio test on the difference of criteria (-2LL) and comparison of the quality of fit plots. Results: The best structural model for INSCOP (minimal -2LL= 502.8) was established. It consisted of one compartment each for plasma, saliva and urine, respectively, which were connected with linear transport processes except the nonlinear PK process from plasma to saliva compartment. The best-fit estimates of PK parameters from individual PK compartmental analysis and Population PK model analysis were shown in Tables 1 and 2, respectively. Conclusion: A population PK model that could predict population and individual PK of scopolamine in plasma, saliva and urine after dosing was developed and validated. Incorporating a non-linear transfer from plasma to saliva compartments resulted in a significantly improved model fitting. The model could be used to predict scopolamine plasma concentrations from salivary and urinary drug levels, allowing non-invasive therapeutic monitoring of scopolamine in space and other remote environments.

  16. Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies.

    Science.gov (United States)

    Germovsek, Eva; Lutsar, Irja; Kipper, Karin; Karlsson, Mats O; Planche, Tim; Chazallon, Corine; Meyer, Laurence; Trafojer, Ursula M T; Metsvaht, Tuuli; Fournier, Isabelle; Sharland, Mike; Heath, Paul; Standing, Joseph F

    2018-04-19

    Sepsis and bacterial meningitis are major causes of mortality and morbidity in neonates and infants. Meropenem, a broad-spectrum antibiotic, is not licensed for use in neonates and infants below 3 months of age and sufficient information on its plasma and CSF disposition and dosing in neonates and infants is lacking. To determine plasma and CSF pharmacokinetics of meropenem in neonates and young infants and the link between pharmacokinetics and clinical outcomes in babies with late-onset sepsis (LOS). Data were collected in two recently conducted studies, i.e. NeoMero-1 (neonatal LOS) and NeoMero-2 (neonatal meningitis). Optimally timed plasma samples (n = 401) from 167 patients and opportunistic CSF samples (n = 78) from 56 patients were analysed. A one-compartment model with allometric scaling and fixed maturation gave adequate fit to both plasma and CSF data; the CL and volume (standardized to 70 kg) were 16.7 (95% CI 14.7, 18.9) L/h and 38.6 (95% CI 34.9, 43.4) L, respectively. CSF penetration was low (8%), but rose with increasing CSF protein, with 40% penetration predicted at a protein concentration of 6 g/L. Increased infusion time improved plasma target attainment, but lowered CSF concentrations. For 24 patients with culture-proven Gram-negative LOS, pharmacodynamic target attainment was similar regardless of the test-of-cure visit outcome. Simulations showed that longer infusions increase plasma PTA but decrease CSF PTA. CSF penetration is worsened with long infusions so increasing dose frequency to achieve therapeutic targets should be considered.

  17. The pharmacokinetic study of rutin in rat plasma based on an electrochemically reduced graphene oxide modified sensor

    Directory of Open Access Journals (Sweden)

    Pei Zhang

    2016-04-01

    Full Text Available An electrochemical method based on a directly electrochemically reduced graphene oxide (ERGO film coated on a glassy carbon electrode (GCE was developed for the rapid and convenient determination of rutin in plasma. ERGO was modified on the surface of GCE by one-step electro-deposition method. Electrochemical behavior of rutin on ERGO/GCE indicated that rutin underwent a surface-controlled quasi-reversible process and the electrochemical parameters such as charge transfer coefficient (α, electron transfer number (n and electrode reaction standard rate constant (ks were 0.53, 2 and 3.4 s−1, respectively. The electrochemical sensor for rutin in plasma provided a wide linear response range of 4.70×10−7−1.25×10−5 M with the detection limit (s/n=3 of 1.84×10−8 M. The assay was successfully used to the pharmacokinetic study of rutin. The pharmacokinetic parameters such as elimination rate half-life (t1/2, area under curve (AUC, and plasma clearance (CL were calculated to be 3.345±0.647 min, 5750±656.0 µg min/mL, and 5.891±0.458 mL/min/kg, respectively. The proposed method utilized a small sample volume of 10 μL and had no complicated sample pretreatment (without deproteinization, which was simple, eco-friendly, and time- and cost-efficient for rutin pharmacokinetic studies.

  18. Quantitative determination of metaxalone in human plasma by LC-MS and its application in a pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Lanting Zhao

    2016-10-01

    Full Text Available A simple and rapid method using liquid chromatography–mass spectrometry (LC-MS for the determination of metaxalone in human plasma has been developed and validated. Letrozole was used as the internal standard (IS. The plasma samples were simply treated with acetonitrile which allowed the precipitation of plasma proteins. The chromatographic separation was achieved on a Sapphire C18 (2.1 mm × 150 mm, 5 µm, Newark, USA column using the mobile phase (5 mM ammonium acetate containing 0.01% formic acid: acetonitrile (45:55, v/v at a flow rate of 0.3 ml/min. The selected ion monitoring (SIM in the positive mode was used for the determination of [M + H]+ m/z 222.1 and 286.1 for metaxalone and letrozole, respectively. The standard curve obtained was linear (r2 ≥ 0.99 over the concentration range of 30.24−5040 ng/ml. Meanwhile, no interfering peaks or matrix effect was observed. The method established was simple and successfully applied to a pharmacokinetic study of metaxalone in healthy Chinese volunteers after a single oral dose administration of 800 mg metaxalone. The main pharmacokinetic parameters of metaxalone were as follow: Cmax, (1664 ± 1208 ng/ml and (2063 ± 907 ng/ml; AUC0−36, (13925 ± 6590 ng/ml h and (18620 ± 5717 ng/ml h; t1/2, (13.6 ± 7.7 h and (20.3 ± 7.7 h for the reference and test tablets, respectively. These pharmacokinetic parameters of metaxalone in healthy Chinese volunteers were reported for the first time.

  19. GSK1265744 pharmacokinetics in plasma and tissue after single-dose long-acting injectable administration in healthy subjects.

    Science.gov (United States)

    Spreen, William; Ford, Susan L; Chen, Shuguang; Wilfret, David; Margolis, David; Gould, Elizabeth; Piscitelli, Stephen

    2014-12-15

    GSK1265744 (744) is an HIV-1 integrase inhibitor in clinical development as a long-acting (LA) injectable formulation. This study evaluated plasma and tissue pharmacokinetics after single-dose administration of 744 LA administered by intramuscular (IM) or subcutaneous injections. This was a phase I, open-label, 9-cohort, parallel study of 744 in healthy subjects. 744 was administered as a 200 mg/mL nanosuspension at doses of 100-800 mg IM and 100-400 mg subcutaneous. Eight (6 active and 2 placebo) male and female subjects participated in each of the first 7 cohorts. All 8 subjects, 4 males and 4 females, received active 744 LA in cohorts 8 and 9 and underwent rectal and cervicovaginal tissue sampling, respectively. Plasma pharmacokinetic sampling was performed for a minimum of 12 weeks or until 744 concentrations were ≤0.1 μg/mL. Rectal and cervicovaginal tissue biopsies were performed at weeks 2 and 8 (cohort 8) and weeks 4 and 12 (cohort 9). 744 LA was generally safe and well tolerated after single injections. A majority of subjects reported injection site reactions, all graded as mild in intensity. Plasma concentration-time profiles were prolonged with measureable concentrations up to 52 weeks after dosing. 744 LA 800 mg IM achieved mean concentrations above protein adjusted-IC90 for approximately 16 weeks. Rectal and cervicovaginal tissue concentrations ranged from injection has potential application as a monthly or less frequent HIV treatment or prevention agent.

  20. A phase 1 study of 131I-CLR1404 in patients with relapsed or refractory advanced solid tumors: dosimetry, biodistribution, pharmacokinetics, and safety.

    Directory of Open Access Journals (Sweden)

    Joseph J Grudzinski

    Full Text Available (131I-CLR1404 is a small molecule that combines a tumor-targeting moiety with a therapeutic radioisotope. The primary aim of this phase 1 study was to determine the administered radioactivity expected to deliver 400 mSv to the bone marrow. The secondary aims were to determine the pharmacokinetic (PK and safety profiles of (131I-CLR1404.Eight subjects with refractory or relapsed advanced solid tumors were treated with a single injection of 370 MBq of (131I-CLR1404. Whole body planar nuclear medicine scans were performed at 15-35 minutes, 4-6, 18-24, 48, 72, 144 hours, and 14 days post injection. Optional single photon emission computed tomography imaging was performed on two patients 6 days post injection. Clinical laboratory parameters were evaluated in blood and urine. Plasma PK was evaluated on (127I-CLR1404 mass measurements. To evaluate renal clearance of (131I-CLR1404, urine was collected for 14 days post injection. Absorbed dose estimates for target organs were determined using the RADAR method with OLINDA/EXM software.Single administrations of 370 MBq of (131I-CLR1404 were well tolerated by all subjects. No severe adverse events were reported and no adverse event was dose-limiting. Plasma (127I-CLR1404 concentrations declined in a bi-exponential manner with a mean t½ value of 822 hours. Mean Cmax and AUC(0-t values were 72.2 ng/mL and 15753 ng • hr/mL, respectively. An administered activity of approximately 740 MBq is predicted to deliver 400 mSv to marrow.Preliminary data suggest that (131I-CLR1404 is well tolerated and may have unique potential as an anti-cancer agent.ClinicalTrials.gov NCT00925275.

  1. Human plasma concentrations of tolbutamide and acetaminophen extrapolated from in vivo animal pharmacokinetics using in vitro human hepatic clearances and simple physiologically based pharmacokinetic modeling for radio-labeled microdose clinical studies

    International Nuclear Information System (INIS)

    Yamazaki, Hiroshi; Kunikane, Eriko; Nishiyama, Sayako; Murayama, Norie; Shimizu, Makiko; Sugiyama, Yuichi; Chiba, Koji; Ikeda, Toshihiko

    2015-01-01

    The aim of the current study was to extrapolate the pharmacokinetics of drug substances orally administered in humans from rat pharmacokinetic data using tolbutamide and acetaminophen as model compounds. Adjusted animal biomonitoring equivalents from rat studies based on reported plasma concentrations were scaled to human biomonitoring equivalents using known species allometric scaling factors. In this extrapolation, in vitro metabolic clearance data were obtained using liver preparations. Rates of tolbutamide elimination were roughly similar in rat and human liver microsome experiments, but acetaminophen elimination by rat liver microsomes and cytosolic preparations showed a tendency to be faster than those in humans. Using a simple physiologically based pharmacokinetic (PBPK) model, estimated human plasma concentrations of tolbutamide and acetaminophen were consistent with reported concentrations. Tolbutamide cleared in a roughly similar manner in humans and rats, but medical-dose levels of acetaminophen cleared (dependent on liver metabolism) more slowly from plasma in humans than it did in rats. The data presented here illustrate how pharmacokinetic data in combination with a simple PBPK model can be used to assist evaluations of the pharmacological/toxicological potential of new drug substances and for estimating human radiation exposures from radio-labeled drugs when planning human studies. (author)

  2. Using pharmacokinetic-pharmacodynamic modelling as a tool for prediction of therapeutic effective plasma levels of antipsychotics

    DEFF Research Database (Denmark)

    Olsen, Christina Kurre; Brennum, Lise Tøttrup; Kreilgaard, Mads

    2008-01-01

    response behaviour correlates well with the relationship between human dopamine D2 receptor occupancy and clinical effect. The aim of the present study was to evaluate how pharmacokinetic/pharmacodynamic (PK/PD) predictions of therapeutic effective steady-state plasma levels by means of conditioned...... the rat dopamine D2 receptor occupancy levels providing 50% response in the conditioned avoidance response test and the dopamine D2 receptor occupancy levels reported from responding schizophrenic patients treated with antipsychotics. Predictions of therapeutically effective steady-state levels...... for sertindole (+dehydrosertindole) and olanzapine were 3-4-fold too high whereas for haloperidol, clozapine and risperidone the predicted steady-state EC50 in conditioned avoidance responding rats correlated well with the therapeutically effective plasma levels observed in patients. Accordingly, the proposed PK...

  3. Rapid and Sensitive Determination of Timosaponin AIII in Rat Plasma by LC-MS/MS and Its Pharmacokinetic Application

    Directory of Open Access Journals (Sweden)

    Zhenzhen Cai

    2013-02-01

    Full Text Available A rapid sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS method was developed for determination of timosaponin AIII (TA-III in rat plasma, using ginsenoside Re as an internal standard (IS. TA-III and the IS were detected in MRM mode with a negative ionization electrospray mass spectrometer. The calibration curves were linear over the concentration ranges from 11.14 to 1114 ng/mL and the lower limit of quantification (LLOQ was 11.14 ng/mL. Intra-day and inter-day precisions (RSD were within 10%, and accuracy ranged from 6.4% to 9.1%. The extraction recovery at three concentrations ranged from 92.3% to 95.5%. The validated method was successfully applied to monitor the concentrations of TA-III in rat plasma after intragastric administration. The best fit pharmacokinetic model to estimate the pharmacokinetic parameters was a single compartment model with weight of 1/x2 for oral administration groups of rats for TA-III.

  4. Can Saliva and Plasma Methadone Concentrations Be Used for Enantioselective Pharmacokinetic and Pharmacodynamic Studies in Patients With Advanced Cancer?

    Science.gov (United States)

    George, Rani; Haywood, Alison; Good, Phillip; Hennig, Stefanie; Khan, Sohil; Norris, Ross; Hardy, Janet

    2017-09-01

    Methadone is a potent analgesic used to treat refractory cancer pain. It is administered as a racemic mixture, with the l-enantiomer being primarily a μ-receptor agonist, whereas the d-enantiomer is an N-methyl-d-aspartate antagonist and inhibits serotonin and norepinephrine reuptake. Dose requirements vary greatly among patients to achieve optimal pain control and to avoid the risk of adverse effects. The relationship between plasma and saliva methadone enantiomer concentrations was investigated to determine if saliva could be a substitute for plasma in pharmacodynamic and pharmacokinetic studies for clinical monitoring and dose optimization of methadone in patients with advanced cancer. Patients with advanced cancer who were prescribed varying doses of oral methadone for pain management were recruited to obtain paired plasma and saliva samples. Pain scores were recorded at the time of sampling. The total and unbound plasma and saliva concentrations of the l- and d-enantiomers of methadone were quantified by using an HPLC-MS/MS method. The relationship between plasma (total and unbound) and saliva concentrations were compared. The saliva-to-plasma concentration ratio was compared versus the dose administered and the time after dosing for both enantiomers. The association of methadone concentrations with reported pain scores was compared by using a Mann-Whitney U test for significance. Fifty patients receiving a mean dose of 11mg/d of methadone provided 151 paired plasma and saliva samples. The median age of the population was 61 years with an interquartile range of 53-71 years with total body weight ranging from 59-88 kg. Median (interquartile) total plasma concentrations for l- and d-methadone were 50.78 ng/mL (30.6-113.0 ng/mL) and 62.0 ng/mL (28.7-116.0 ng/mL), respectively. Median (interquartile range) saliva concentrations for l- and d-methadone were 81.5 ng/mL (28.0-203.2 ng/mL) and 44.2 (16.2-149.7 ng/mL). No relationship could be established between

  5. Plasma Pharmacokinetic and Heart Distribution Studies of Z-GP-EPI ...

    African Journals Online (AJOL)

    22, 44 µmol/kg) by intravenous injection and 70 mice (30 ... anticancer agents at the tumor site, where drug- converting ... at a temperature of 25 ± 2 °C and a relative humidity of 75 ± 5 ..... Jones G. Pharmacokinetics of vitamin D toxicity. Am J.

  6. Determination of antazoline hydrochloride in Beagle dog plasma by HPLC-UV and its application to pharmacokinetics.

    Science.gov (United States)

    Li, Xiaotian; Chu, Yanle; Ke, Yu; Wang, Linxi; Yu, Tong; Hao, Lianqi

    2013-06-15

    In order to evaluate the pharmacokinetics characteristic of antazoline hydrochloride in Beagle dogs, a sensitive and specific HPLC method was developed and validated using phenacetin as the internal standard (IS). The analyte and the IS were extracted from dog plasma by ethyl acetate under the basic condition. The analyte was separated by a C18 column and detected with a variable wavelength UV-detector. The mobile phase consisted of methanol-5mmolL(-1) tetrabutyl ammonium bromide (45:55, v/v) containing 0.5% glacial acetic acid in a flow rate of 1.0mLmin(-1). Standard calibration graph for antazoline was linear over a curve range of 20-1600ngmL(-1) (R>0.99) and the lower limit of quantification was 20ngmL(-1) using a plasma sample of 500μL. The intra- and inter-day precision values were less than 14.3% relative standard deviation (RSD). The intra-day assay accuracy was in the range of 98.1-100.6% and the inter-day assay accuracy in the range of 99.2-101.1%. The extraction recoveries were on the average of 88.4% for antazoline and 76.8% for IS. Plasma samples were stable at least for 1 month at -20°C. This method was successfully applied to pharmacokinetics study of antazoline after intravenous administration to Beagle dogs. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Ethanol-drug absorption interaction: potential for a significant effect on the plasma pharmacokinetics of ethanol vulnerable formulations.

    Science.gov (United States)

    Lennernäs, Hans

    2009-01-01

    Generally, gastric emptying of a drug to the small intestine is controlled by gastric motor activity and is the main factor affecting the onset of absorption. Accordingly, the emptying rate from the stomach is mainly affected by the digestive state, the properties of the pharmaceutical formulation and the effect of drugs, posture and circadian rhythm. Variability in the gastric emptying of drugs is reflected in variability in the absorption rate and the shape of the plasma pharmacokinetic profile. When ethanol interacts with an oral controlled release product, such that the mechanism controlling drug release is impaired, the delivery of the dissolved dose into the small intestine and the consequent absorption may result in dangerously high plasma concentrations. For example, the maximal plasma concentration of hydromorphone has individually been shown to be increased as much as 16 times through in vivo testing as a result of this specific pharmacokinetic ethanol-drug formulation interaction. Thus, a pharmacokinetic ethanol-drug interaction is a very serious safety concern when substantially the entire dose from a controlled release product is rapidly emptied into the small intestine (dose dumping), having been largely dissolved in a strong alcoholic beverage in the stomach during a sufficient lag-time in gastric emptying. Based on the literature, a two hour time frame for screening the in vitro dissolution profile of a controlled release product in ethanol concentrations of up to 40% is strongly supported and may be considered as the absolute minimum standard. It is also evident that the dilution, absorption and metabolism of ethanol in the stomach are processes with a minor effect on the local ethanol concentration and that ethanol exposure will be highly dependent on the volume and ethanol concentration of the fluid ingested, together with the rate of intake and gastric emptying. When and in which patients a clinically significant dose dumping will happen is

  8. Pharmacokinetic study of isatin in dog plasma by liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Ren, A; Wang, Q; Fang, Z; Gao, M; Wang, H; Zhang, J; Xu, W; Yue, W; Yin, L; Liu, Z; Li, X; Ding, B

    2015-12-01

    A sensitive and selective method was developed and validated to study the pharmacokinetics of isatin. The blood samples were pretreated by protein precipitation method using methanol. Quetiapine was used as an internal standard. After pretreatment, the samples were assayed by LC/MS/MS method and the pharmacokinetic parameters were calculated by WinNonlin 5.2 using non-compartment model. The separation was performed on a Venusil XBP PH column (5 µm, 2.0×100 mm) with an isocratic mobile phase consisted of methanol-water (containing 50 mM ammonium formate) (65:35, v/v) at a flow rate of 0.3 mL/min. The Agilent G6410B triple quadrupole LC/MS system was operated under the multiple reactions monitoring mode (MRM) using the electrospray ionization technique in positive mode. The lower limits of quantification (LLOQ) of the analyte of the method was 10 ng/mL. The method was linear with correlation coefficient >0.995. The intraday and interday accuracy and precision of the assay were acceptable. This method has been applied successfully to a pharmacokinetic study involving the oral and intravenous administration of isatin to beagle dogs.

  9. Determination of fenticonazole in human plasma by HPLC–MS/MS and its application to pharmacokinetic studies

    Directory of Open Access Journals (Sweden)

    Weixing Mao

    2017-02-01

    Full Text Available Two simple and sensitive high performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS methods were developed and validated for the determination of fenticonazole in human plasma after percutaneous and intravaginal administration. Mifepristone was used as an internal standard (IS, and simple protein precipitation by acetonitrile containing 2% acetic acid was utilized for extracting the analytes from the plasma samples. Chromatographic separation was performed on a Kinetex XB-C18 column. The quantitation was performed by a mass spectrometer equipped with an electrospray ionization source in multiple reactions monitoring (MRM positive ion mode using precursor-to-product ion transitions of m/z 455.2–199.1 for fenticonazole and m/z 430.2–372.3 for mifepristone. The validated linear ranges were 5–1000 pg/mL and 0.1–20 ng/mL fenticonazole in plasma for the methods A and B, respectively. For the two methods, the accuracy data ranged from 85% to 115%, the intra- and inter-batch precision data were less than 15%, the recovery data were more than 90%, and no matrix interference was observed. The methods A and B were successfully validated and applied to the pharmacokinetic studies of fenticonazole gel in Chinese healthy volunteers after percutaneous and intravaginal administration, respectively.

  10. Prediction of clearance, volume of distribution and half-life by allometric scaling and by use of plasma concentrations predicted from pharmacokinetic constants: a comparative study.

    Science.gov (United States)

    Mahmood, I

    1999-08-01

    Pharmacokinetic parameters (clearance, CL, volume of distribution in the central compartment, VdC, and elimination half-life, t1/2beta) predicted by an empirical allometric approach have been compared with parameters predicted from plasma concentrations calculated by use of the pharmacokinetic constants A, B, alpha and beta, where A and B are the intercepts on the Y axis of the plot of plasma concentration against time and alpha and beta are the rate constants, both pairs of constants being for the distribution and elimination phases, respectively. The pharmacokinetic parameters of cefpiramide, actisomide, troglitazone, procaterol, moxalactam and ciprofloxacin were scaled from animal data obtained from the literature. Three methods were used to generate plots for the prediction of clearance in man: dependence of clearance on body weight (simple allometric equation); dependence of the product of clearance and maximum life-span potential (MLP) on body weight; and dependence of the product of clearance and brain weight on body weight. Plasma concentrations of the drugs were predicted in man by use of A, B, alpha and beta obtained from animal data. The predicted plasma concentrations were then used to calculate CL, VdC and t1/2beta. The pharmacokinetic parameters predicted by use of both approaches were compared with measured values. The results indicate that simple allometry did not predict clearance satisfactorily for actisomide, troglitazone, procaterol and ciprofloxacin. Use of MLP or the product of clearance and brain weight improved the prediction of clearance for these four drugs. Except for troglitazone, VdC and t1/2beta predicted for man by use of the allometric approach were comparable with measured values for the drugs studied. CL, VdC and t1/2beta predicted by use of pharmacokinetic constants were comparable with values predicted by simple allometry. Thus, if simple allometry failed to predict clearance of a drug, so did the pharmacokinetic constant

  11. Liquid chromatography tandem mass spectrometry method for the estimation of lamotrigine in human plasma: Application to a pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Santosh Ghatol

    2013-04-01

    Full Text Available A reliable, selective and sensitive liquid chromatography tandem mass spectrometry method was developed and validated for the quantification of lamotrigine in human plasma using lamotrigine-13C3, d3 as an internal standard. Analyte and internal standard were extracted from human plasma by solid-phase extraction and detected in positive ion mode by tandem mass spectrometry with electrospray ionization (ESI interface. Chromatographic separation was performed on a Chromolith® SpeedROD; RP-18e column (50−4.6 mm i.d. using acetonitrile: 5±0.1 mM ammonium formate solution (90:10, v/v as the mobile phase at a flow rate of 0.500 mL/min. The calibration curves were linear over the range of 5.02–1226.47 ng/mL with the lower limit of quantitation validated at 5.02 ng/mL. The analytes were found stable in human plasma through three freeze (−20 °C-thaw (ice-cold water bath cycles and under storage on bench-top in ice-cold water bath for at least 6.8 h, and also in the mobile phase at 10 °C for at least 57 h. The method has shown good reproducibility, as the intra- and inter-day precisions were within 3.0%, while the accuracies were within ±6.0% of nominal values. The validated LC–MS/MS method was applied for the evaluation of pharmacokinetic and bioequivalence parameters of lamotrigine after an oral administration of 50 mg lamotrigine tablet to thirty-two healthy adult male volunteers. Keywords: Lamotrigine, Liquid chromatography/tandem mass spectrometry, Solid phase extraction, Pharmacokinetic study

  12. Pharmacokinetic Comparison of Berberine in Rat Plasma after Oral Administration of Berberine Hydrochloride in Normal and Post Inflammation Irritable Bowel Syndrome Rats

    Directory of Open Access Journals (Sweden)

    Zipeng Gong

    2014-01-01

    Full Text Available In the present study, post inflammation irritable bowel syndrome (PI-IBS rats were firstly established by intracolonic instillation of acetic acid with restraint stress. Then the pharmacokinetics of berberine in the rat plasma were compared after oral administration of berberine hydrochloride (25 mg/kg to normal rats and PI-IBS rats. Quantification of berberine in the rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 15 different points in time and the pharmacokinetic parameters were analyzed by WinNonlin software. Compared with the normal group, area under the plasma concentration vs. time curve from zero to last sampling time (AUC0–t and total body clearance (CL/F in the model group significantly increased or decreased, (2039.49 ± 492.24 vs. 2763.43 ± 203.14; 4999.34 ± 1198.79 vs. 3270.57 ± 58.32 respectively. The results indicated that the pharmacokinetic process of berberine could be altered in PI-IBS pathological conditions.

  13. Rapid Determination of Imatinib in Human Plasma by Liquid Chromatography-Tandem Mass Spectrometry: Application to a Pharmacokinetic Study

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jeong Soo; Cho, Eun Gi; Huh, Wooseong; Ko, Jaewook; Jung, Jin Ah; Lee, Sooyoun [Samsung Medical Center, Seoul (Korea, Republic of)

    2013-08-15

    A simple, fast and robust analytical method was developed to determine imatinib in human plasma using liquid chromatography-tandem mass spectrometry with electrospray ionization in the positive ion mode. Imatinib and labeled internal standard were extracted from plasma with a simple protein precipitation. The chromatographic separation was performed using an isocratic elution of mobile phase involving 5.0 mM ammonium formate in water -5.0 mM ammonium formate in methanol (30:70, v/v) over 3.0 min on reversed-stationary phase. The detection was performed using a triple-quadrupole tandem mass spectrometer in multiple-reaction monitoring mode. The developed method was validated with lower limit of quantification of 10 ng/mL. The calibration curve was linear over 10-2000 ng/mL (R{sup 2} > 0.99). The method validation parameters met the acceptance criteria. The spiked samples and standard solutions were stable under conditions for storage and handling. The reliable method was successfully applied to real sample analyses and thus a pharmacokinetic study in 27 healthy Korean male volunteers.

  14. Validated LC-MS/MS Method for the Determination of Scopoletin in Rat Plasma and Its Application to Pharmacokinetic Studies

    Directory of Open Access Journals (Sweden)

    Yingchun Zeng

    2015-10-01

    Full Text Available A rapid, sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometric method was developed and validated for the quantification of scopoletin in rat plasma. After the addition of the internal standard xanthotoxin, plasma samples were pretreated by a simple one-step protein precipitation with acetonitrile-methanol (2:1, v/v. Chromatographic separation was achieved on a Diamonsil ODS chromatography column using gradient elution with the mobile phase consisting of acetonitrile and 0.1% formic acid. The determination was performed by positive ion electrospray ionization in multiple reaction monitoring mode. The calibration curve was linear over the concentration range of 5–1000 ng/mL (r = 0.9996. The intra- and inter-day precision (RSD% was less than 6.1%, and the accuracy (RE% was from −3.0%–2.5%. This method was successfully applied to the pharmacokinetic research of scopoletin in rats after intravenous (5 mg/kg or oral (5, 10 and 20 mg/kg administration. The result showed that oral bioavailability with a dose of 5 mg/kg was 6.62% ± 1.72%, 10 mg/kg, 5.59% ± 1.16%, and 20 mg/kg, 5.65% ± 0.75%.

  15. Precolumn derivatization followed by liquid chromatographic separation and determination of tramiprosate in rat plasma by fluorescence detector: application to pharmacokinetics.

    Science.gov (United States)

    Rao, R Nageswara; Maurya, Pawan K; Shinde, Dhananjay D; Khalid, Sara

    2011-05-15

    Alzheimer disease (AD) is characterized pathologically by extracellular amyloid deposits composed of amyloid β (Aβ) protein. A simple and rapid method using HPLC with fluorescence detector was developed and validated for determination of tramiprosate in rat plasma. Pre-column derivatization of the deproteinized rat plasma was carried out using o-phthaldialdehyde (OPA) as a fluorescent reagent in presence of 3-mercaptopropionic acid. The liquid chromatographic separation was achieved on a Kromasil C18 column using methanol:acetonitrile: 20 mM phosphate buffer pH 7.5 (8.0:17.5:74.5 v/v/v) as a mobile phase in an isocratic elution mode. The eluents were monitored by a fluorescence detector set at 330 and 450 nm of excitation and emission wavelength respectively. Vigabatrin was used as an internal standard. The method was linear within the range 30.0-1000.0 ng/mL. Design of experiments (DOE) was used to evaluate the robustness of the method. The developed method was applied to study the pharmacokinetics of tramiprosate in rats. Copyright © 2011. Published by Elsevier B.V.

  16. Pharmacokinetics of repeated sodium salicylate administration to laying hens: evidence for time dependent increase in drug elimination from plasma and eggs.

    Directory of Open Access Journals (Sweden)

    Błażej Poźniak

    Full Text Available Salicylates were the first non-steroid anti-inflammatory drugs (NSAIDs to be used in any species and are still widely used in humans and livestock. However, the data on their pharmacokinetics in animals is limited, especially after repeated administration. Evidence exist that in chickens (Gallus gallus salicylate (SA may induce its own elimination. The aim of this study was to investigate salicylate pharmacokinetics and egg residues during repeated administration of sodium salicylate (SS to laying hens. Pharmacokinetics of SA was assessed during 14 d oral administration of SS at daily doses of 50 mg/kg and 200 mg/kg body weight to laying hens. On the 1st, 7th and 14th d a 24 h-long pharmacokinetic study was carried out, whereas eggs were collected daily. Salicylate concentrations in plasma and eggs were determined using high-performance liquid chromatography with ultraviolet detection and pharmacokinetic variables were calculated using a non-compartmental model. Mean residence time (MRT, minimal plasma concentration (Cmin, C16h and elimination half-life (T1/2el of SA showed gradual decrease in layers administered with a lower dose. Total body clearance (ClB increased. Layers administered with the higher dose showed a decrease only in the T1/2el. In the low dose group, SA was found only in the egg white and was low throughout the experiment. Egg whites from the higher dose group showed initially high SA levels which significantly decreased during the experiment. Yolk SA levels were lower and showed longer periods of accumulation and elimination. Repeated administration of SS induces SA elimination, although this effect may differ depending on the dose and production type of a chicken. Decreased plasma drug concentration may have clinical implications during prolonged SS treatment.

  17. Simultaneous determination of five components in rat plasma by UPLC-MS/MS and its application to a comparative pharmacokinetic study in Baihe Zhimu Tang and Zhimu extract.

    Science.gov (United States)

    Li, Guolong; Tang, Zhishu; Yang, Jie; Duan, Jinao; Qian, Dawei; Guo, Jianming; Zhu, Zhenhua; Liu, Hongbo

    2015-04-15

    Baihe Zhimu Tang (BZT) is a famous traditional Chinese medicine recipe to treat dry coughing due to yin deficiency and for moisturizing the lungs. Zhimu is an essential ingredient in BZT used to treat inflammation, fever and diabetes. The most important active components in Zhimu are flavonoids such as neomangiferin, mangiferin, and steroid saponins (e.g., timosaponin BII, anemarsaponin BIII, timosaponin AIII). The aim of this study was to compare the pharmacokinetics of mangiferin, neomangiferin, timosaponin BII, anemarsaponin BIII and timosaponin AIII in rat plasma after oral administration of BZT and Zhimu extract (ZME). A sensitive, reliable and robust LC-MS/MS method to simultaneously determine steroid saponins and flavonoids in rat plasma was successfully validated. Significant differences (p < 0.05) were found in the pharmacokinetic parameters of timosaponin BII, anemarsaponin BIII and timosaponin AIII between BZT and ZME. It was surmised that formula compatibility could significantly influence the pharmacokinetics of BZT and our study is the first to study the administration of BZT based on pharmacokinetic studies.

  18. Population pharmacokinetic study of benznidazole in pediatric Chagas disease suggests efficacy despite lower plasma concentrations than in adults.

    Directory of Open Access Journals (Sweden)

    Jaime Altcheh

    2014-05-01

    Full Text Available Chagas disease, caused by the parasite Trypanosoma cruzi, can lead to long term cardiac morbidity. Treatment of children with benznidazole is effective, but no pediatric pharmacokinetics data are available and clinical pharmacology information on the drug is scarce.Prospective population pharmacokinetic (PK cohort study in children 2-12 years old with Chagas disease treated with oral benznidazole 5-8 mg/kg/day BID for 60 days. (clinicaltrials.gov #NCT00699387.Forty children were enrolled in the study. Mean age was 7.3 years. A total of 117 samples were obtained from 38 patients for PK analysis. A one compartment model best fit the data. Weight-corrected clearance rate (CL/F showed a good correlation with age, with younger patients having a significantly higher CL/F than older children and adults. Simulated median steady-state benznidazole concentrations, based on model parameters, were lower for children in our study than for adults and lowest for children under 7 years of age. Treatment was efficacious in the 37 patients who completed the treatment course, and well tolerated, with few, and mild, adverse drug reactions (ADRs.Observed benznidazole plasma concentrations in children were markedly lower than those previously reported in adults (treated with comparable mg/kg doses, possibly due to a higher CL/F in smaller children. These lower blood concentrations were nevertheless associated to a high therapeutic response in our cohort. Unlike adults, children have few adverse reactions to the drug, suggesting that there may be a direct correlation between drug concentrations and incidence of ADRs. Our results suggest that studies with lower doses in adults may be warranted.ClinicalTrials.gov NCT00699387.

  19. The plasma and cerebrospinal fluid pharmacokinetics of erlotinib and its active metabolite (OSI-420) after intravenous administration of erlotinib in non-human primates.

    Science.gov (United States)

    Meany, Holly J; Fox, Elizabeth; McCully, Cynthia; Tucker, Chris; Balis, Frank M

    2008-08-01

    Erlotinib hydrochloride is a small molecule inhibitor of epidermal growth factor receptor (EGFR). EGFR is over-expressed in primary brain tumors and solid tumors that metastasize to the central nervous system. We evaluated the plasma and cerebrospinal fluid (CSF) pharmacokinetics of erlotinib and its active metabolite OSI-420 after an intravenous (IV) dose in a non-human primate model. Erlotinib was administered as a 1 h IV infusion to four adult rhesus monkeys. Serial blood and CSF samples were drawn over 48 h and erlotinib and OSI-420 were quantified with an HPLC/tandem mass spectroscopic assay. Pharmacokinetic parameters were estimated using non-compartmental and compartmental methods. CSF penetration was calculated from the AUC(CSF):AUC(plasma). Erlotinib disappearance from plasma after a short IV infusion was biexponential with a mean terminal half-life of 5.2 h and a mean clearance of 128 ml/min per m(2). OSI-420 exposure (AUC) in plasma was 30% (range 12-59%) of erlotinib, and OSI-420 clearance was more than 5-fold higher than erlotinib. Erlotinib and OSI-420 were detectable in CSF. The CSF penetration (AUC(CSF):AUC(plasma)) of erlotinib and OSI-420 was OSI-420 are measurable in CSF after an IV dose. The drug exposure (AUC) in the CSF is limited relative to total plasma concentrations but is substantial relative the free drug exposure in plasma.

  20. Pharmacokinetic study of arctigenin in rat plasma and organ tissue by RP-HPLC method.

    Science.gov (United States)

    He, Fan; Dou, De-Qiang; Hou, Qiang; Sun, Yu; Kang, Ting-Guo

    2013-01-01

    A high-performance liquid chromatography (HPLC) technique was developed for the determination of arctigenin in plasma and various organs of rats after the oral administration of 30, 50 and 70 mgkg(-1) of arctigenin to the Sprague-Dawley rats. Results showed that the validated HPLC method was simple, fast, reproducible and suitable to the determination of arctigenin in rat plasma and organ tissue and one-compartmental model with zero-order absorption process can well describe the changes of arctigenin concentration in the plasma. The concentration of compound was highest in the spleen, less in the liver and the least in the lung.

  1. LC determination and pharmacokinetic study of the main phenolic components of Portulaca oleracea L. extract in rat plasma after oral administration.

    Science.gov (United States)

    Cheng, Zhongzhe; Wang, Dong; Zhang, Wenjie; Du, Yang; Wang, Yunjiao; Zhai, Yanjun; Ying, Xixiang; Kang, Tingguo

    2012-01-01

    This study investigated the pharmacokinetics of hesperidin (HP), ferulic acid (FA) and p-coumaric acid (CA) in rat plasma after oral administration of Portulaca oleracea L. extract (POE). The plasma concentrations were determined by HPLC with vitexin-2″-O-rhamnoside (VR) as internal standard. The calibration curves were linear over the range 0.1-5 µg mL(-1), 0.1-5 µg mL(-1)and 0.015-3 µg mL(-1) for HP, FA and CA, respectively. The validated method was suitable to the pharmacokinetic study of HP, FA and CA in rats after oral administration at a single dose of POE.

  2. Development and Validation of a HPLC Method to Determine Griseofulvin in Rat Plasma: Application to Pharmacokinetic Studies

    Directory of Open Access Journals (Sweden)

    Bo Wei

    2008-01-01

    Full Text Available A simple, specific, sensitive, and rapid high performance liquid chromatography (HPLC method for the determination of griseofulvin in small volumes of rat plasma was developed and validated using warfarin as an internal standard. Biological sample preparation involved simple extraction with acetonitrile, followed by dilution with aqueous mobile phase buffer (20 mM sodium dihydrogen phosphate, pH 3.5 to eliminate any chromatographic solvent effects. Griseofulvin and warfarin were baseline separated and quantitated on a C 18 reversed phase column (4.6 x 150 mm, 3.5 µm, using a mobile phase composed of a 20 mM aqueous solution of sodium dihydrogen phosphate-acetonitrile (55:45, v/v, pH 3.5 delivered at a flow rate of 1.0 mL/min, and with fluorescence detection (λ excitation = 300 nm, λ emission = 418 nm. The method was proven to be linear over a plasma griseofulvin concentration range of 10 to 2500 ng/mL with a mean correlation coefficient of 0.9996. The intra-day and inter-day accuracy (relative error were in the range of 0.89% to 9.26% and 0.71% to 7.68%, respectively. The within-day precision (coefficient of variation was less than 3.0% and the between-day precision was less than 7.5%. The mean recovery of griseofulvin from rat plasma was found to be 99.2%. The limit of detection (LOD and the limit of quantification (LOQ of griseofulvin were determined to be 1 ng/mL and 10 ng/mL, respectively. The developed method was successfully applied to quantitatively assess the pharmacokinetics of griseofulvin in rats following a single 50 mg/kg oral dose of the drug.

  3. Studies on separation and pharmacokinetics of m-nisoldipine enantiomers in beagle dog plasma by LC/MS/MS.

    Science.gov (United States)

    Li, Min; Yuan, Lin; Li, Xiuqing; Zhi, Xuran; Sheng, Ning; Zhang, Lantong

    2013-11-01

    A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric (LC/MS/MS) method was developed and validated for the separation and determination of m-nisoldipine enantiomers in beagle dog plasma. Samples were pretreated by a single-step protein precipitation with acetonitrile. After m-nisoldipine racemic administration to beagle dogs, samples of m-nisoldipine enantiomers in beagle dog plasma were separated and determined on a ULTRON ES-OVM column (150 × 4.6 mm, 5 μm) at 20°C with a mobile phase consisted of methanol-acetonitrile-ammonium acetate (pH 7.0; 2mM) (15:15:70, v/v/v) at a flow rate of 0.8 mL/min. Chromatograms were monitored at 237 nm, and the API 4000 triple quadrupole mass spectrometer was operated in multiple reaction monitoring (MRM) scan mode using ElectroSpray ionization (ESI) source. The good linearity (rs=0.9958 and rr=0.9983) were found in the range 0.25-20 ng/mL. The lower limit of quantification (LLOQ) obtained was 0.25 ng/mL (n=6). All the validation data, such as accuracy, precision, intra-day and inter-day repeatability, were within the required limits. The method was successfully applied to separation and pharmacokinetics of m-nisoldipine enantiomers in beagle dog plasma. The result of statistics analysis shows that there are no significant differences between R-(-)-m-nisoldipine and S-(+)-m-nisoldipine (p>0.05). The study provides necessary evidences for the research and new drug development of m-nisoldipine enantiomers. Copyright © 2013. Published by Elsevier B.V.

  4. UPLC–MS/MS for the determination of azilsartan in beagle dog plasma and its application in a pharmacokinetics study

    Directory of Open Access Journals (Sweden)

    Cheng Gong

    2015-06-01

    Full Text Available The purpose of the study is to develop an ultra performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS to determinate the concentration of azilsartan in the dog plasma. After precipitated by methanol, the plasma sample containing azilsartan and diazepam (internal standard, IS was determined by UPLC–MS/MS. The mobile phase consisted of acetonitrile-water was pumped at a flow rate of 0.3 ml/min in gradient elution. Kinetex 2.6 μ XB-C18 column (50 × 2.1 mm, 100 Å; Phenomenex, USA were used for LC separations. The column temperature was 30 °C and the injection volume was 5 μl. The electrospray ionization (ESI and multiple reaction monitoring (MRM were applied at the transitions of m/z 457 → 279 (azilsartan and m/z 285 → 193 (diazepam, respectively. The developed method was identified a good linearity over a concentration range of 2.5–5000 ng/ml. The lower limit of quantitation (LLOQ was 2.5 ng/ml. The intra-day and inter-day precision (relative standard deviation, RSD% were less than 10% and accuracy (relative error, RE % was less than 5% at three quality control levels. The extraction recovery of azilsartan at three quality control levels were 82.41 ± 0.68%, 98.66 ± 11.00%, 102.43 ± 0.82%. And the recovery for IS (100 ng/ml was 91.75 ± 0.54%. A validated UPLC–MS/MS method was firstly developed for the quantification of azilsartan in dog plasma and it was applied to the pharmacokinetics study.

  5. Clinical Determinants of Target Non-Attainment of Linezolid in Plasma and Interstitial Space Fluid: A Pooled Population Pharmacokinetic Analysis with Focus on Critically Ill Patients.

    Science.gov (United States)

    Minichmayr, Iris K; Schaeftlein, André; Kuti, Joseph L; Zeitlinger, Markus; Kloft, Charlotte

    2017-06-01

    We aimed to assess linezolid pharmacokinetics in the plasma and interstitial space fluid (ISF) of patients with sepsis, diabetic foot infections or cystic fibrosis and healthy volunteers. The impacts of joint characteristics and disease on plasma and target-site exposure were to be identified together with the benefit of dose intensification in critically ill patients. Rich plasma (n = 1598) and ISF concentrations in subcutaneous adipose (n = 1430) and muscle tissue (n = 1089) measured by microdialysis were pooled from three clinical trials with 51 individuals receiving 600 mg of intravenous and oral linezolid. All data were analysed simultaneously by a population approach also considering methodological aspects of microdialysis. The impact of covariates on the attainment of the pharmacokinetic/pharmacodynamic targets, AUC/MIC = 100 (area under the concentration-time curve/minimum inhibitory concentration) and fT >MIC  = 99 % (time that unbound concentrations exceed the MIC), was assessed by deterministic and Monte Carlo simulations. A two-compartment pharmacokinetic model with nonlinear elimination and tissue distribution factors accounting for differences between plasma and ISF concentrations adequately predicted all measurements. Clearance (CL) was highest in septic patients (11.2 L/h vs. CL Healthy /CL Cystic fibrosis /CL Diabetic  = 7.67/6.87/6.35 L/h). Penetration into subcutaneous adipose ISF was lowest in diabetic patients (-34.9 % compared with healthy volunteers). Creatinine clearance and total body weight further impacted linezolid exposure. To achieve timely efficacious therapy, front-loaded dosing and continuous infusion seemed beneficial in septic patients. Our analysis suggests that after standard linezolid doses, particularly patients with sepsis and conserved renal function are at risk of not attaining pharmacokinetic/pharmacodynamic targets and would benefit from initial dose intensification.

  6. Sensitive determination of 4-O-methylhonokiol in rabbit plasma by high performance liquid chromatography and application to its pharmacokinetic investigation

    Directory of Open Access Journals (Sweden)

    Ming-Yue Li

    2011-05-01

    Full Text Available A novel high Performance liquid Chromatographie method was developed for the determination of 4-O-methylhonokiol in rabbit plasma and was applied to its pharmacokinetic investigation. Plasma samples were treated by one-fold volume of methanol and acetonitrile to remove the interference proteins. A reverse phase column of SHIM-PACK VP-ODS (150 mm × 4.6 mm, 5.0 Mm was used to separate 4-O-methylhonokiol in the plasma samples. The detection limit of 4-O-methylhonokiol was 0.2 μg/L and the linear ränge was 0.012 – 1.536 μg/L. The good extraction recoveries were obtained for the spiked samples (84.7%, 89.3% and 87.7% for low, middle and high concentrations of added Standards, respectively. The relative standard deviation of intra-day and inter-day precisions was in the ränge from 0.6% to 13.5%. The pharmacokinetic study of 4-O-methylhonokiol was made and the results from the plasma-concentration curve of 4-O-methylhonokiol showed a two-apartment open model. This work developed a sensitive, stable and rapid HPLC method for the determination of 4-O-methylhonokiol and the developed method has been successfully applied to a pharmacokinetic study of 4-O-methylhonokiol. Keywords: 4-O-methylhonokiol, Cortex Magnoliae Officinalis, high Performance liquid chromatography, pharmacokinetic

  7. Application of a pharmacokinetics-pharmacodynamics approach to the free propofol plasma levels during coronary artery bypass grafting surgery with hypothermic cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    Carlos R. Silva-Filho

    2018-02-01

    Full Text Available OBJECTIVES: The objective of this study was to apply a pharmacokinetics-pharmacodynamics approach to investigate the free propofol plasma levels in patients undergoing coronary artery bypass grafting under hypothermic conditions compared with the off-pump procedure. METHODS: Nineteen patients scheduled for on-pump coronary artery bypass grafting under hypothermic conditions (n=10 or the equivalent off-pump surgery (n=9 were anesthetized with sufentanil and propofol target-controlled infusion (2 μg/mL during surgery. The propofol concentration was then reduced to 1 μg/mL, and a pharmacokinetics-pharmacodynamics analysis using the maximum-effect-sigmoid model obtained by plotting the bispectral index values against the free propofol plasma levels was performed. RESULTS: Significant increases (two- to five-fold in the free propofol plasma levels were observed in the patients subjected to coronary artery bypass grafting under hypothermic conditions. The pharmacokinetics of propofol varied according to the free drug levels in the hypothermic on-pump group versus the off-pump group. After hypothermic coronary artery bypass was initiated, the distribution volume increased, and the distribution half-life was prolonged. Propofol target-controlled infusion was discontinued when orotracheal extubation was indicated, and the time to patient extubation was significantly higher in the hypothermic on-pump group than in the off-pump group (459 versus 273 min, p=0.0048. CONCLUSIONS: The orotracheal intubation time was significantly longer in the hypothermic on-pump group than in the off-pump group. Additionally, residual hypnosis was identified through the pharmacokinetics-pharmacodynamics approach based on decreases in drug plasma protein binding in the hypothermic on-pump group, which could explain the increased hypnosis observed with this drug in this group of patients.

  8. Determination of the neuropharmacological drug nodakenin in rat plasma and brain tissues by liquid chromatography tandem mass spectrometry: Application to pharmacokinetic studies.

    Science.gov (United States)

    Song, Yingshi; Yan, Huiyu; Xu, Jingbo; Ma, Hongxi

    2017-09-01

    A rapid and sensitive liquid chromatography tandem mass spectrometry detection using selected reaction monitoring in positive ionization mode was developed and validated for the quantification of nodakenin in rat plasma and brain. Pareruptorin A was used as internal standard. A single step liquid-liquid extraction was used for plasma and brain sample preparation. The method was validated with respect to selectivity, precision, accuracy, linearity, limit of quantification, recovery, matrix effect and stability. Lower limit of quantification of nodakenin was 2.0 ng/mL in plasma and brain tissue homogenates. Linear calibration curves were obtained over concentration ranges of 2.0-1000 ng/mL in plasma and brain tissue homogenates for nodakenin. Intra-day and inter-day precisions (relative standard deviation, RSD) were <15% in both biological media. This assay was successfully applied to plasma and brain pharmacokinetic studies of nodakenin in rats after intravenous administration. Copyright © 2017 John Wiley & Sons, Ltd.

  9. Comparison of Omadacycline and Tigecycline Pharmacokinetics in the Plasma, Epithelial Lining Fluid, and Alveolar Cells of Healthy Adult Subjects.

    Science.gov (United States)

    Gotfried, Mark H; Horn, Karolyn; Garrity-Ryan, Lynne; Villano, Stephen; Tzanis, Evan; Chitra, Surya; Manley, Amy; Tanaka, S Ken; Rodvold, Keith A

    2017-09-01

    The steady-state concentrations of omadacycline and tigecycline in the plasma, epithelial lining fluid (ELF), and alveolar cells (AC) of 58 healthy adult subjects were obtained. Subjects were administered either omadacycline at 100 mg intravenously (i.v.) every 12 h for two doses followed by 100 mg i.v. every 24 h for three doses or tigecycline at an initial dose of 100 mg i.v. followed by 50 mg i.v. every 12 h for six doses. A bronchoscopy and bronchoalveolar lavage were performed once in each subject following the start of the fifth dose of omadacycline at 0.5, 1, 2, 4, 8, 12, or 24 h and after the start of the seventh dose of tigecycline at 2, 4, 6, or 12 h. The value of the area under the concentration-time curve (AUC) from time zero to 24 h postdosing (AUC 0-24 ) (based on mean concentrations) in ELF and the ratio of the ELF to total plasma omadacycline concentration based on AUC 0-24 values were 17.23 mg · h/liter and 1.47, respectively. The AUC 0-24 value in AC was 302.46 mg · h/liter, and the ratio of the AC to total plasma omadacycline concentration was 25.8. In comparison, the values of the AUC from time zero to 12 h postdosing (AUC 0-12 ) based on the mean concentrations of tigecycline in ELF and AC were 3.16 and 38.50 mg · h/liter, respectively. The ratio of the ELF and AC to total plasma concentrations of tigecycline based on AUC 0-12 values were 1.71 and 20.8, respectively. The pharmacokinetic advantages of higher and sustained concentrations of omadacycline compared to those of tigecycline in plasma, ELF, and AC suggest that omadacycline is a promising antibacterial agent for the treatment of lower respiratory tract bacterial infections caused by susceptible pathogens. Copyright © 2017 Gotfried et al.

  10. Comparative pharmacokinetics and bioavailability of albendazole sulfoxide in sheep and goats, and dose-dependent plasma disposition in goats.

    Science.gov (United States)

    Aksit, Dilek; Yalinkilinc, Hande Sultan; Sekkin, Selim; Boyacioğlu, Murat; Cirak, Veli Yilgor; Ayaz, Erol; Gokbulut, Cengiz

    2015-05-27

    The aims of this study were to compare the pharmacokinetics of albendazole sulfoxide (ABZ-SO, ricobendazole) in goats and sheep at a dose of 5 g/kg bodyweight (BW), after intravenous (IV) and subcutaneous (SC) administrations, and to investigate the effects of increased doses (10 and 15 mg/kg BW) on the plasma disposition of ABZ-SO in goats following SC administration. A total of 16 goats (Capra aegagrus hircus, eight males and eight females) and 8 sheep (Ovis aries, four males and four females) 12-16 months old and weighing 20-32 kg, were used. The study was designed according to two-phase crossover study protocol. In Phase-1, eight sheep were assigned as Group I and 16 goats were allocated into two groups (Group II and Group III). ABZ-SO was applied to Group I (sheep) and Group II (goats) animals subcutaneously, and to Group III (goats) animals intravenously, all at a dose rate of 5 mg/kg BW. In Phase-2, the sheep in the Group I received ABZ-SO intravenously in a dose of 5 mg/kg BW; the goats in Group II and Group III received ABZ-SO subcutaneously at a dose of 10 mg/kg and 15 mg/kg BW, respectively. Blood samples were collected from the jugular vein at different times between 1 and 120 h after drug administrations. The plasma concentrations of ABZ-SO and its metabolites were analysed by high performance liquid chromatography. In goats, the area under the curve, terminal half-life and plasma persistence of ABZ-SO were significantly smaller and shorter, respectively, compared with those observed in sheep following both IV and SC administrations at a dose of 5 mg/kg BW. On the other side, dose-dependent plasma dispositions of ABZ-SO were observed following SC administration at increased doses (10 and 15 mg/kg) in goats. Consequently, ABZ-SO might be used at higher doses to provide higher plasma concentration and thus to achieve greater efficacy against the target parasites.

  11. Preclinical pharmacokinetics, biodistribution, radiation dosimetry and acute toxicity studies required for regulatory approval of a Clinical Trial Application for a Phase I/II clinical trial of 111In-BzDTPA-pertuzumab

    International Nuclear Information System (INIS)

    Lam, Karen; Chan, Conrad; Done, Susan J.; Levine, Mark N.; Reilly, Raymond M.

    2015-01-01

    Introduction: 111 In-BzDTPA-pertuzumab is a novel imaging probe for detecting changes in HER2 expression in breast cancer (BC) caused by treatment with trastuzumab (Herceptin). Our aim was to evaluate the pharmacokinetics, normal tissue biodistribution, radiation dosimetry and acute toxicity of 111 In-BzDTPA-pertuzumab in non-tumor bearing mice in order to obtain regulatory approval to advance this agent to a first-in-humans Phase I/II clinical trial. Methods: Biodistribution and pharmacokinetic studies were performed in non-tumor bearing Balb/c mice injected i.v. with 111 In-BzDTPA-pertuzumab (2.5 MBq; 2 μg). The cumulative number of disintegrations per source organ derived from the biodistribution data was used to predict the radiation absorbed doses in humans using OLINDA/EXM software. Acute toxicity was studied at two weeks post-injection of 111 In-BzDTPA-pertuzumab (1.0 MBq, 20 μg) with comparison to control mice injected with unlabeled BzDTPA-pertuzumab (20 μg) or Sodium Chloride Injection USP. The dose of 111 In-BzDTPA-pertuzumab corresponded to 23-times the human radioactivity dose and 10-times the protein dose on a MBq/kg and mg/kg basis, respectively. Toxicity was assessed by monitoring body mass, complete blood cell count (CBC), hematocrit (Hct), hemoglobin (Hb), serum creatinine (SCr) and alanine aminotransferease (ALT) and by histopathological examination of tissues at necropsy. Results: 111 In-BzDTPA-pertuzumab exhibited a biphasic elimination from the blood with a distribution half-life (t 1/2 α) of 3.8 h and an elimination half-life (t 1/2 β) of 228.2 h. The radiopharmaceutical was distributed mainly in the blood, heart, lungs, liver, kidneys and spleen. The projected whole-body radiation absorbed dose in humans was 0.05 mSv/MBq corresponding to a total of 16.8 mSv for three separate administrations of 111 In-BzDTPA-pertuzumab (111 MBq) planned for the Phase I/II trial. There were slight changes in Hb and SCr levels associated with

  12. Determination of cyclovirobuxine D in human plasma by liquid chromatography tandem mass spectrometry and application in a pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Ling-li Mu

    2011-10-01

    Full Text Available A sensitive and reliable method based on liquid chromatography tandem mass spectrometry (LC–MS/MS for the quantitation of cyclovirobuxine D in human plasma has been developed and validated. Sample preparation by solid phase extraction was followed by separation on a CN column with a mobile phase of methanol–water (95:5, v/v containing 0.2% formic acid. Mass spectrometric detection in the positive ion mode was carried out by selected reaction monitoring (SRM of the transitions at m/z 403.0→372.0 for cyclovirobuxine D and m/z 325.0→234.0 for citalopram (internal standard. The method was linear in the range 10–200 ng/L with LLOQ of 10 ng/L, recovery >85%, and no significant matrix effects. Intra- and inter-day precisions were all <9% with accuracies of 94.0–104.8%. The method was successfully applied to a pharmacokinetic study involving a single oral administration of a 2 mg cyclovirobuxine D tablet to twenty-two healthy Chinese volunteers.

  13. Preclinical pharmacokinetics, tissue distribution and plasma protein binding of sodium (±-5-bromo-2-(α-hydroxypentyl benzoate (BZP, an innovative potent anti-ischemic stroke agent

    Directory of Open Access Journals (Sweden)

    Xin Tian

    2016-08-01

    Full Text Available Sodium (±-5-bromo-2-(α-hydroxypentyl benzoate (BZP is a potential cardiovascular drug and exerts potent neuroprotective effect against transient and long-term ischemic stroke in rats. BZP could convert into 3-butyl-6-bromo-1(3H-isobenzofuranone (Br-NBP in vitro and in vivo. However, the pharmacokinetic profiles of BZP and Br-NBP still have not been evaluated. For the purpose of investigating the pharmacokinetic profiles, tissue distribution and plasma protein binding of BZP and Br-NBP, a rapid, sensitive and specific method based on liquid chromatography coupled to mass spectrometry (LC-MS/MS has been developed for determination of BZP and Br-NBP in biological samples. The results indicated that BZP and Br-NBP showed a short elimination half-life, and pharmacokinetic profile in rats (3, 6 and 12 mg/kg; i.v. and beagle dogs (1, 2 and 4 mg/kg; i.v.gtt were obtained after single dosing of BZP. After multiple dosing of BZP, there was no significant accumulation of BZP and Br-NBP in the plasma of rats and beagle dogs. Following i.v. single dose (6 mg/kg to rats, BZP and Br-NBP were distributed rapidly into all tissues examined, with the highest concentrations of BZP and Br-NBP in lung and kidney, respectively. The brain distribution of Br-NBP in middle cerebral artery occlusion (MCAO rats was more than in normal rats (P<0.05. The plasma protein binding degree of BZP at three concentrations (8000, 20000 and 80000 ng/mL from rat, beagle dog and human plasma were 98.1~98.7%, 88.9~92.7% and 74.8%~83.7% respectively. In conclusion, both BZP and Br-NBP showed short half-life, good dose-linear pharmacokinetic profile, wide tissue distribution and different degree protein binding to various species plasma. This was the first preclinical pharmacokinetic investigation of BZP and Br-NBP in both rats and beagle dogs, which provided vital guidance for further preclinical research and the subsequent clinical trials.

  14. Doxorubicin-loaded QuadraSphere microspheres: plasma pharmacokinetics and intratumoral drug concentration in an animal model of liver cancer.

    Science.gov (United States)

    Lee, Kwang-Hun; Liapi, Eleni A; Cornell, Curt; Reb, Philippe; Buijs, Manon; Vossen, Josephina A; Ventura, Veronica Prieto; Geschwind, Jean-Francois H

    2010-06-01

    The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.

  15. Doxorubicin-Loaded QuadraSphere Microspheres: Plasma Pharmacokinetics and Intratumoral Drug Concentration in an Animal Model of Liver Cancer

    International Nuclear Information System (INIS)

    Lee, Kwang-Hun; Liapi, Eleni A.; Cornell, Curt; Reb, Philippe; Buijs, Manon; Vossen, Josephina A.; Ventura, Veronica Prieto; Geschwind, Jean-Francois H.

    2010-01-01

    The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.

  16. Determination of esculentoside A in dog plasma by LC-MS/MS method: application to pre-clinical pharmacokinetics.

    Science.gov (United States)

    Guan, Xiaoduo; Chang, Huichao; Sun, Fanlu; Chen, Xiaohui; Zhang, Wen; Fan, Guorong

    2013-01-01

    A simple and rapid high performance liquid chromatography electrospray ionization ion-trap tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantitative determination of esculentoside A (EsA) in dog plasma using ginsenoside Rg1 as the internal standard (IS). After liquid-liquid extraction (LLE) with n-butanol, the analyte and IS were separated on a Diamonsil C(18) (2.1 mm × 50 mm, 3 μm) column with the mobile phase of methanol-water containing 0.1% acetic acid (70:30, v/v) at a flow rate of 0.2 ml/min. An ion trap mass spectrometer equipped with an electrospray ionization source performed in selected reaction monitoring (SRM) mode was used as the detector. The precursor-product ion transitions were m/z 849.3 [M+Na](+)→m/z 805.3 for EsA and m/z 823.3 [M+Na](+)→m/z 643.3 for IS. The total chromatographic run time was 5 min. The method was sensitive enough with a lower limit of quantitation (LLOQ) of 5 ng/ml and had a good linearity (r(2)>0.997) over the linear range of 5-500 ng/ml. The mean extraction recovery of EsA from spiked plasma samples was over 75%. The intra- and inter-precisions were no more than 8.8% and accuracies were within the range of -4.6 to 8.7%. All the validated data were within the accepted criteria as stated in the FDA bioanalytical method validation guideline. The developed method was suitable for the quantification of EsA and successfully applied to the pharmacokinetic study of EsA after an oral administration to beagle dogs. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Resistance probe for energetic particle dosimetry with applications for plasma edge studies

    International Nuclear Information System (INIS)

    Wampler, W.R.

    1982-01-01

    Changes in the electrical resistance of thin carbon films caused by implantation with hydrogen, deuterium, and carbon ions were measured for various incident energies and for particle fluences in the range from 10 12 to 10 17 at./cm 2 . At low fluences the resistivity change is found to be proportional to the displacement damage caused by the incident particles. A model is presented which can be used to calculate the resistance change which is in good agreement with the measurements. It is proposed that by measuring the resistance change for carbon films exposed to the edge of magnetically confined plasmas the energy and the flux of incident ions and neutral atoms may be determined

  18. Clinical pharmacokinetics of melatonin

    DEFF Research Database (Denmark)

    Harpsøe, Nathja Groth; Andersen, Lars Peter Holst; Gögenur, Ismail

    2015-01-01

    was performed in PubMed and Embase databases. The pharmacokinetic variables included maximal plasma/serum concentration (Cmax), time to maximal plasma/serum concentration (Tmax), elimination half-life (T1/2), area-under-the-curve plasma/serum concentrations (AUC), clearance (Cl), volume of distribution (VD......) and 1602 L (4 mg, oral). Bioavailability of oral melatonin ranged from 9 to 33%. Pharmacokinetics was affected by age, caffeine, smoking, oral contraceptives, feeding status, and fluvoxamine. Critically ill patients displayed accelerated absorption and compromised elimination. CONCLUSIONS: Despite...

  19. Hard X-ray dosimetry of a plasma focus suitable for industrial radiography

    Science.gov (United States)

    Knoblauch, P.; Raspa, V.; Di Lorenzo, F.; Clausse, A.; Moreno, C.

    2018-04-01

    Dosimetric measurements of the hard X-ray emission by a small-chamber 4.7 kJ Mather-type plasma focus device capable of producing neat radiographs of metallic objects, were carried out with a set of thermoluminescent detectors TLD 700 (LiF:Mg,Ti). Measurements of the hard X-ray dose dependence with the angular position relative to the electrodes axis, are presented. The source-detector distance was changed in the range from 50 to 100 cm, and the angular positions were explored between ± 70°, relative to the symmetry axis of the electrodes. On-axis measurements show that the X-ray intensity is uniform within a half aperture angle of 6°, in which the source delivers an average dose of (1.5 ± 0.1) mGy/sr per shot. Monte Carlo calculations suggest that the energy of the electron beam responsible for the X-ray emission ranges 100-600 keV.

  20. PEEK tube-based online solid-phase microextraction-high-performance liquid chromatography for the determination of yohimbine in rat plasma and its application in pharmacokinetics study.

    Science.gov (United States)

    Xiang, Xiaowei; Shang, Bing; Wang, Xiaozheng; Chen, Qinhua

    2017-04-01

    Yohimbine is a novel compound for the treatment of erectile dysfunction derived from natural products, and pharmacokinetic study is important for its further development as a new medicine. In this work, we developed a novel PEEK tube-based solid-phase microextraction (SPME)-HPLC method for analysis of yohimbine in plasma and further for pharmacokinetic study. Poly (AA-EGDMA) was synthesized inside a PEEK tube as the sorbent for microextraction of yohimbine, and parameters that could influence extraction efficiency were systematically investigated. Under optimum conditions, the PEEK tube-based SPME method exhibits excellent enrichment efficiency towards yohimbine. By using berberine as internal standard, an online SPME-HPLC method was developed for analysis of yohimbine in human plasma sample. The method has wide linear range (2-1000 ng/mL) with an R 2 of 0.9962; the limit of detection was determined and was as low as 0.1 ng/mL using UV detection. Finally, a pharmacokinetic study of yohimbine was carried out by the online SPME-HPLC method and the results have been compared with those of reported methods. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Plasma pharmacokinetics of catechin metabolite 4'-O-Me-EGC in healthy humans.

    Science.gov (United States)

    Renouf, Mathieu; Redeuil, Karine; Longet, Karin; Marmet, Cynthia; Dionisi, Fabiola; Kussmann, Martin; Williamson, Gary; Nagy, Kornél

    2011-10-01

    Tea is an infusion of the leaves of the Camellia sinensis plant and is the most widely consumed beverage in the world after water. Green tea contains significant amounts of polyphenol catechins and represents a promising dietary component to maintain health and well-being. Epidemiological studies indicate that polyphenol intake may have potential health benefits, such as, reducing the incidence of coronary heart disease, diabetes and cancer. While bioavailability of green tea bioactives is fairly well understood, some gaps still remain to be filled, especially the identification and quantification of conjugated metabolites in plasma, such as, sulphated, glucuronidated or methylated compounds. In the present study, we aimed to quantify the appearance of green tea catechins in plasma with particular emphasis on their methylated forms. After feeding 400 mL of green tea, 1.25% infusion to 9 healthy subjects, we found significant amounts of EC, EGC and EGCg in plasma as expected. EGC was the most bioavailable catechin, and its methylated form (4'-O-Me-EGC) was also present in quantifiable amounts. Its kinetics followed that of its parent compound. However, the relative amount of the methylated form of EGC was lower than that of the parent compound, an important aspect which, in the literature, has been controversial so far. The quantitative results presented in our study were confirmed by co-chromatography and accurate mass analysis of the respective standards. We show that the relative abundance of 4'-O-Me-EGC is ~40% compared to the parent EGC. 4'-O-Me-EGC is an important metabolite derived from catechin metabolism. Its presence in significant amounts should not be overlooked when assessing human bioavailability of green tea.

  2. Simultaneous determination of borneol and its metabolite in rat plasma by GC–MS and its application to pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Xiu-Man Sun

    2014-10-01

    Full Text Available A gas chromatography mass spectrometry (GC–MS method has been developed and fully validated for the simultaneous determination of natural borneol (NB and its metabolite, camphor, in rat plasma. Following a single liquid–liquid extraction, the analytes were separated using an HP-5MS capillary column (0.25 mm×30 m×0.25 μm and analyzed by MS in the selected ion monitoring mode. Selected ion monitor (m/z of borneol, camphor and internal standard was 95, 95 and 128, respectively. Linearity, accuracy, precision and extraction recovery of the analytes were all satisfactory. The method was successfully applied to pharmacokinetic studies of NB after oral administration to Wistar rats. Keywords: Borneol, Camphor, Simultaneous determination, Pharmacokinetics, GC–MS

  3. An HPLC Method for Microanalysis and Pharmacokinetics of Marine Sulfated Polysaccharide PSS-Loaded Poly Lactic-co-Glycolic Acid (PLGA Nanoparticles in Rat Plasma

    Directory of Open Access Journals (Sweden)

    Hua-Shi Guan

    2013-04-01

    Full Text Available This study was aimed at developing a sensitive and selective HPLC method with postcolumn fluorescence derivatization for the detection of propylene glycol alginate sodium sulfate (PSS in rat plasma. Plasma samples were prepared by a simple and fast ultrafiltration method. PSS was extracted from rat plasma with d-glucuronic acid as internal standard. Isocratic chromatographic separation was performed on a TSKgel G2500 PWxL column with the mobile phase of 0.1 M sodium sulfate at a flow rate of 0.5 mL/min. Analyte detection was achieved by fluorescence detection (FLD at 250 nm (excitation and 435 nm (emission using guanidine hydrochloride as postcolumn derivatizing reagent in an alkaline medium at 120 °C. The calibration curve was linear over a concentration range of 1–500 μg/mL, and the lower limit of detection (LLOD was found to be 250 ng/mL. This validated method was applied successfully to the pharmacokinetic study of PSS and PSS-loaded poly lactic-co-glycolic acid (PLGA nanoparticles (PSS-NP in rat plasma after a single intravenous (PSS only and oral administration (PSS and PSS-NP. Significant differences in the main pharmacokinetic parameters of PSS and PSS-NP were observed. The relative bioavailability of PSS-NP was 190.10% compared with PSS which shows that PSS-NP can improve oral bioavailability.

  4. High-performance liquid chromatographic method for the determination of nicardipine in pure, pharmaceutical preparations and plasma and its application to pharmacokinetics in humans

    Directory of Open Access Journals (Sweden)

    Sheikha Mohammed Al-Ghannam

    2008-12-01

    Full Text Available A simple, sensitive and reproducible reversed-phase liquid chromatographic method has been developed and validated for the determination of nicardipine hydrochloride (NC in pure, pharmaceutical preparations, human plasma and the study of the pharmacokinetics of the drug in human body. Nicardipine in plasma were extracted with hexane-butanol (12:1,v/v after addition of borate buffer (0.5 M, pH=9.0, and then measured by HPLC-UV using a Waters Symmetry C18 column as stationary phase and methanol– triethylamine buffer (0.01M pH 4 with acetic acid (70:30 as mobile phase. Nicardipine was quantified by ultraviolet absorbance at 353 nm. The method proved to be linear in the pure drug in the ranges of 15-200 ng/mL (r=0.9989 and 5-40 µg/mL (r=0.9995, and for the pharmaceutical preparations and plasma for drug concentrations in the range of 5-40 µg/mL (r =0.9992 and 25-150 ng/mL (r=0.9991, respectively. The lower limit of detection and the lower quantitation limit of NC in plasma were 11.74 and 35.57 ng/mL, respectively. The method is sensitive and reliable for pharmacokinetic studies of nicardipine in humans after the oral administration of immediate-release capsules to healthy subjects.

  5. Determination of atractylon in rat plasma by a GC–MS method and its application to a pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Han Yan

    2015-10-01

    Full Text Available A sensitive and selective method based on gas chromatography hyphenated to mass spectrometry (GC–MS was developed and validated for the determination of atractylon in rat plasma. Plasma samples were processed by liquid–liquid extraction with ethyl acetate-n-hexane (1:1, v/v using acetophenone as an internal standard (IS. Analytes were determined in selective ion monitoring (SIM mode using target ions at m/z 108.1 for atractylon and m/z 105.1 for acetophenone. The calibration curve was linear over the concentration range of 10–1000 ng/mL with lower limit of quantification of 10 ng/mL. The intra- and inter-day precision variations were not more than 10.4% and 9.6%, respectively, whilst accuracy values ranged from −6.5% to 4.9%. Extraction recovery of the assay was satisfactory. This method was successfully applied to quantification and pharmacokinetic study of atractylon in rat plasma after intragastric administration of Atractylodis extract. Keywords: Atractylon, Atractylodis, Rat plasma, Pharmacokinetics, GC–MS

  6. Pharmacokinetics of anthraquinones in rat plasma after oral administration of a rhubarb extract.

    Science.gov (United States)

    Wu, Wenjin; Yan, Ru; Yao, Meicun; Zhan, Ying; Wang, Yitao

    2014-04-01

    A sensitive and specific LC-MS/MS method was developed for simultaneous determination of aloe-emodin, rhein, emodin, chrysophanol and physcion and their conjugates in rat plasma. The lower limit of quantitation of each anthraquinone was 0.020-0.040 µm. Intra-day and inter-day accuracies were 90.1-114.3% and the precisions were anthraquinone was detectable throughout the experimental period (36 h) and showed much higher plasma concentrations and AUC0-t . The free/total ratios of aloe-emodin, rhein and emodin were 6.5, 49.0 and 1.7% for Cmax and 3.7, 32.5 and 1.1% for AUC0-t , respectively. The dose-normalized AUC0-t and Cmax of the total of each anthraquinone were in the same descending order: rhein > emodin > chrysophanol > physcion > aloe-emodin. These findings reveal phase II conjugates as the dominant in vivo existing forms of rhubarb antharquinones and warrant a further study to evaluate their contribution to the herbal activity. Copyright © 2013 John Wiley & Sons, Ltd.

  7. Dosimetry Service

    CERN Multimedia

    2006-01-01

    Cern Staff and Users can now consult their dose records for an individual or an organizational unit with HRT. Please see more information on our web page: http://cern.ch/rp-dosimetry Dosimetry Service is open every morning from 8.30 - 12.00. Closed in the afternoons. We would like to remind you that dosimeters cannot be sent to customers by internal mail. Short-term dosimeters (VCT's) must always be returned to the Service after the use and must not be left on the racks in the experimental areas or in the secretariats. Dosimetry Service Tel. 7 2155 Dosimetry.service@cern.ch http://cern.ch/rp-dosimetry

  8. Safety, Pharmacokinetics and Dosimetry of a Long-Acting Radiolabeled Somatostatin Analogue 177Lu-DOTA-EB-TATE in Patients with Advanced Metastatic Neuroendocrine Tumors.

    Science.gov (United States)

    Zhang, Jingjing; Wang, Hao; Jacobson Weiss, Orit; Cheng, Yuejuan; Niu, Gang; Li, Fang; Bai, Chunmei; Zhu, Zhaohui; Chen, Xiaoyuan

    2018-04-13

    Radiolabeled somatostatin analogue therapy has become an established treatment method for patients with well to moderately differentiated unresectable or metastatic neuroendocrine tumors (NETs). The most frequently used somatostatin analogues in clinical practice are octreotide and octreotate. However, both peptides showed suboptimal retention within tumors. The aim of this first-in-human study is to explore the safety and dosimetry of a long-acting radiolabeled somatostatin analogue, lutetium-177-1, 4, 7, 10-tetra-azacyclododecane-1, 4, 7, 10-tetraacetic acid-Evans blue-octreotate ( 177 Lu-DOTA-EB-TATE). Methods: Eight patients (6 males and 2 females; age range, 27-61 y) with advanced metastatic neuroendocrine tumors were recruited. Five patients received a single dose 0.35-0.70 GBq (9.5-18.9 mCi) of 177 Lu-DOTA-EB-TATE and underwent serial whole body planar and single-photon emission computed tomography-computed tomography (SPECT-CT) scans at 2, 24, 72, 120 and 168 h after injection. The other 3 patients received intravenous injection of 0.28-0.41 GBq (7.5-11.1 mCi) of 177 Lu-DOTATATE for the same imaging acquisition procedures at 1, 3, 4, 24 and 72 h after injection. The dosimetry was calculated using the OLINDA/EXM 1.1 software. Results: Administration of 177 Lu-DOTA-EB-TATE was well tolerated, with no adverse symptoms being noticed or reported in any of the patients. Compared with 177 Lu-DOTATATE, 177 Lu-DOTA-EB-TATE showed extended circulation in the blood and achieved 7.9-fold increase of tumor dose delivery. The total body effective doses were 0.205 ± 0.161 mSv/MBq for 177 Lu-DOTA-EB-TATE and 0.174 ± 0.072 mSv/MBq for 177 Lu-DOTATATE. Significant dose delivery increases to the kidneys and bone marrow were also observed in patients receiving 177 Lu-DOTA-EB-TATE than those receiving 177 Lu-DOTATATE (3.2 and 18.2-fold, respectively). Conclusion: By introducing an albumin binding moiety, 177 Lu-DOTA-EB-TATE showed remarkably higher uptake and retention in NET

  9. Population pharmacokinetic-pharmacodynamic target attainment analysis of imipenem plasma and urine data in neonates and children.

    Science.gov (United States)

    Yoshizawa, Kenichi; Ikawa, Kazuro; Ikeda, Kayo; Ohge, Hiroki; Morikawa, Norifumi

    2013-11-01

    Population pharmacokinetic (PK)-pharmacodynamic target attainment analysis of imipenem was performed to elucidate the PK properties in neonates and children and to rationalize and optimize dosing regimens. Population PK models were separately developed in neonates and children by simultaneously fitting plasma and urine data from 60 neonates and 39 children. The newly developed models were then used to estimate the probability of attaining the pharmacodynamic target (40% of the time above the minimum inhibitory concentration) against clinical isolates of common bacteria in pediatric patients. The data were best described by a 1-compartment model in neonates and a 2-compartment model in children, respectively. Renal clearance in children (0.187 L/h/kg) was double that of neonates (0.0783 L/h/kg), whereas the volume of distribution at steady-state was approximately 1.8-fold larger in neonates (0.466 L/kg) than in children (0.260 L/kg). Age was not a statistically significant covariate in the PK of both groups. Infusions (0.5 h) of 15 mg/kg every 8 h (45 mg/kg/day) and 25 mg/kg every 12 h (50 mg/kg/day) were shown to be sufficient against common bacterial isolates in both patient populations. However, 1.5-h infusions of 25 mg/kg every 8 h (75 mg/kg/day) in neonates and 25 mg/kg every 6 h (100 mg/kg/day) in children were required to be effective against Pseudomonas aeruginosa (minimum inhibitory concentration for 90% of the isolates=16 μg/mL). These results explain the changes in imipenem PK properties during the human growth process and provide guidance for tailoring dosing regimens in each pediatric age group.

  10. Personal dosimetry calculations by means of radio pharmacokinetic and gamma graphic studies; Calculos de dosimetria personalizada por medio de estudios radiofarmacocineticos y gammagraficos

    Energy Technology Data Exchange (ETDEWEB)

    Arteaga de Murphy, C; Ferro F, G; Pedraza L, M; Montoya M, C E [Departamento de Medicina Nuclear, Instituto Nacional de Ciencias Medicas y Nutricion, Vasco de Quiroga 15, 14000 Mexico D.F. (Mexico)

    2000-07-01

    The determination of the absorbed radiation dose is an essential factor to assess the risk to patient with a diagnostic study of nuclear medicine but over all it is indispensable for predicting the efficiency of individualized radio pharmacotherapy and weighting up the risk/benefit of the treatment. In studies for diagnostic or/and treatment of nuclear medicine generally the absorbed radiation dose is not determined for each patient since the methods for estimating it are laborious and include complex models such biological as mathematical, therefore is very important to have a relatively easy method. The obtained data with {sup 99m} Tc-Abp., a new radiopharmaceutical for osseous gammagraphy, were used with the purpose of exemplifying a practical method. The radio pharmacokinetic parameters were determined during 24 hours in 10 health voluntaries and serial gamma grams were taken during two hours to another voluntaries. The obtained data were used to estimate, with the MIRDOSE3 computer program, the absorbed radiation dose in an osseous dragging with {sup 99m} Tc-Abp. is low: 0.00472 m Gy/MBq to osseous marrow, mainly to the vertebral column and femur, and 0.00169 m Gy/ MBq to whole body. These data are lower than those informed in the medical literature for other bis phosphonates. (Author)

  11. Pharmacokinetics, biodistribution and dosimetry of sup 99 Tc sup m (V)DMSA in humans with squamous cell carcinoma. [Dimercaptosuccinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Watkinson, J.C.; Allen, S.; Lazarus, C.R.; Sinclair, J.; Blake, G.M.; Clarke, S.E.M. (Guy' s Hospital, London (UK))

    1990-05-01

    Technetium-99m ({sup 99}Tc{sup m})(V) dimercaptosuccinic acid (DMSA) is a new tumour imaging agent which has been used to evaluate squamous carcinoma (SCC) of the head and neck. This study evaluated the pharmacokinetics and biodistribution of {sup 99}Tc{sup m}(V)DMSA in patients with SCC and calculated the bone mass of a New Zealand White (NZW) rabbit. This data was then used to calculate the effective dose equivalent in man. A total of 16 patients were studied (5 with no tumour, 11 with tumour). {sup 99}Tc{sup m}(V)DMSA had a fast bi-exponential blood clearance in patients with no tumour (30 and 401 min) and patients with tumour (30 and 387 min) with no significant difference (p > 0.05) between the two groups. {sup 99}Tc{sup m}(V)DMSA had a fast cumulative urine excretion with mean half-times in non-tumour and tumour patients of 183 min and 244 min respectively. There was no significant difference (p > 0.05) between these two latter groups. The effective dose equivalent of {sup 99}Tc{sup m}(V)DMSA in man is 5.1 {mu}Sv/MBq. (author).

  12. Determination of Acyclovir in Human Plasma Samples by HPLC Method with UV Detection: Application to Single-Dose Pharmacokinetic Study

    Directory of Open Access Journals (Sweden)

    Dragica Zendelovska

    2015-03-01

    CONCLUSION: Good precision, accuracy, simplicity, sensitivity and shorter time of analysis of the method makes it particularly useful for processing of multiple samples in a limited period of time for pharmacokinetic study of acyclovir.

  13. Determination of Doxorubicin in Stealth Hyalurionic Acid-Based Nanoparticles in Rat Plasma by the Liquid-Liquid Nanoparticles-Breaking Extraction Method: Application to a Pharmacokinetic Study.

    Science.gov (United States)

    Han, Xiaopeng; Wei, Wei; Zhong, Lu; Luo, Cong; Wu, Chunnuan; Jiang, Qikun; Sun, Jin

    2016-09-01

    An efficient extraction of doxorubicin (Dox) from homemade stealth hyalurionic acid (HA)-based nanoparticles (NPs) in rat plasma could not be performed by previously published methods. Therefore, we attempted to establish the novel NPs-breaking and UPLC-MS-MS method for evaluating the pharmacokinetic profiles of the homemade stealth HA NPs in rats. The pretreatment method of plasma samples used the liquid-liquid extraction method with isopropyl alcohol as NPs-breaking and protein-precipitating solvents, and the NPs-breaking efficiency of isopropyl alcohol was as high as 97.2%. The analyte and gliclazide (internal standard) were extracted from plasma samples with isopropyl alcohol and were separated on UPLC BEH C18 with a mobile phase consisting of methanol and water (containing 0.1% formic acid). The method demonstrated good linearity at the concentrations ranging from 5 to 5,000 ng/mL. The intra- and interday relative standard deviations were >10%. Finally, the method was successfully applied to a pharmacokinetic study of homemade stealth HA-based NPs in rats following intravenous administration. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Simultaneous Determination of Multiple Components in Guanjiekang in Rat Plasma via the UPLC–MS/MS Method and Its Application in Pharmacokinetic Study

    Directory of Open Access Journals (Sweden)

    Jian Wu

    2016-12-01

    Full Text Available Guanjiekang (GJK that is formed by five medicinal herbs including Astragali Radix, Aconiti Lateralis Radix Praeparaia, Glycyrrhizae Radix et Rhizoma, Corydalis Rhizoma and Paeoniae Radix Alba was used for the treatment of rheumatoid arthritis (RA. However, the pharmacokinetic (PK profile of active components in GJK remains unclear. This study aims to evaluate the pharmacokinetic behavior of seven representative active constituents in GJK (i.e., benzoylhypaconine, benzoylmesaconine, paeoniflorin, tetrahydropalmatine, calycosin-7-glucoside, formononetin and isoliquiritigenin after oral administration of GJK in rats. A rapid, sensitive and reliable ultra-performance liquid chromatography-tandem mass spectrometer (UPLC–MS/MS method has been successfully developed for the simultaneous determination of these seven constituents in rat plasma. Chromatographic separation was achieved on a C18 column with a gradient elution program that consists of acetonitrile and water (containing 0.1% formic acid at a flow rate of 0.35 mL/min. Detection was performed under the multiple reaction monitoring (MRM in the positive electrospray ionization (ESI mode. The calibration curves exhibited good linearity (R2 > 0.99 over a wide concentration range for all constituents. The accuracies ranged from 92.9% to 107.8%, and the intra-day and inter-day precisions at three different levels were below 15%. Our PK results showed that these seven compounds were quickly absorbed after the administration of the GJK product, and Tmax ranged from 30 min to 189 min. The in vivo concentrations of paeoniflorin and isoliquiritigenin were significantly higher than the reported in vitro effective doses, indicating that they could partly contribute to the therapeutic effect of GJK. Therefore, we conclude that pharmacokinetic studies of representative bioactive chemicals after administration of complex herbal products are not only necessary but also feasible. Moreover, these seven

  15. Determination of 6258-70, a new semi-synthetic taxane, in rat plasma and tissues: Application to the pharmacokinetics and tissue distribution study

    Directory of Open Access Journals (Sweden)

    Simin Zhao

    2016-08-01

    Full Text Available Cancer is the leading cause of death all over the world. Among the chemotherapy drugs, taxanes play an important role in cancer treatment. 6258-70 is a new semi-synthetic taxane which has a broad spectrum of antitumor activity. A fast and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS method was developed for quantification of 6258-70 in rat plasma and tissues in this paper. After extraction by liquid-liquid extraction method with methyl tert-butyl ether, the samples were separated on a Kinetex C18 column (50 mm×2.1 mm, 2.6 µm, Phenomenex, USA within 3 min. The method was fully validated with the matrix effect between 87.7% and 99.5% and the recovery ranging from 80.3% to 90.1%. The intra- and inter-day precisions were less than 9.5% and the accuracy ranged from −3.8% to 6.5%. The reliable method was successfully applied to the pharmacokinetics and tissue distribution studies of 6258-70 after intravenous administration in rats. The pharmacokinetic results indicated that the pharmacokinetic behavior of 6258-70 in rats was in accordance with linear features within tested dosage of 1 to 4 mg/kg, and there was no significant difference between the two genders. The tissue distribution study showed that 6258-70 had an effective penetration, spread widely and rapidly and could cross blood-brain barrier. The results of pharmacokinetics and tissue distribution may provide a guide for future study.

  16. A simple and sensitive method for determination of vitamins D3 and K1 in rat plasma: application for an in vivo pharmacokinetic study.

    Science.gov (United States)

    Gershkovich, Pavel; Ibrahim, Fady; Sivak, Olena; Darlington, Jerald W; Wasan, Kishor M

    2014-03-01

    To develop and to validate a simple but sensitive method for determination of vitamins D3 and K1 in rat plasma. The sample treatment included protein precipitation by cold acetonitrile, evaporation, reconstitution with methanol and filtration. The chromatography conditions included Xterra RP18 3.5 µm 4.6 × 100 mm column at ambient temperature and mobile phase consisting of methanol/water (93/7, v/v) at 0.5 mL/min flow rate. Vitamin D3 and probucol were detected at 265 nm and vitamin K1 at 239 nm. Rats were administered intravenously by 0.1 mg/kg of vitamin D3 or K1 and the blood samples were withdrawn pre-administration and at pre-determined time points post-administration. The pharmacokinetic analysis was performed using a non-compartmental approach. The calibration curves in rat plasma were linear up to 5000 ng/mL for both vitamins. The limit of quantification (LOQ) was 20 ng/mL for vitamin D3 and 40 ng/mL for K1. Inter- and intra-day precision and accuracy were below 15%. The pharmacokinetic parameters of vitamin D3 following intravenous administration were: AUC0-∞ = 11323 ± 1081 h × ng/mL, Vd = 218 ± 80 mL/kg, CL = 8.9 ± 0.8 mL/h/kg, t1/2 = 16.8 ± 5 h; and of vitamin K1: AUC0-∞ = 2495 ± 297 h × ng/mL, Vd = 60 ±24 mL/kg, CL = 40.5 ± 5.1 mL/h/kg, t1/2 = 1.1 ±0.5 h. The developed HPLC-UV assay is a simple and sensitive method for the determination of vitamins D3 and K1 in rat plasma. A higher dose of vitamin K1 should be used in future studies for accurate estimation of pharmacokinetic parameters. The data show the suitability of the assay for pharmacokinetic studies in rats.

  17. Comparative pharmacokinetic profiles of tectorigenin in rat plasma by UPLC-MS/MS after oral administration of Iris tectorum Maxim extract and pure tectoridin.

    Science.gov (United States)

    Yang, Min; Yang, Xiaolin; An, Jinmeng; Xiao, Wei; Wang, Zhenzhong; Huang, Wenzhe; Yang, Zhonglin; Li, Fei

    2015-10-10

    Iris tectorum Maxim, a well-known herb medicine, is commonly used for treatment of inflammation, cough, and pharyngitis for a long time in China. Tectoridin, main active ingredient of Iris tectorum Maxim, is often used for its quality control. This study was aimed to analyze the pharmacokinetic profile of tectorigenin (the metabolite of tectoridin) after oral administration of I. tectorum Maxim extract, and to compare the pharmacokinetic characterization of tectorigenin after oral administration of I. tectorum Maxim extract (ITME) and pure tectoridin (PT) in rats. In addition, a simple, reliable and sensitive UPLC-MS/MS method was developed for determination of tectorigenin in rat plasma, using kaempferol as internal standard. The processed samples were separated on a Poroshell 120 SB-C₁₈ column and detected by positive electrospray ionization in multiple reaction monitoring (MRM) mode. The method validation results indicated that the established method was simple, specific and reliable. The pharmacokinetic results showed that the plasma concentration of tectorigenin in ITME group was much higher than that of the PT group (p<0.01). Moreover, compared to PT group, t₁/₂ value and AUC(0-∞) value were also notably increased in ITME group (p<0.01). In conclusion, potential interaction exists between those chemical components in ITME, and the co-existing components in ITME could notably promote the absorption of tectoridin in rats, however, the exact compound(s) which enhance the absorption of tectoridin should be investigated in future study. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. LC-MS/MS Determination and Pharmacokinetic Study of Pedunculoside in Rat Plasma after Oral Administration of Pedunculoside and Ilex rotunda Extract

    Directory of Open Access Journals (Sweden)

    Waiou Zhao

    2015-05-01

    Full Text Available Ilex rotunda is widely used to treat many disorders as a traditional Chinese medicine (TCM containing 4%–5% pedunculoside (PDC. A rapid, selective, and sensitive liquid chromatography-tandem mass spectrometry method (LC-MS/MS was developed and validated to determine PDC in rat plasma by using 3β,19α-dihydroxyurs-12-en-28-oic acid 28-β-D-glucopyranosyl ester (DEOG as an internal standard. The analytes were extracted by protein precipitation and eluted on a C18 chromatography column using a mobile phase of methanol–H2O (70:30, v/v delivered at a flow rate of 0.6 mL/min. Detection was performed using positive ion electrospray ionization in multiple reaction monitoring modes. The assay was linear over the concentration range of 0.60 ng/mL to 200 ng/mL, with a quantification limit of 0.60 ng/mL. Intra-day and inter-day precisions (%RSD ranged from 2.12 to 9.51 for PDC, whereas the accuracy was within −7.83%~9.40%. The validated method was successfully applied to the pharmacokinetic study of PDC in rat plasma after oral administration of pure PDC and Ilex rotunda extract (IRE. Pharmacokinetic parameters of PDC in IRE, such as Cmax, AUC0–t, AUC0–∞, t1/2z, and CLz/F, statistically differed from those of the pure monomer (p < 0.01. However, Tmax and MRT showed no significant differences between the two groups. Results suggested that other coexisting components in IRE may decrease the absorption of PDC. Compound-compound interactions between PDC and other herbal extract components can alter the pharmacokinetic behavior of PDC. The study will be helpful in providing references for understanding the action mechanism and clinical application of Ilex rotunda.

  19. A validated high-performance liquid chromatographic method for the determination of glibenclamide in human plasma and its application to pharmacokinetic studies.

    Science.gov (United States)

    Niopas, Ioannis; Daftsios, Athanasios C

    2002-05-15

    Glibenclamide is a potent second generation oral sulfonylurea antidiabetic agent widely used for the treatment of type II diabetes melitus. A rapid, sensitive, precise, accurate and specific HPLC assay for the determination of glibenclamide in human plasma was developed and validated. After addition of flufenamic acid as internal standard, the analytes were isolated from human plasma by liquid-liquid extraction. The method was linear in the 10-400 ng/ml concentration range (r > 0.999). Recovery for glibenclamide was greater than 91.5% and for internal standard was 93.5%. Within-day and between-day precision, expressed as the relative standard deviation (RSD%), ranged from 1.4 to 5.9% and 5.8 to 6.6%, respectively. Assay accuracy was better than 93.4%. The assay was used to estimate the pharmacokinetics of glibenclamide after oral administration of a 5 mg tablet of glibenclamide to 18 healthy volunteers.

  20. Ultra-performance liquid chromatography-tandem mass spectrometry method for the determination of febuxostat in dog plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Zhang, Tianhong; Sun, Yuanpeng; Zhang, Peng; Gao, Jingmei; Wang, Shanshan; He, Zhonggui

    2013-02-01

    A rapid, sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the determination of febuxostat in dog plasma. Using paclitaxel as an internal standard (IS), a simple liquid-liquid extraction method with ethyl acetate was adopted for plasma sample pretreatment. Separation was carried out on an Acquity UPLC BEH C(18) column with a mobile phase consisting of acetonitrile and water (containing 0.2% formic acid). The assay was linear in the concentration ranged from 5 to 5000 ng/mL with a lower limit of quantification of 5 ng/mL for febuxostat. The single run analysis was as short as 2.0 min. Finally, the developed method was successfully applied to the pharmacokinetic study of febuxostat tablets following oral administration at a single dose of 40 mg in beagle dogs. Copyright © 2012 John Wiley & Sons, Ltd.

  1. A Wide Linearity Range Method for the Determination of Lenalidomide in Plasma by High-Performance Liquid Chromatography: Application to Pharmacokinetic Studies.

    Science.gov (United States)

    Guglieri-López, Beatriz; Pérez-Pitarch, Alejandro; Martinez-Gómez, Maria Amparo; Porta-Oltra, Begoña; Climente-Martí, Mónica; Merino-Sanjuán, Matilde

    2016-12-01

    A wide linearity range analytical method for the determination of lenalidomide in patients with multiple myeloma for pharmacokinetic studies is required. Plasma samples were ultrasonicated for protein precipitation. A solid-phase extraction was performed. The eluted samples were evaporated to dryness under vacuum, and the solid obtained was diluted and injected into the high-performance liquid chromatography (HPLC) system. Separation of lenalidomide was performed on an Xterra RP C18 (250 mm length × 4.6 mm i.d., 5 µm) using a mobile phase consisting of phosphate buffer/acetonitrile (85:15, v/v, pH 3.2) at a flow rate of 0.5 mL · min -1 The samples were monitored at a wavelength of 311 nm. A linear relationship with good correlation coefficient (r = 0.997, n = 9) was found between the peak area and lenalidomide concentrations in the range of 100 to 950 ng · mL -1 The limits of detection and quantitation were 28 and 100 ng · mL -1 , respectively. The intra- and interassay precisions were satisfactory, and the accuracy of the method was proved. In conclusion, the proposed method is suitable for the accurate quantification of lenalidomide in human plasma with a wide linear range, from 100 to 950 ng · mL -1 This is a valuable method for pharmacokinetic studies of lenalidomide in human subjects. © 2016 Society for Laboratory Automation and Screening.

  2. Plasma exogenous creatinine excretion for the assessment of renal function in avian medicine--pharmacokinetic modeling in racing pigeons (Columba livia).

    Science.gov (United States)

    Scope, Alexandra; Schwendenwein, Ilse; Schauberger, Günther

    2013-09-01

    The diagnostic evaluation of the glomerular filtration rate by urinary clearance has significant practical limitations in birds because urine is excreted together with feces. Thus, pharmacokinetic modeling of an exogenous plasma creatinine clearance could be useful for assessing renal creatinine excretion in birds. For this study, creatinine (50 mg/kg) was administered to 2 groups of 15 pigeons (Columba livia) each; in one group by the intravenous (IV) route and in the second by the intramuscular (IM) route. The time series of the plasma creatinine concentrations were analyzed by pharmacokinetic models. Body mass-specific creatinine excretion was determined for IV and IM administration to be between 6.30 and 6.44 mL/min per kg, respectively. Body surface area-specific creatinine clearance, which is related to the metabolic rate, was calculated between 0.506 and 0.523 mL/min per dm2, respectively. The results showed that IV as well as IM administration can be used for assessing renal creatinine excretion in pigeons. For practical reasons, IM administration is recommended, with the use of the Bateman function to calculate creatinine elimination.

  3. Determination and Pharmacokinetic Study of Three Diterpenes in Rat Plasma by UHPLC-ESI-MS/MS after Oral Administration of Rosmarinus officinalis L. Extract

    Directory of Open Access Journals (Sweden)

    Liqian Wang

    2017-06-01

    Full Text Available Rosmarinus officinalis L. is commonly used as a spice and flavoring agent. Diterpenes are the main active compounds of R. officinalis. An Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-ESI-MS/MS method was developed for the determination of carnosol, rosmanol, and carnosic acid isolated from R. officinalis in rat plasma, and applied to a pharmacokinetic study after oral administration of R. officinalis extract. Sample preparation involved a liquid-liquid extraction of the analytes with ethyl acetate. Butylparaben was employed as an internal standard (I.S.. Chromatographic separation was carried out on a C18 column (ACQUITY UPLC® HSS T3, 1.8 μm, 2.1 mm × 100 mm with a gradient system consisting of the mobile phase solution A (0.1% formic acid in water and solution B (acetonitrile at the flow rate of 0.3 mL/min. The quantification was obtained using multiple reaction monitoring (MRM mode with electrospray ionization (ESI. The UHPLC-MS/MS assay was validated for linearity, accuracy, precision, extraction recovery, matrix effect and stability. This study described a simple, sensitive and validated UHPLC-MS/MS method for the simultaneous determination of three diterpene compounds in rat plasma after oral administration of R. officinalis extract, and investigated on their pharmacokinetic studies as well.

  4. Development of a UPLC-ESI-MS/MS method for the determination of larotaxel in beagle dog plasma: application to the pharmacokinetic study.

    Science.gov (United States)

    Liu, Zhenzhen; Zhang, Bo; Liu, Zhihong; Li, Song; Li, Guofei; Geng, Lulu; Zhao, Xu; Bi, Kaishun; Tang, Xing; Chen, Xiaohui

    2012-04-01

    A UPLC-ESI-MS/MS method has been developed and validated for the determination of larotaxel in beagle dog plasma. After addition of the internal standard, plasma samples were extracted by liquid-liquid extraction with methyl tert-butyl ether and separated on a 50×2.1 mm ACQUITY 1.7 μm C18 column (Waters, USA), with acetonitrile and 5 mM ammonium acetate as mobile phase, within a runtime of 3.0 min. The analytes were detected without interference in Multiple Reaction Monitoring mode with positive electrospray ionization. The linear range was 2.5-5,000 ng/mL. The intra-day and inter-day precisions (relative standard deviation, RSD, %) were within 9.3% and 10.2%, respectively, and the accuracy (relative error, RE, %) was less than 11.5%. The validated method was successfully applied to a pharmacokinetic study of larotaxel in beagle dogs after intravenous administration of larotaxel-loaded lipid microsphere with different doses of 0.4, 0.8, and 1.6 mg/kg. The area under the concentration-time curve and the peak concentration of larotaxel seemed to increase with increasing dose proportionally, suggesting linear pharmacokinetics.

  5. Simultaneous quantification of multiple components in rat plasma by UPLC-MS/MS and pharmacokinetic study after oral administration of Huangqi decoction.

    Science.gov (United States)

    Zeng, Jia-Kai; Li, Yuan-Yuan; Wang, Tian-Ming; Zhong, Jie; Wu, Jia-Sheng; Liu, Ping; Zhang, Hua; Ma, Yue-Ming

    2018-05-01

    A rapid, sensitive and accurate UPLC-MS/MS method was developed for the simultaneous quantification of components of Huangqi decoction (HQD), such as calycosin-7-O-β-d-glucoside, calycosin-glucuronide, liquiritin, formononetin-glucuronide, isoliquiritin, liquiritigenin, ononin, calycosin, isoliquiritigenin, formononetin, glycyrrhizic acid, astragaloside IV, cycloastragenol, and glycyrrhetinic acid, in rat plasma. After plasma samples were extracted by protein precipitation, chromatographic separation was performed with a C 18 column, using a gradient of methanol and 0.05% acetic acid containing 4mm ammonium acetate as the mobile phase. Multiple reaction monitoring scanning was performed to quantify the analytes, and the electrospray ion source polarity was switched between positive and negative modes in a single run of 10 min. Method validation showed that specificity, linearity, accuracy, precision, extraction recovery, matrix effect and stability for 14 components met the requirements for their quantitation in biological samples. The established method was successfully applied to the pharmacokinetic study of multiple components in rats after intragastric administration of HQD. The results clarified the pharmacokinetic characteristics of multiple components found in HQD. This research provides useful information for understanding the relation between the chemical components of HQD and their therapeutic effects. Copyright © 2017 John Wiley & Sons, Ltd.

  6. A Study on Pharmacokinetics of Bosentan with Systems Modeling, Part 1: Translating Systemic Plasma Concentration to Liver Exposure in Healthy Subjects.

    Science.gov (United States)

    Li, Rui; Niosi, Mark; Johnson, Nathaniel; Tess, David A; Kimoto, Emi; Lin, Jian; Yang, Xin; Riccardi, Keith A; Ryu, Sangwoo; El-Kattan, Ayman F; Maurer, Tristan S; Tremaine, Larry M; Di, Li

    2018-04-01

    Understanding liver exposure of hepatic transporter substrates in clinical studies is often critical, as it typically governs pharmacodynamics, drug-drug interactions, and toxicity for certain drugs. However, this is a challenging task since there is currently no easy method to directly measure drug concentration in the human liver. Using bosentan as an example, we demonstrate a new approach to estimate liver exposure based on observed systemic pharmacokinetics from clinical studies using physiologically based pharmacokinetic modeling. The prediction was verified to be both accurate and precise using sensitivity analysis. For bosentan, the predicted pseudo steady-state unbound liver-to-unbound systemic plasma concentration ratio was 34.9 (95% confidence interval: 4.2, 50). Drug-drug interaction (i.e., CYP3A and CYP2B6 induction) and inhibition of hepatic transporters (i.e., bile salt export pump, multidrug resistance-associated proteins, and sodium-taurocholate cotransporting polypeptide) were predicted based on the estimated unbound liver tissue or plasma concentrations. With further validation and refinement, we conclude that this approach may serve to predict human liver exposure and complement other methods involving tissue biopsy and imaging. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  7. Simultaneous determination of atorvastatin, metformin and glimepiride in human plasma by LC–MS/MS and its application to a human pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Srinivasa Rao Polagani

    2013-02-01

    Full Text Available A simple, rapid and sensitive liquid chromatography-tandem mass spectrometric (LC–MS/MS assay method has been developed and fully validated for the simultaneous quantification of atorvastatin, metformin and glimepiride in human plasma. Carbamazepine was used as internal standard (IS. The analytes were extracted from 200 μL aliquots of human plasma via protein precipitation using acetonitrile. The reconstituted samples were chromatographed on a Alltima HP C18 column by using a 60:40 (v/v mixture of acetonitrile and 10 mM ammonium acetate (pH 3.0 as the mobile phase at a flow rate of 1.1 mL/min. The calibration curves obtained were linear (r2≥0.99 over the concentration range of 0.50–150.03 ng/mL for atorvastatin, 12.14–1207.50 ng/mL for metformin and 4.98–494.29 ng/mL for glimepiride. The API-4000 LC–MS/MS in multiple reaction monitoring (MRM mode was used for detection. The results of the intra- and inter-day precision and accuracy studies were well within the acceptable limits. All the analytes were found to be stable in a battery of stability studies. The method is precise and sensitive enough for its intended purpose. A run time of 2.5 min for each sample made it possible to analyze more than 300 plasma samples per day. The developed assay method was successfully applied to a pharmacokinetic study in human male volunteers. Keywords: Atorvastatin, Metformin, Glimepiride, LC–MS/MS, Human plasma, Pharmacokinetics

  8. Acamprosate determinations in plasma and cerebrospinal fluid after multiple dosing measured by liquid chromatography-mass spectroscopy: a pharmacokinetic study in healthy volunteers.

    Science.gov (United States)

    Hammarberg, Anders; Beck, Olof; Eksborg, Staffan; Jayaram-Lindström, Nitya; Lindefeldt, Annika; Andersson, Maria; Brundin, Lou; Reid, Malcolm S; Franck, Johan

    2010-08-01

    The central nervous system-active medication acamprosate has been shown to modulate alcohol-related behavior in both preclinical and clinical studies. Although commonly used in the treatment of alcohol dependence, there are still unanswered questions concerning the pharmacokinetic properties of acamprosate. The aims of the present study were to 1) to validate liquid chromatography-mass spectrometry as a method to study the presence of acamprosate in plasma and cerebrospinal fluid (CSF) in humans; and 2) validate previous results on clinically important pharmacokinetic data for acamprosate. In an open label, single-site design, 13 healthy males and females were recruited to 22 days of oral acamprosate treatment (1998 mg/day). Subjects provided in all 256 plasma samples for analysis at regular intervals at Day 1, 7, 14, and 22 of treatment. On Day 22, subjects also left a sample of CSF for measurement of acamprosate. The results showed that steady-state level of acamprosate was accomplished within 5 days after the start of treatment and remained fairly stable for 2 to 3 days after termination of treatment. Variations in plasma concentrations corresponded to earlier studies and did not exceed those for comparable pharmacotherapeutic agents. Acamprosate concentrations in the CSF were below the limit of quantification, ie, estimated concentrations between 9 and 33 ng/mL. Plasma concentrations were more than 25 times higher than in lumbar CSF. The low CSF levels seen after 3 weeks of treatment may provide an explanation to the delay in therapeutic effect noticed in treatment studies on acamprosate. A longer duration of treatment might be necessary to obtain clinically significant brain levels of acamprosate. In summary, the present study validated liquid chromatography-mass spectrometry as a method for assessment of compliance to acamprosate treatment. Furthermore, the results suggest that the mechanism of action of acamprosate needs to be further explored with regard to

  9. ESR Dosimetry

    International Nuclear Information System (INIS)

    Baffa, Oswaldo; Rossi, Bruno; Graeff, Carlos; Kinoshita, Angela; Chen Abrego, Felipe; Santos, Adevailton Bernardo dos

    2004-01-01

    ESR dosimetry is widely used for several applications such as dose assessment in accidents, medical applications and sterilization of food and other materials. In this work the dosimetric properties of natural and synthetic Hydroxyapatite, Alanine, and 2-Methylalanine are presented. Recent results on the use of a K-Band (24 GHz) ESR spectrometer in dosimetry are also presented

  10. Dosimetry Service

    CERN Multimedia

    2005-01-01

    Please remember to read your dosimeter at least once a month. Regular read-outs are vital to ensure that your personal dose is periodically monitored. Dosimeters should be read even if you have not visited the controlled areas. Dosimetry Service - Tel. 7 2155 http://cern.ch/rp-dosimetry

  11. Dosimetry Service

    CERN Multimedia

    Dosimetry Service

    2005-01-01

    Please remember to read your dosimeter at least once a month. Regular read-outs are vital to ensure that your personal dose is periodically monitored. Dosimeters should be read even if you have not visited the controlled areas. Dosimetry Service Tel. 7 2155 http://cern.ch/rp-dosimetry

  12. Dosimetry Service

    CERN Multimedia

    2005-01-01

    Please remember to read your dosimeter at least once a month. Regular read-outs are vital to ensure that your personal dose is periodically monitored. Dosimeters should be read even if you have not visited the controlled areas. Dosimetry Service - Tel. 72155 http://cern.ch/rp-dosimetry

  13. An HPLC tandem mass spectrometry for quantification of ET-26-HCl and its major metabolite in plasma and application to a pharmacokinetic study in rats.

    Science.gov (United States)

    Chen, Xu; Zhang, Wensheng; Rios, Sandy; Morkos, Miriam B; Ye, Xiaoli; Li, Gen; Jiang, Xuehua; Wang, Zhijun; Wang, Ling

    2018-02-05

    ET-26-HCl is a new analog of etomidate, a short-acting anesthetic drug, with less adrenal cortex inhibition. The pharmacokinetics of ET-26-HCl in rats needs to be determined for future clinical trials in human subjects. In order to facilitate the pharmacokinetic study, a liquid chromatography based tandem mass spectrometric (HPLC-MS/MS) method was developed and validated for quantification of ET-26-HCl and its major metabolite, ET-26-acid. These two compounds and gabapentin (internal standard) were extracted using a protein precipitation method with methanol and detected by Multiple Reaction Monitoring of m/z transition of 275.6-170.9, 217.7-113.1, and 172.5-154.3 for ET-26-HCl, ET-26-acid, and gabapentin respectively. This method was validated in terms of sensitivity, linearity, reproducibility, and stability. The HPLC-MS/MS method was found linear over the concentration ranges of 21.76-4352ng/mL, and 18.62-3724ng/mL with LLOQ of 21.76 and 18.62ng/mL for ET-26-HCl and ET-26-acid respectively. The mean intra-day and inter-day accuracy was between 94.11-107.78%, while the precision was within the limit of 15.0% for all the quality control samples. A pharmacokinetic study was then conducted in rats following intravenous injection of 2.1, 4.2, and 8.4mg/kg. The linear pharmacokinetics of ET-26-HCl was observed over the dose range of 2.1-8.4mg/kg. The average terminal phase elimination half-lives were 0.87 and 1.03h for ET-26-HCl and ET-26-acid respectively. In summary, an HPLC-MS/MS method for quantification of ET-26-HCl in rat plasma has been developed and successfully applied to a pharmacokinetic study. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. A paradigm shift in pharmacokinetic-pharmacodynamic (PKPD) modeling: rule of thumb for estimating free drug level in tissue compared with plasma to guide drug design.

    Science.gov (United States)

    Poulin, Patrick

    2015-07-01

    A basic assumption in pharmacokinetics-pharmacodynamics research is that the free drug concentration is similar in plasma and tissue, and, hence, in vitro plasma data can be used to estimate the in vivo condition in tissue. However, in a companion manuscript, it has been demonstrated that this assumption is violated for the ionized drugs. Nonetheless, these observations focus on in vitro static environments and do not challenge data with an in vivo dynamic system. Therefore, an extension from an in vitro to an in vivo system becomes the necessary next step. The objective of this study was to perform theoretical simulations of the free drug concentration in tissue and plasma by using a physiologically based pharmacokinetics (PBPK) model reproducing the in vivo conditions in human. Therefore, the effects of drug ionization, lipophilicity, and clearance have been taken into account in a dynamic system. This modeling exercise was performed as a proof of concept to demonstrate that free drug concentration in tissue and plasma may also differ in a dynamic system for passively permeable drugs that are ionized at the physiological pH. The PBPK model simulations indicated that free drug concentrations in tissue cells and plasma significantly differ for the ionized drugs because of the pH gradient effect between cells and interstitial space. Hence, a rule of thumb for potentially performing more accurate PBPK/PD modeling is suggested, which states that the free drug concentration in tissue and plasma will differ for the ionizable drugs in contrast to the neutral drugs. In addition to the pH gradient effect for the ionizable drugs, lipophilicity and clearance effects will increase or decrease the free drug concentration in tissue and plasma for each class of drugs; thus, higher will be the drug lipophilicity and clearance, lower would be the free drug concentration in plasma, and, hence, in tissue, in a dynamic in vivo system. Therefore, only considering the value of free

  15. Precolumn derivatization LC–MS/MS method for the determination and pharmacokinetic study of glucosamine in human plasma and urine

    Directory of Open Access Journals (Sweden)

    Min Song

    2012-02-01

    Full Text Available A selective precolumn derivatization liquid chromatography–tandem mass spectrometric (LC–MS/MS method for the determination of glucosamine in human plasma and urine has been developed and validated. Glucosamine was derivatized by o-phthalaldehyde/3-mercaptopropionic acid. Chromatographic separation was performed on a Phenomenex ODS column (150 mm×4.6 mm, 5 μm using linear gradient elution by a mobile phase consisting of methanol (A, and an aqueous solution containing 0.2% ammonium acetate and 0.1% formic acid (B at a flow rate of 1 mL/min. Tolterodine tartrate was used as the internal standard (IS. With protein precipitation by acetonitrile and then the simple one-step derivatization, a sensitive bio-assay was achieved with the lower limit of quantitation (LLOQ as low as 12 ng/mL for plasma. The standard addition calibration curves suitable for clinical sample analysis showed good linearity over the range of 0.012–8.27 μg/mL in plasma and 1.80–84.1 μg/mL in urine. The fully validated method has been successfully applied to a pharmacokinetic study of compound glucosamine sulfate dispersible tablets in health Chinese volunteers receiving single oral doses at 500, 1000 and 1500 mg of glucosamine sulfate, as well as multiple oral doses of 500 mg t.i.d. for 7 consecutive days. Keywords: Glucosamine, Pharmacokinetics, Precolumn derivatization, LC–MS/MS

  16. Human plasma metabolic profiles of benzydamine, a flavin-containing monooxygenase probe substrate, simulated with pharmacokinetic data from control and humanized-liver mice.

    Science.gov (United States)

    Yamazaki-Nishioka, Miho; Shimizu, Makiko; Suemizu, Hiroshi; Nishiwaki, Megumi; Mitsui, Marina; Yamazaki, Hiroshi

    2018-02-01

    1. Benzydamine is used clinically as a nonsteroidal anti-inflammatory drug in oral rinses and is employed in preclinical research as a flavin-containing monooxygenase (FMO) probe substrate. In this study, plasma concentrations of benzydamine and its primary N-oxide and N-demethylated metabolites were investigated in control TK-NOG mice, in humanized-liver mice, and in mice whose liver cells had been ablated with ganciclovir. 2. Following oral administration of benzydamine (10 mg/kg) in humanized-liver TK-NOG mice, plasma concentrations of benzydamine N-oxide were slightly higher than those of demethyl benzydamine. In contrast, in control and ganciclovir-treated TK-NOG mice, concentrations of demethyl benzydamine were slightly higher than those of benzydamine N-oxide. 3. Simulations of human plasma concentrations of benzydamine and its N-oxide were achieved using simplified physiologically based pharmacokinetic models based on data from control TK-NOG mice and from reported benzydamine concentrations after low-dose administration in humans. Estimated clearance rates based on data from humanized-liver and ganciclovir-treated TK-NOG mice were two orders magnitude high. 4. The pharmacokinetic profiles of benzydamine were different for control and humanized-liver TK-NOG mice. Humanized-liver mice are generally accepted human models; however, drug oxidation in mouse kidney might need to be considered when probe substrates undergo FMO-dependent drug oxidation in mouse liver and kidney.

  17. On the search for new anticancer drugs 14: the plasma pharmacokinetics and tissue distribution of spin-labeled thio-TEPA (SL-O-TT).

    Science.gov (United States)

    Gutierrez, P L; Cohen, B E; Sosnovsky, G; Davis, T A; Egorin, M J

    1985-01-01

    We defined the plasma and tissue concentrations and pharmacokinetics of SL-O-TT, a spin-labeled analog of thio-TEPA, in 35-44-g male Swiss Webster mice that had received spin-labeled thio-TEPA at a dosage of 10 mg/kg. Concentrations of spin-labeled thio-TEPA in ethyl acetate extracts of tissue and plasma were determined by gas-liquid chromatography and electron spin resonance spectroscopy. Plasma concentrations of spin-labeled thio-TEPA declined in a biexponential fashion that was well described by the equation: Ct = 21.5e-0.276t + 2.30e-0.026t indicating a half-life alpha of 2.5 min and a half-life beta of 26.6 min. After 2 h there was still spin-labeled thio-TE-PA in plasma, but not in tissues. In tissues, no spin-labeled thio-TEPA was detected with gas-liquid chromatography 15 min after injection, but with electron-spin resonance label was found in lung and skeletal muscle. The main metabolite of spin-labeled thio-TEPA is spin-labeled TEPA, where oxidative desulfurization is invoked as the main metabolic mechanism. Reduction of the spin label to the hydroxylamine was also observed with time.

  18. High-performance liquid chromatographic method for the determination of nicardipine in pure, pharmaceutical preparations and plasma and its application to pharmacokinetics in humans

    Directory of Open Access Journals (Sweden)

    Sheikha M. Al-Ghannam

    2009-01-01

    Full Text Available A simple, sensitive and reproducible reversed-phase liquid chromatographic method has been developed and validated for the determination of nicardipine hydrochloride (NC in pure, pharmaceutical preparations, human plasma and the study of the pharmacokinetics of the drug in human body. Nicardipine in plasma were extracted with hexane-butanol (12:1,v/v after addition of borate buffer (0.5 M, pH=9.0, and then measured by HPLC-UV using a Waters Symmetry C18 column as stationary phase and methanol– triethylamine buffer (0.01M pH 4 with acetic acid (70:30 as mobile phase. Nicardipine was quantified by ultraviolet absorbance at 353 nm. The method proved to be linear in the pure drug in the ranges of 15-200 ng/mL (r=0.9989 and 5-40 ?g/mL (r=0.9995, and for the pharmaceutical preparations and plasma for drug concentrations in the range of 5-40 ?g/mL (r =0.9992 and 25-150 ng/mL (r=0.9991, respectively. The lower limit of detection and the lower quantitation limit of NC in plasma were 11.74 and 35.57 ng/mL, respectively. The method is sensitive and reliable for harmacokineticstudies of nicardipine in humans after the oral administration of immediate-release capsules to healthy subjects.

  19. Determination of antazoline hydrochloride in rat plasma and excreta by reversed-phase ion-pair chromatography and its application to pharmacokinetics.

    Science.gov (United States)

    Wang, Rui; Chu, Yanle; Li, Xiaotian; Wan, Baoluo; Yu, Tong; Wang, Linxi; Hao, Lianqi; Guo, Maowen

    2013-12-01

    A reversed-phase ion pair chromatography method with liquid-liquid extraction analytical method was developed and validated for the determination of antazoline hydrochloride in plasma and excreta of rat. The aim of our study was to characterize the preclinical pharmacokinetics and excretion profiles of antazoline hydrochloride in rats after intravenous injection at the dose of 10 mg/kg. Plasma and excreta samples were extracted with ethyl acetate, and phenacetin was used as the internal standard. The result showed that the method is suitable for the quantification of antazoline hydrochloride in plasma and excreta samples. Analysis of accuracy (90.89-112.33%), imprecision (82.5%) showed adequate values. After a single intravenous administration at 10 mg/kg to rats, plasma concentration profile showed a relative fast elimination proceeding with a terminal elimination half-life of 3.53 h. Approximately 61.8 and 14.2% of the administered dose were recovered in urine and bile after 72 and 24 h post-dosing respectively; 5.9% of the administered dose was recovered in feces after 72 h post-dosing. The above results show that the major elimination route is urinary excretion. Copyright © 2013 John Wiley & Sons, Ltd.

  20. Validation of a LC/MS method for the determination of gemfibrozil in human plasma and its application to a pharmacokinetic study

    Science.gov (United States)

    Rower, Joseph E.; Bushman, Lane R.; Hammond, Kyle P.; Kadam, Rajendra S.; Aquilante, Christina L.

    2011-01-01

    Gemfibrozil, a fibric acid hypolipidemic agent, is increasingly being used in clinical drug-drug interaction studies as an inhibitor of drug metabolizing enzymes and drug transporters. The validation of a fast, accurate, and precise LC/MS method is described for the quantitative determination of gemfibrozil in an EDTA-anticoagulated human plasma matrix. Briefly, gemfibrozil was extracted from human plasma by an acetonitrile protein precipitation method. The assay was reproducible with intra-assay precision between 1.6% and 10.7%, and inter-assay precision ranging from 4.4% to 7.8%. The assay also showed good accuracy, with intra-assay concentrations within 85.6% and 108.7% of the expected value, and inter-assay concentrations within 89.4 to 104.0% of the expected value. The linear concentration range was between 0.5 and 50 μg/mL with a lower limit of quantitation of 0.5 μg/mL when 125 μL of plasma were extracted. This LC/MS method yielded a quick, simple, and reliable protocol for determining gemfibrozil concentrations in plasma and is applicable to clinical pharmacokinetic studies. PMID:21077249

  1. Validation of an LC/MS method for the determination of gemfibrozil in human plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Rower, Joseph E; Bushman, Lane R; Hammond, Kyle P; Kadam, Rajendra S; Aquilante, Christina L

    2010-12-01

    Gemfibrozil, a fibric acid hypolipidemic agent, is increasingly being used in clinical drug-drug interaction studies as an inhibitor of drug metabolizing enzymes and drug transporters. The validation of a fast, accurate and precise LC/MS method is described for the quantitative determination of gemfibrozil in an EDTA-anticoagulated human plasma matrix. Briefly, gemfibrozil was extracted from human plasma by an acetonitrile protein precipitation method. The assay was reproducible with intra-assay precision between 1.6 and 10.7%, and inter-assay precision ranging from 4.4 to 7.8%. The assay also showed good accuracy, with intra-assay concentrations within 85.6-108.7% of the expected value, and inter-assay concentrations within 89.4-104.0% of the expected value. The linear concentration range was between 0.5 and 50 µg/mL with a lower limit of quantitation of 0.5 µg/mL when 125 µL of plasma were extracted. This LC/MS method yielded a quick, simple and reliable protocol for determining gemfibrozil concentrations in plasma and is applicable to clinical pharmacokinetic studies. Copyright © 2010 John Wiley & Sons, Ltd.

  2. Simultaneous determination of sibutramine and its active metabolites in human plasma by LC-MS/MS and its application to a pharmacokinetic study.

    Science.gov (United States)

    Bae, Jung-Woo; Choi, Chang-Ik; Jang, Choon-Gon; Lee, Seok-Yong

    2011-11-01

    A simple and sensitive liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) technique was developed and validated for the determination of sibutramine and its N-desmethyl metabolites (M1 and M2) in human plasma. After extraction with methyl t-butyl ether, chromatographic separation of analytes in human plasma was performed using a reverse-phase Luna C18 column with a mobile phase of acetonitrile-10 mm ammonium formate buffer (50:50, v/v) and quantified by ESI-MS/MS detection in positive ion mode. The flow rate of the mobile phase was 200 μL/min and the retention times of sibutramine, M1, M2 and internal standard (chlorpheniramine) were 1.5, 1.4, 1.3 and 0.9 min, respectively. The calibration curves were linear over the range 0.05-20 ng/mL, for sibutramine, M1 and M2. The lower limit of quantification was 0.05 ng/mL using 500 μL of human plasma. The mean accuracy and the precision in the intra- and inter-day validation for sibutramine, M1 and M2 were acceptable. This LC-MS/MS method showed improved sensitivity and a short run time for the quantification of sibutramine and its two active metabolites in plasma. The validated method was successfully applied to a pharmacokinetic study in human. Copyright © 2011 John Wiley & Sons, Ltd.

  3. Development and validation of an LC–MS/MS method for quantification of NC-8 in rat plasma and its application to pharmacokinetic studies

    Directory of Open Access Journals (Sweden)

    Baxter Hepburn Kachingwe

    2018-01-01

    Full Text Available ent-16-Oxobeyeran-19-N-methylureido (NC-8 is a recently synthesized derivative of isosteviol that showed anti-hepatitis B virus (HBV activity by disturbing replication and gene expression of the HBV and by inhibiting the host toll-like receptor 2/nuclear factor-κB signaling pathway. To study its pharmacokinetics as a part of the drug development process, a highly sensitive, rapid, and reliable liquid chromatography tandem mass spectrometry (LC–MS/MS method was developed and validated for determining NC-8 in rat plasma. After protein precipitation extraction, the chromatographic separation of the analyte and internal standard (IS; diclofenac sodium was performed on a reverse-phase Luna C18 column coupled with a Quattro Ultima triple quadruple mass spectrometer in the multiple-reaction monitoring mode using the transitions, m/z 347.31 → 75.09 for NC-8 and m/z 295.89 → 214.06 for the IS. The lower limit of quantitation was 0.5 ng/mL. The linear scope of the standard curve was between 0.5 and 500 ng/mL. Both the precision (coefficient of variation; % and accuracy (relative error; % were within acceptable criteria of <15%. Recoveries ranged from 104% to 113.4%, and the matrix effects (absolute were non-significant (CV ≤ 6%. The validated method was successfully applied to investigate the pharmacokinetics of NC-8 in male Sprague–Dawley rats. The present methodology provides an analytical means to better understand the preliminary pharmacokinetics of NC-8 for investigations on further drug development.

  4. Quantification of hydroxyurea in human plasma by HPLC-MS/MS and its application to pharmacokinetics in patients with chronic myeloid leukaemia.

    Science.gov (United States)

    Hai, Xin; Guo, Meihua; Gao, Chunlu; Zhou, Jin

    2017-04-15

    Hydroxyurea (HU) has been used in the treatment of chronic myeloid leukaemia (CML) and other myeloproliferative malignancies. Considering patient's wide variation in clinical response to HU, a new and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to monitor patients' compliance to treatment and investigate the pharmacokinetics of HU in patients with CML. Stable isotope labeled HU- 13 C 1 , 15 N 2 was used as internal standard. Plasma samples were treated with acetonitrile to precipitate protein. The supernatant was injected directly without derivatization and separated on a hydrophilic interaction liquid chromatography column. HU was quantitatively analyzed with a mobile phase of acetonitrile-1.5mM ammonium formate (90:10, V:V) within 3min. The proposed method provided a linearity range of 1-200μg/mL. The coefficients of variation for intra- and inter-day precision were less than 2.07% and 4.28%, respectively, while the accuracy (bias) was in the range of -3.77 to 2.96%. This method was satisfactorily applied to the determination of HU in two patients with CML. It is suitable for supporting pharmacokinetic studies and clinical therapeutic monitoring. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Determination of lansoprazole enantiomers in dog plasma by column-switching liquid chromatography with tandem mass spectrometry and its application to a preclinical pharmacokinetic study.

    Science.gov (United States)

    Wang, Hao; Sun, Yantong; Meng, Xiangjun; Yang, Bo; Wang, Jian; Yang, Yan; Gu, Jingkai

    2015-09-01

    Lansoprazole, a selective proton pump inhibitor, has a chiral benzimidazole sulfoxide structure and is used for the treatment of gastric acid hypersecretory related diseases. To investigate its stereoselective pharmacokinetics, a column-switching liquid chromatography with tandem mass spectrometry method was developed for the determination of lansoprazole enantiomers in dog plasma using (+)-pantoprazole as an internal standard. After a simple protein precipitation procedure with acetonitrile, matrix components left behind after sample preparation were further eliminated from the sample by reversed-phase chromatography on a C18 column. The fluent was fed to a chiral column for the separation of lansoprazole enantiomers. Baseline separation of lansoprazole enantiomers was achieved on a Chiralcel OZ-RH column using acetonitrile/0.1% formic acid in water (35:65, v/v) as the mobile phase at 40°C. The linearity of the calibration curves ranged from 3 to 800 ng/mL for each enantiomer. Intra- and inter-day precisions ranged from 2.1 to 7.3% with an accuracy of ±1.7% for (+)-lansoprazole, and from 1.6 to 6.9% with an accuracy of ±3.5% for (-)-lansoprazole, respectively. The validated method was successfully applied for the stereoselective pharmacokinetic study of lansoprazole in beagle dog after intravenous infusion. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Dosimetry methods

    DEFF Research Database (Denmark)

    McLaughlin, W.L.; Miller, A.; Kovacs, A.

    2003-01-01

    Chemical and physical radiation dosimetry methods, used for the measurement of absorbed dose mainly during the practical use of ionizing radiation, are discussed with respect to their characteristics and fields of application....

  7. Modeling and optimization of tissue 10B concentration and dosimetry for arbitrary BPA-F infusion schedules in humans

    International Nuclear Information System (INIS)

    Kiger, W.S. III; Newton, T.H.; Palmer, M.R.

    2000-01-01

    Separate compartmental models have been derived for the concentration of 10 B resulting from BPA-F infusion in the central vascular space (i.e., blood or, more appropriately, plasma) and in glioblastoma multiforme and normal brain. By coupling the model for the temporal variation of 10 B concentration in the central vascular space with that for tissue, the dynamic behavior of the 10 B concentration and the resulting dosimetry in the relevant tissues and blood may be predicted for arbitrary infusion schedules. This coupled model may be used as a tool for identifying the optimal time for BNCT irradiation and optimal BPA-F infusion schedule (i.e., temporal targeting) in humans without the need for expensive and time-consuming pharmacokinetic studies for every infusion schedule considered. This model was used to analyze the concentration profiles resulting from a wide range of infusion schedules and their implications for dosimetry. (author)

  8. Simultaneous Determination of Seven Components in Rat Plasma by the UPLC-MS/MS Method and Application of Pharmacokinetic Studies to SimiaoYong’an Decoction

    Directory of Open Access Journals (Sweden)

    Yuanyan Liu

    2017-11-01

    Full Text Available SimiaoYong’an Decoction (SYD is a classical traditional Chinese prescription that is used for the treatment of gangrene, heat-clearing, detoxification and pain alleviation. We developed a sensitive ultra-performance liquid chromatography-tandem mass spectrum (UPLC-MS/MS method for the simultaneous determination of seven major active ingredients of SYD extract (i.e., harpagide, chlorogenic acid, sweroside, loganin, liquiritin, angoroside C and harpagoside in rat plasma. The preliminary steps in the plasma analysis were the addition of an internal standard such as linarin, followed by protein precipitation with methanol. Separation of the active ingredients was performed on an ACQUITY UPLC® BEH C18 column (100 mm × 2.1 mm, 1.7 μm at a flow rate of 0.2 mL/min with methanol/water 0.1% formic acid aqueous (V/V as the mobile phase. Detection was performed on a triple quadrupole tandem MS (QqQ-MS via negative ion electrospray ionization in multiple reactions monitoring (MRM mode. All calibration curves showed good linearity (r > 0.99 over the concentration range with a low limit of quantification between 0.029 and 5.813 ng/mL. Precision was evaluated by intra-day and inter-day assays, and the percentages of the RSD were all within 8.1%. The extraction efficiency and matrix effect were 80.6–113.6% and 82.9–99.5%, respectively. The validated method was successfully applied to a pharmacokinetic study in rats after oral administration of SYD extract and the corresponding single and combined traditional Chinese medicines (TCMs. The pharmacokinetic properties of the seven ingredients showed dynamic changes due to counteraction among the different coexisting components. The established approach has proven useful in the study of the active constituents in a traditional Chinese prescription.

  9. Simultaneous determination of dextromethorphan, dextrorphan and doxylamine in human plasma by HPLC coupled to electrospray ionization tandem mass spectrometry: application to a pharmacokinetic study.

    Science.gov (United States)

    Donato, J L; Koizumi, F; Pereira, A S; Mendes, G D; De Nucci, G

    2012-06-15

    In the present study, a fast, sensitive and robust method to quantify dextromethorphan, dextrorphan and doxylamine in human plasma using deuterated internal standards (IS) is described. The analytes and the IS were extracted from plasma by a liquid-liquid extraction (LLE) using diethyl-ether/hexane (80/20, v/v). Extracted samples were analyzed by high performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Chromatographic separation was performed by pumping the mobile phase (acetonitrile/water/formic acid (90/9/1, v/v/v) during 4.0min at a flow-rate of 1.5 mL min⁻¹ into a Phenomenex Gemini® C18, 5 μm analytical column (150 × 4.6 mm i.d.). The calibration curve was linear over the range from 0.2 to 200 ng mL⁻¹ for dextromethorphan and doxylamine and 0.05 to 10 ng mL⁻¹ for dextrorphan. The intra-batch precision and accuracy (%CV) of the method ranged from 2.5 to 9.5%, and 88.9 to 105.1%, respectively. Method inter-batch precision (%CV) and accuracy ranged from 6.7 to 10.3%, and 92.2 to 107.1%, respectively. The run-time was for 4 min. The analytical procedure herein described was used to assess the pharmacokinetics of dextromethorphan, dextrorphan and doxylamine in healthy volunteers after a single oral dose of a formulation containing 30 mg of dextromethorphan hydrobromide and 12.5mg of doxylamine succinate. The method has high sensitivity, specificity and allows high throughput analysis required for a pharmacokinetic study. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Development and validation of bioanalytical UHPLC-UV method for simultaneous analysis of unchanged fenofibrate and its metabolite fenofibric acid in rat plasma: Application to pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Rayan G. Alamri

    2017-01-01

    Full Text Available A simple, precise, selective and fast ultra-high performance liquid chromatography (UHPLC-UV method has been developed and validated for the simultaneous determination of a lipid regulating agent fenofibrate and its metabolite fenofibric acid in rat plasma. The chromatographic separation was carried out on a reversed-phase Acquity® BEH C18 column using methanol–water (65:35, v/v as the mobile phase. The isocratic flow was 0.3 ml/min with rapid run time of 2.5 min and UV detection was at 284 nm. The method was validated over a concentration range of 100–10000 ng/ml (r2 ⩾ 0.9993. The selectivity, specificity, recovery, accuracy and precision were validated for determination of fenofibrate/fenofibric acid in rat plasma. The lower limits of detection and quantitation of the method were 30 and 90 ng/ml for fenofibrate and 40 and 100 ng/ml for fenofibric acid, respectively. The within and between-day coefficients of variation were less than 5%. The validated method has been successfully applied to measure the plasma concentrations in pharmacokinetics study of fenofibrate in an animal model to illustrate the scope and application of the method.

  11. Simple protein precipitation extraction technique followed by validated chromatographic method for linezolid analysis in real human plasma samples to study its pharmacokinetics.

    Science.gov (United States)

    Mohammed, Samah A; Eissa, Maya S; Ahmed, Hytham M

    2017-02-01

    Fast and sensitive HPLC method was developed, optimized and validated for quantification of linezolid (LNZ) in human plasma using guaifenesin as an internal standard (IS). Analyte and IS were extracted from plasma by simple protein precipitation extraction technique using methanol as the precipitating solvent. The pretreated samples were injected in a mobile phase formed of acetonitrile:water:methanol (20:70:10v/v/v) in an isocratic mode at a flow rate of 1.5mL/min with UV detection at 251nm. Separation was done using Aglient ODS C 18 . The method showed linearity in the range of 0.75-50μg/mL with correlation coefficients equals to 0.9991. Precision and accuracy were in conformity with the criteria normally accepted in bio-analytical method validation. The RSDs for intra- and inter-day assays were <3.56 and 4.63%, respectively. The intra- and inter-day accuracies were 94.67-98.28% and 91.25-96.18%, respectively. The mean absolute recoveries ranged from 92.56±1.78 to 95.24±2.84. According to stability results, LNZ was stable in human plasma during the storage and analysis. LNZ a pharmacokinetic behavior was studied by applying the proposed analytical method. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Fast and parallel determination of PCB 77 and PCB 180 in plasma using ultra performance liquid chromatography with diode array detection: A pharmacokinetic study in Swiss albino mouse.

    Science.gov (United States)

    Ramanujam, N; Sivaselvakumar, M; Ramalingam, S

    2017-11-01

    A simple, sensitive and reproducible ultra-performance liquid chromatography (UPLC) method has been developed and validated for simultaneous estimation of polychlorinated biphenyl (PCB) 77 and PCB 180 in mouse plasma. The sample preparation was performed by simple liquid-liquid extraction technique. The analytes were chromatographed on a Waters Acquity H class UPLC system using isocratic mobile phase conditions at a flow rate of 0.3 mL/min and Acquity UPLC BEH shield RP 18 column maintained at 35°C. Quantification was performed on a photodiode array detector set at 215 nm and PCB 101 was used as internal standard (IS). PCB 77, PCB 180, and IS retention times were 2.6, 4.7 and 2.8 min, respectively, and the total run time was 6 min. The method was validated for specificity, selectivity, recovery, linearity, accuracy, precision and sample stability. The calibration curve was linear over the concentration range 10-3000 ng/mL for PCB 77 and PCB 180. Intra- and inter-day precisions for PCBs 77 and 180 were found to be good with CV <4.64%, and the accuracy ranged from 98.90 to 102.33% in mouse plasma. The validated UPLC method was successfully applied to the pharmacokinetic study of PCBs 77 and 180 in mouse plasma. Copyright © 2017 John Wiley & Sons, Ltd.

  13. A novel HPLC-MS/MS method for the simultaneous determination of astemizole and its major metabolite in dog or monkey plasma and application to pharmacokinetics.

    Science.gov (United States)

    Back, Hyun-moon; Lee, Jong-Hwa; Chae, Jung-woo; Song, Byungjeong; Seo, Joung-Wook; Yun, Hwi-yeol; Kwon, Kwang-il

    2015-10-10

    Astemizole (AST), a second-generation antihistamine, is metabolized to desmethyl astemizole (DEA), and although it has been removed from the market for inducing QT interval prolongation, it has reemerged as a potential anticancer and antimalarial agent. This report describes a novel high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneously determining the concentrations of AST and DEA in beagle dog and cynomolgus monkey plasma with simple preparation method and short retention time. Prior to HPLC analyses, the plasma samples were extracted with simple liquid-liquid extraction method. The isocratic mobile phase was 0.025% trifluoroacetic acid (TFA dissolved in acetonitrile) and 20 mM ammonium acetate (94:6) at a flow rate of 0.25 mL/min and diphenhydramine used as internal standard. In MS/MS analyses, precursor ions of the analytes were optimized as protonated molecular ions: [M+H](+). The lower limit of quantification of astemizole was 2.5 ng/mL in both species and desmethyl astemizole were 7.5 ng/mL and 10 ng/mL in dog and monkey plasma, respectively. The accuracy, precision, and stability of the method were in accordance with FDA guidelines for the validation of bioanalytical methods. Finally this validated method was successfully applied to a pharmacokinetic study in dogs and monkeys after oral administration of 10 mg/kg AST. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Fast and sensitive HPLC/UV method for cefazolin quantification in plasma and subcutaneous tissue microdialysate of humans and rodents applied to pharmacokinetic studies in obese individuals.

    Science.gov (United States)

    Palma, Eduardo Celia; Laureano, João Victor; de Araújo, Bibiana Verlindo; Meinhardt, Nelson Guardiola; Stein, Airton Tetelbom; Dalla Costa, Teresa

    2018-04-14

    Antimicrobial prophylactic dosing of morbidly obese patients may differ from normal weighted individuals owing to alterations in drug tissue distribution. Drug subcutaneous tissue distribution can be investigated by microdialysis patients and animals. The need for cefazolin prophylactic dose adjustment in obese patients remains under discussion. The paper describes the validation of an HPLC-UV method for cefazolin quantification in plasma and microdialysate samples from clinical and pre-clinical studies. A C 18 column with an isocratic mobile phase was used for drug separation, with detection at 272 nm. Total and unbound cefazolin lower limit of quantitation was 5 μg/mL in human plasma, 2 μg/mL in rat plasma, and 0.5 and 0.025 μg/mL in human and rat microdialysate samples, respectively. The maximum intra- and inter-day imprecisions were 10.7 and 8.1%, respectively. The inaccuracy was <9.7%. The limit of quantitation imprecision and inaccuracy were < 15%. Cefazolin stability in the experimental conditions was confirmed. Cefazolin plasma concentrations and subcutaneous tissue penetration were determined by microdialysis in morbidly obese patients (2 g i.v. bolus) and diet-induced obese rats (30 mg/kg i.v. bolus) using the method. This method has the main advantages of easy plasma clean-up and practicability and has proven to be useful in cefazolin clinical and pre-clinical pharmacokinetic investigations. Copyright © 2018 John Wiley & Sons, Ltd.

  15. Internal Dosimetry. Chapter 18

    Energy Technology Data Exchange (ETDEWEB)

    Hindorf, C. [Department of Radiation Physics, Skåne University Hospital, Lund (Sweden)

    2014-12-15

    The Committee on Medical Internal Radiation Dose (MIRD) is a committee within the Society of Nuclear Medicine. The MIRD Committee was formed in 1965 with the mission to standardize internal dosimetry calculations, improve the published emission data for radionuclides and enhance the data on pharmacokinetics for radiopharmaceuticals [18.1]. A unified approach to internal dosimetry was published by the MIRD Committee in 1968, MIRD Pamphlet No. 1 [18.2], which was updated several times thereafter. Currently, the most well known version is the MIRD Primer from 1991 [18.3]. The latest publication on the formalism was published in 2009 in MIRD Pamphlet No. 21 [18.4], which provides a notation meant to bridge the differences in the formalism used by the MIRD Committee and the International Commission on Radiological Protection (ICRP) [18.5]. The formalism presented in MIRD Pamphlet No. 21 [18.4] will be used here, although some references to the quantities and parameters used in the MIRD primer [18.3] will be made. All symbols, quantities and units are presented.

  16. Identification of intestinal loss of a drug through physiologically based pharmacokinetic simulation of plasma concentration-time profiles.

    Science.gov (United States)

    Peters, Sheila Annie

    2008-01-01

    Despite recent advances in understanding of the role of the gut as a metabolizing organ, recognition of gut wall metabolism and/or other factors contributing to intestinal loss of a compound has been a challenging task due to the lack of well characterized methods to distinguish it from first-pass hepatic extraction. The implications of identifying intestinal loss of a compound in drug discovery and development can be enormous. Physiologically based pharmacokinetic (PBPK) simulations of pharmacokinetic profiles provide a simple, reliable and cost-effective way to understand the mechanisms underlying pharmacokinetic processes. The purpose of this article is to demonstrate the application of PBPK simulations in bringing to light intestinal loss of orally administered drugs, using two example compounds: verapamil and an in-house compound that is no longer in development (referred to as compound A in this article). A generic PBPK model, built in-house using MATLAB software and incorporating absorption, metabolism, distribution, biliary and renal elimination models, was employed for simulation of concentration-time profiles. Modulation of intrinsic hepatic clearance and tissue distribution parameters in the generic PBPK model was done to achieve a good fit to the observed intravenous pharmacokinetic profiles of the compounds studied. These optimized clearance and distribution parameters are expected to be invariant across different routes of administration, as long as the kinetics are linear, and were therefore employed to simulate the oral profiles of the compounds. For compounds with reasonably good solubility and permeability, an area under the concentration-time curve for the simulated oral profile that far exceeded the observed would indicate some kind of loss in the intestine. PBPK simulations applied to compound A showed substantial loss of the compound in the gastrointestinal tract in humans but not in rats. This accounted for the lower bioavailability of the

  17. Clinical dosimetry

    International Nuclear Information System (INIS)

    Rassow, J.

    1973-01-01

    The main point of this paper on clinical dosimetry which is to be understood here as application of physical dosimetry on accelerators in medical practice, is based on dosimetric methodics. Following an explanation of the dose parameters and description of the dose distribution important for clinical practice as well as geometric irradiation parameters, the significance of a series of physical parameters such as accelerator energy, surface energy of average stopping power etc. is dealt with in detail. Following a section on field homogenization with bremsstrahlung and electron radiation, details on dosimetry in clinical practice are given. Finally, a few problems of dosemeter or monitor calibration on accelerators are described. The explanations are supplemented by a series of diagrams and tables. (ORU/LH) [de

  18. Simultaneous Determination and Pharmacokinetic Study of Quercetin, Luteolin, and Apigenin in Rat Plasma after Oral Administration of Matricaria chamomilla L. Extract by HPLC-UV

    Directory of Open Access Journals (Sweden)

    Xiaoxv Dong

    2017-01-01

    Full Text Available A simple and sensitive HPLC-UV method has been developed for the simultaneous determination of quercetin, luteolin, and apigenin in rat plasma after oral administration of Matricaria chamomilla L. extract. The flow rate was set at 1.0 ml/min and the detection wavelength was kept at 350 nm. The calibration curves were linear in the range of 0.11–11.36 μg/ml for quercetin, 0.11–11.20 μg/ml for luteolin, and 0.11–10.60 μg/ml for apigenin, respectively. The intraday and interday precisions (RSD were less than 8.32 and 8.81%, respectively. The lower limits of quantification (LLOQ of the three compounds were 0.11 μg/ml. The mean recoveries for quercetin, luteolin, and apigenin were 99.11, 95.62, and 95.21%, respectively. Stability studies demonstrated that the three compounds were stable in the preparation and analytical process. The maximum plasma concentration (Cmax was 0.29 ± 0.06, 3.04 ± 0.60, and 0.42 ± 0.10 μg/ml, respectively. The time to reach the maximum plasma concentration (Tmax was 0.79 ± 0.25, 0.42 ± 0.09, and 0.51 ± 0.13 h, respectively. The validated method was successfully applied to investigate the pharmacokinetics study of quercetin, luteolin, and apigenin in rat plasma after oral administration of M. chamomilla extract.

  19. Validated HPLC method for the quantitative determination of CoQ(10) in dog plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Yuan, Bo; Liu, Chunling; Xu, Pingwei; Lin, Lin; Pan, Cheng; Wang, Linglan; Xu, Haiyan

    2011-09-01

    Coenzyme Q(10) (CoQ(10) ) is a naturally occurring compound located in all membranes throughout the cell. A rapid and sensitive HPLC method was developed to determine the concentration of CoQ(10) in dog plasma using a surrogate matrix. Chromatographic separation was carried out on a Diamonsil C(18) column with the UV detector set at 275 nm. Methanol-2-propanol (40:60, v/v) was used as a mobile phase delivered at a flow rate of 1.0 mL/min. Calibrators were prepared using blank plasma-K(2) HPO(4) buffer (50 mm, pH 8.0)-saline (1:3:6, v/v/v) as surrogate matrix. It was shown that the surrogate matrix had similar properties to dog plasma for CoQ(10) in extraction, freeze-thaw and stability. The assay was linear over the concentration range of 0.10-100 µg/mL. The intra- and inter-day precisions were within 13.3% in terms of relative standard deviation (RSD%) and the accuracy was within ±7.5% in terms of relative error. This simple and reproducible HPLC method with less plasma volume (0.4 mL) and adequate sensitivity was successfully applied to pharmacokinetic studies of CoQ(10) in dogs and an investigation of the effect of CoQ(10) formulation on CoQ(10) baseline levels. Copyright © 2010 John Wiley & Sons, Ltd.

  20. A validated LC-MS/MS method for the determination of senkyunolide I in dog plasma and its application to a pharmacokinetic and bioavailability studies.

    Science.gov (United States)

    Li, Jin-Qi; Wang, Jia-Feng; Li, Jie; Zhang, Shu-Han; He, Dan; Tong, Rong-Sheng; She, Shu-Ya

    2018-05-01

    Senkyunolide I is one of the major bioactive components in the herbal medicine Ligusticum chuanxiong. The aim of this study was to develop and validate a fast, simple and sensitive LC-MS/MS method for the determination of senkyunolide I in dog plasma. The plasma samples were processed with acetonitrile and separated on a Waters Acquity UPLC BEH C 18 column (50 × 2.1 mm, 1.7 μm). The mobile phase consisted of 0.1% formic acid aqueous and acetonitrile was delivered at a flow rate of 0.3 mL min -1 . The detection was achieved in the positive selected reaction monitoring mode with precursor-to-product transitions at m/z 225.1 → 161.1 for senkyunolide I and at m/z 349.1 → 305.1 for an internal standard. The assay was linear over the tested concentration range, from 0.5 ng mL -1 to 1000 ng mL -1 , with a correlation coefficient >0.9992. The mean extraction recovery from dog plasma was within the range of 85.78-93.25%, while the matrix effect of the analyte was within the range of 98.23-108.89%. The intra- and inter-day precisions (RSD) were dogs. The results demonstrated that (a) senkyunolide I showed short elimination half-life (dog, (b) its oral bioavailability was >40% and (c) senkyunolide I showed dose-independent pharmacokinetic profiles in dog plasma over the dose range of 1-50 mg kg -1 . Copyright © 2018 John Wiley & Sons, Ltd.

  1. Simultaneous estimation of lisofylline and pentoxifylline in rat plasma by high performance liquid chromatography-photodiode array detector and its application to pharmacokinetics in rat.

    Science.gov (United States)

    Italiya, Kishan S; Sharma, Saurabh; Kothari, Ishit; Chitkara, Deepak; Mittal, Anupama

    2017-09-01

    Lisofylline (LSF) is an anti-inflammatory and immunomodulatory agent with proven activity in serious infections associated with cancer chemotherapy, hyperoxia-induced acute lung injury, autoimmune disorders including type-1 diabetes (T1DM) and islet rejection after islet transplantation. It is also an active metabolite of another anti-inflammatory agent, Pentoxifylline (PTX). LSF bears immense therapeutic potential in multiple pharmacological activities and hence appropriate and accurate quantification of LSF is very important. Although a number of analytical methods for quantification of LSF and PTX have been reported for pharmacokinetics and metabolic studies, each of these have certain limitations in terms of large sample volume required, complex extraction procedure and/or use of highly sophisticated instruments like LC-MS/MS. The aim of current study is to develop a simple reversed-phase HPLC method in rat plasma for simultaneous determination of LSF and PTX with the major objective of ensuring minimum sample volume, ease of extraction, economy of analysis, selectivity and avoiding use of instruments like LC-MS/MS to ensure a widespread application of the method. A simple liquid-liquid extraction method using methylene chloride as extracting solvent was used for extracting LSF and PTX from rat plasma (200μL). Samples were then evaporated, reconstituted with mobile phase and injected into HPLC coupled with photo-diode detector (PDA). LSF, PTX and 3-isobutyl 1-methyl xanthine (IBMX, internal standard) were separated on Inertsil® ODS (C18) column (250×4.6mm, 5μm) with mobile phase consisting of A-methanol B-water (50:50v/v) run in isocratic mode at flow rate of 1mL/min for 15min and detection at 273nm. The method showed linearity in the concentration range of 50-5000ng/mL with LOD of 10ng/mL and LLOQ of 50ng/mL for both LSF and PTX. Weighted linear regression analysis was also performed on the calibration data. The mean absolute recoveries were found to be 80

  2. An LC-MS/MS method for simultaneous determination of three Polygala saponin hydrolysates in rat plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Wang, Qian; Xiao, Bing-Xin; Pan, Rui-Le; Liu, Xin-Min; Liao, Yong-Hong; Feng, Li; Cao, Fang-Rui; Chang, Qi

    2015-07-01

    Radix Polygala has a long history of use as a sedative in traditional Chinese medicine and its major ingredients are saponins, which are recognized effective in memory improvement but highly toxic to gastricintestinal mucosa. Polygala saponin hydrolysates (PSH), an alkaline hydrolysis product and also the intestinal metabolites of the saponins, exhibited stronger effects in improving memory of mice and had less toxicity than its original saponins. The present study aims to develop a sensitive LC-MS/MS method for simultaneously determining PSH three major active components, 3,4,5-trimethoxycinnamylic acid (TMCA), p-methoxycinnamylic acid (PMCA) and tenuifolin (TF), in rat plasma and apply the method to a pharmacokinetic study. The acidic plasma (100μl) was treated by liquid-liquid extraction with ethyl acetate and reconstituted sample was analyzed on a C18 column eluted with acetonitrile-water (50:50) containing 0.2% formic acid at 0.4ml/min. The mass detection in negative electrospray ionization was used. The ion pairs for multiple reaction monitoring were set at m/z 237.0/103.0, 177.0/116.6 and 679.5/425.3 for TMCA, PMCA and TF, respectively. Their pharmacokinetic profiles were studied in rats after intravenous and oral dose of PSH at 20 and 100mg/kg, respectively. The calibration curves had good linearity (r(2)>0.99) for TMCA, PMCA and TF within the tested concentration ranges. The limits of detection and quantification were 1, 10, 0.5ng/ml and 10.0, 20.0, 1.0ng/ml, respectively. The intra-day and inter-day precisions were less than 18.9% and accuracies between 93.2% and 113.3%, and the extraction recovery ranged from 91.2% to 112.1% for all analytes. The pharmacokinetic study showed that TMCA, PMCA and TF could be rapidly absorbed into the circulation and reached their peak concentrations at about 9.1, 9.0 and 24.0min, respectively. TF had a lower oral bioavailability (2.0%) than TMCA (90.1%) and PMCA (96.5%), but it remained in the body much longer (t1/2,

  3. Simultaneous determination of tedizolid and linezolid in rat plasma by ultra performance liquid chromatography tandem mass spectrometry and its application to a pharmacokinetic study.

    Science.gov (United States)

    Yu, Hua-chen; Pan, Chen-wei; Xie, Qi-peng; Zheng, Yi; Hu, Yue-zheng; Lin, Yi-mu

    2016-02-01

    A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to determine tedizolid and linezolid in rat plasma simultaneously. Chromatographic separation was carried out on an Acquity UPLC BEH C18 column and mass spectrometric analysis was performed using a XEVO TQD triple quadruple mass spectrometer coupled with an electrospray ionization (ESI) source in the positive ion mode. Multiple reaction monitoring (MRM) mode was used for quantification using target fragment ions m/z 371.4→343.2 for tedizolid, and m/z 338.3→56.1 for linezolid. This assay method has been fully validated in terms of selectivity, linearity, recovery and matrix effect, accuracy, precision and stability. The linearity of this method was found to be within the concentration range of 5-5000ng/mL for tedizolid, and 10-10,000ng/mL for linezolid in rat plasma, respectively. Only 3.0min was needed for an analytical run. This assay was used to support a preclinical study where multiple oral doses were administered to rats to investigate the pharmacokinetics of tedizolid and linezolid. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Simultaneous determination of eight bioactive components of Qishen Yiqi dripping pills in rat plasma using UFLC-MS/MS and its application to a pharmacokinetic study.

    Science.gov (United States)

    Shao, Yaping; Zhang, Wen; Tong, Ling; Huang, Jingyi; Li, Dongxiang; Nie, Wei; Zhu, Yan; Li, Yunfei; Lu, Tao

    2017-08-01

    In this study, a rapid and reliable ultra-fast liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of eight active ingredients, including astragaloside IV, ononin, tanshinol, protocatechualdehyde, protocatechuic acid, salvianolic acid D, rosmarinic acid and ginsenoside Rg 1 , in rat plasma. The plasma samples were pretreated by protein precipitation with acetonitrile. Chromatographic separation was performed on a Waters Acquity UPLC® BEH C 18 column (1.7 μm particles, 2.1 × 100 mm). The mobile phase consisted of 0.1% aqueous formic acid (A)-acetonitrile with 0.1% formic acid (B) at a flow rate of 0.4 mL/min. Quantification was performed on a triple quadruple tandem mass spectrometry with electrospray ionization by multiple reaction monitoring both in the negative and in the positive ion mode. The lower limit of quantification of tanshinol was 2.0 ng/mL and the others were 5.0 ng/mL. The extraction recoveries, matrix effects, intra- and inter-day precision and accuracy of eight tested components were all within acceptable limits. The validated method was successfully applied to the pharmacokinetic study of the eight active constituents after intragastric administration of three doses (1.0, 3.0, 6.0 g/kg body weight) of Qishen Yiqi Dripping Pills to rats. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Simultaneous determination of multicomponent of acetylkitasamycin and kitasamycin by LC-MS/MS in swine plasma and its application in a pharmacokinetic study.

    Science.gov (United States)

    Pan, Yuanhu; Zhang, Heying; Xi, Chenglong; Huang, Lingli; Xie, Shuyu; Chen, Dongmei; Tao, Yanfei; Liu, Zhenli; Yuan, Zonghui

    2018-05-02

    A simple and reliable LC-MS/MS method was established for simultaneous determination of twelve components from acetylkitasamycin and kitasamycin in swine plasma. The analytes were separated by a Shim-pack VP-ODS column with a 25 min gradient elution using 5 mmol/L ammonium acetate and acetonitrile as the mobile phase at a flow rate of 0.2 mL/min. Identification and quantification were accomplished by electrospray ionization (ESI) in positive mode using multiple reaction monitoring (MRM). The LOQ S of acetylkitasamycin A 1 A 3 , A 13 and kitasamycin A 3 , A 13 were 3 μg/L, and that of the other 8 components were 5 μg/L. The mean recoveries of kitasamycin and acetylkitasamycin ranged from 85.3 to 103.5 %. The developed method was successfully applied to a pharmacokinetic study in swine after intravenous (IV) and oral (PO) administration of acetylkitasamycin. The result showed that the plasma concentrations of acetylkitsamycin components were much higher than that of kitasamycin in swine after IV and PO, in which acetylkitsamycin A 4 A 5 was the highest component at each time point. This article is protected by copyright. All rights reserved.

  6. Determination of asperosaponin VI in dog plasma by high-performance liquid chromatography-tandem mass spectrometry and its application to a pilot pharmacokinetic study.

    Science.gov (United States)

    Shakya, Shailendra; Zhu, He; Ding, Li; Du, Xiao Lang; Qi, Xie Min; Yang, Xiao Lin; Yang, Zhong Lin

    2012-01-01

    A sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the determination of asperosaponin VI in beagle dog plasma using glycyrrhizic acid as the internal standard (IS). Plasma samples were simply pretreated with methanol for deproteinization. Chromatographic separation was performed on a Hedera ODS-2 column using mobile phase of methanol-10 mm ammonium acetate buffer solution containing 0.05% acetic acid (71:29, v/v) at a flow rate of 0.38 mL/min. Asperosaponin VI and the IS were eluted at 2.8 and 1.9 min, respectively, ionized in negative ion mode, and then detected by multiple reaction monitoring. The detection used the transitions of the deprotonated molecules at m/z 927.5 → 603.4 for asperosaponin VI and m/z 821.4 → 645.4 for glycyrrhizic acid (IS). The assay was linear over the concentration range of 0.15-700 ng/mL and was successfully applied to a pilot pharmacokinetic study in beagle dogs. Copyright © 2011 John Wiley & Sons, Ltd.

  7. Simultaneous quantification of five steroid saponins from Dioscorea zingiberensis C.H.Wright in rat plasma by HPLC-MS/MS and its application to the pharmacokinetic studies

    Science.gov (United States)

    Zhang, Xinxin; Li, Jing; Ito, Yoichiro; Sun, Wenji

    2014-01-01

    A simple, reliable and sensitive high-performance liquid chromatography tandem mass spectrometry method (HPLC-MS/MS) was established for simultaneous analyses of the following 5 steroid saponins in rat plasma after the single dose administration of total steroid saponins extracted from the rhizome of Dioscorea zingiberensis C.H.Wright for the first time. Protodioscin, huangjiangsu A, zingiberensis new saponin, dioscin, and gracillin were quantified using ginsenoside Rb1 as the internal standard (IS). The plasma samples were pretreated by a single step acetonitrile-mediated protein precipitation. The chromatographic separation was performed on an Inersil ODS-3 C18 column (250 mm × 4.6 mm, 5 μm) with the mobile phase composed of acetonitrile and water containing 0.1% formic acid under a gradient elution mode at 0.2 mL min−1 using a microsplit after the eluent from the HPLC apparatus. The quantification was accomplished on a triple quadrupole tandem mass spectrometer using the multiple reaction monitoring (MRM) in the positive ionization mode. The above five analytes were stable under sample storage and preparation conditions applied in the present study. The linearity, precision, accuracy, and recoveries of the analysis confirmed the requirements for quality-control purposes. After validation, this proposed method was successfully adopted to investigate the pharmacokinetic parameters of these five analytes. PMID:25201262

  8. Simultaneous quantitation of lamivudine, zidovudine and nevirapine in human plasma by liquid chromatography–tandem mass spectrometry and application to a pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Murali Krishna Matta

    2012-10-01

    Full Text Available A rapid and sensitive LC–MS/MS method for the simultaneous quantitation of lamivudine, zidovudine and nevirapine in human plasma using abacavir as internal standard has been developed and validated. The analytes and IS were extracted from plasma by solid phase extraction using Oasis HLB cartridges and separated on a Hypurity Advance C18 column using a mixture of acetonitrile:0.1% formic acid (76:24, v/v at a flow rate of 0.8 mL/min. Detection involved an API-4000 LC–MS/MS with electrospray ionization in the positive ion mode and multiple-reaction monitoring for analysis. The method was validated according to FDA guidelines and shown to provide intra- and inter-day precision and accuracy within acceptable limits in a run time of only 3.5 min. The method was successfully applied to a pharmacokinetic study involving a single oral administration of a combination tablet to human male volunteers.

  9. Development of an LC–MS/MS method for the quantitation of deoxyglycychloxazol in rat plasma and its application in pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Rongshan Li

    2016-06-01

    Full Text Available Deoxyglycychloxazol (TY501 is a glycyrrhetinic acid derivative which exhibits high anti-inflammatory activity and reduced pseudoaldosteronism compared to glycyrrhetinic acid. In this study, a sensitive and rapid liquid chromatography–tandem mass spectrometry (LC–MS/MS method was established for the quantitation of TY501 in rat plasma. Plasma samples were treated by precipitating protein with methanol and supernatants were separated by a Symmetry C8 column with the mobile phase consisting of methanol and 10 mM ammonium formate (containing 0.1% of formic acid (90:10, v/v. The selected reaction monitoring (SRM transitions were performed at m/z 647.4→191.2 for TY501 and m/z 473.3→143.3 for astragaloside aglycone (IS in the positive ion mode with atmospheric pressure chemical ionization (APCI source. Calibration curve was linear over the concentration range of 5–5000 ng/mL. The lower limit of quantification was 5 ng/mL. The mean recovery was over 88%. The intra- and inter-day precisions were lower than 6.0% and 12.8%, respectively, and the accuracy was within ±1.3%. TY501 was stable under usual storage conditions and handling procedure. The validated method has been successfully applied to a pharmacokinetic study after oral administration of TY501 to rats at a dosage of 10 mg/kg.

  10. Simultaneous Determination and Pharmacokinetic Study of Six Components in Rat Plasma by HPLC-MS/MS after Oral Administration of Acanthopanax sessiliflorus Fruit Extract

    Directory of Open Access Journals (Sweden)

    Peng Du

    2016-12-01

    Full Text Available A specific and reliable HPLC-MS/MS method was developed and validated for the simultaneous determination of protocatechuic acid (PCA, scopolin, (−-pinoresinol-4,4′-di-O-β-d-glucopyranoside (PDG, acanthoside D, acanthoside B and hyperin in rat plasma for the first time. The analytes were separated on a C18 column (50 × 2.1 mm, 1.8 µm and a triple-quadrupole mass spectrometer equipped with an electrospray ionization (ESI source was used for detection. The rat plasma sample was prepared using the protein precipitation procedure. The calibration curves were linear over a concentration range of 1.2–1200.0 ng/mL for PCA, 0.96–960.0 ng/mL for scopolin, 1.12–1120.0 ng/mL for PDG, 1.32–1320.0 ng/mL for acanthoside D, 0.99–990.0 ng/mL for acanthoside B and 1.01–1010.0 ng/mL for hyperin. The intra-day and inter-day precision was less than 11.4% and the relative error (RE was all within ±15%. The validated method was successfully applied to assess the pharmacokinetics characteristics after the extracts of Acanthopanax sessiliflorus fruits were orally administered to the Sprague-Dawley rat.

  11. Quantification of triacontanol and its PEGylated prodrug in rat plasma by GC-MS/MS: Application to a pre-clinical pharmacokinetic study.

    Science.gov (United States)

    Lu, Xiaoyu; Fang, Min; Dai, Yu; Yang, Yue; Fan, Ali; Xu, Jiaqiu; Qin, Zhiying; Lu, Yang; Zhao, Di; Chen, Xijing; Li, Ning

    2018-04-24

    PEGylation techniques have been increasingly employed in drug delivery system and chemical modification of compounds with low aqueous solubility. Triacontanol (TA) is a natural product with several pharmacological activities, but its low aqueous solubility significantly limited its application. PEGylated triacontanol (PEG-TA) was designed as the prodrug to improve the aqueous solubility and pharmacokinetic properties of TA. On the basis of salting-out assisted liquid-liquid extraction (SALLE) and saponification sample preparation procedure, a reliable gas chromatography tandem mass spectrometric (GC-MS/MS) method was developed and validated for the quantification of PEG-TA and its metabolite TA in rat plasma after separation and transformation. Acetonitrile-methanol (9:1, v/v) and ammonium acetate (10 M) were utilized to separate PEG-TA and TA (including conjugated TA with fatty acid). Saponification facilitated the complete conversion of PEG-TA into TA, so PEG-TA could be indirectly quantified. The results revealed that the GC-MS/MS method had excellent selectivity, accuracy and linearity. Calibration curves were linear (R 2 >0.99) within the range of 20.0-1000.0 ng/mL for TA and 100.0-10,000.0 ng/mL for PEG-TA. The intra- and inter-day precision of quality control samples were within 15%, and their accuracy values varied from 93.54% to 113.38%. This analytical method has been successfully applied to pharmacokinetic study of PEG-TA. This study can facilitate the further exploration and quantification of PEGylated prodrugs. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. LC-MS/MS methods for the determination of edaravone and/or taurine in rat plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Tang, Dao-quan; Bian, Ting-ting; Zheng, Xiao-xiao; Li, Ying; Wu, Xiao-wen; Li, Yin-jie; Du, Qian; Jiang, Shui-shi

    2014-09-01

    Three liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were respectively developed and validated for the simultaneous or independent determination of taurine and edaravone in rat plasma using 3-methyl-1-p-tolyl-5-pyrazolone and sulfanilic acid as the internal standards (IS). Chromatographic separations were achieved on an Agilent Zorbax SB-Aq (100 × 2.1 mm, 3.5 µm) column. Gradient 0.03% formic acid-methanol, isocratic 0.1% formic acid-methanol (90:10) and 0.02% formic acid-methanol (40:60) were respectively selected as the mobile phase for the simultaneous determination of two analytes, taurine or edaravone alone. The MS acquisition was performed in multiple reaction monitoring mode with a positive and negative electrospray ionization source. The mass transitions monitored were m/z [M + H](+) 175.1 → 133.0 and [M + H](+) 189.2 → 147.0 for edaravone and its IS, m/z [M - H](-) 124.1 → 80.0 and [M - H](-) 172.0 → 80.0 for taurine and its IS, respectively. The validated methods were successfully applied to study the pharmacokinetic interaction of taurine and edaravone in rats after independent intravenous administration and co-administration with a single dose. Our collective results showed that there were no significant alterations on the main pharmacokinetic parameters (area under concentration-time curve, mean residence time, half-life and clearance) of taurine and edaravone, implying that the proposed combination therapy was pharmacologically feasible. Copyright © 2014 John Wiley & Sons, Ltd.

  13. Rapid and Sensitive LC-MS/MS Method for the Determination of Metoprolol in Beagle Dog Plasma with a Simple Protein Precipitation Treatment and Its Pharmacokinetic Applications

    Directory of Open Access Journals (Sweden)

    Aihua Hong

    2012-03-01

    Full Text Available : A rapid LC-MS/MS method with good accuracy and sensitivity was developed and validated for the pharmacokinetics study of metoprolol (MP in beagle dogs. The plasma samples were simply precipitated by methanol and then analyzed by LC-MS/MS. An Ultimate XB-C18 column (150 × 2.1 mm ID, 5 μm was used for separation, with methanol-water containing 0.2% formic acid (65:35, v/v as the mobile phase at a flow rate of 0.2 mL/min. Monitoring ions of MP and internal standard (hydroxypioglitazone were m/z 268.1/115.6 and m/z 373.1/150.2, respectively. The linear range was 3.03–416.35 ng/mL with an average correlation coefficient of 0.9996, and the limit of quantification was 3.03 ng/mL. The intra- and inter-day precision was less than 15%. At low, middle and high concentrations, the recovery, the matrix effect and the accuracy was in the range of 76.06%–95.25%, 93.67%–104.19% and 95.20%–99.96% respectively. The method was applied for the pharmacokinetics study of MP tartrate tablets (50 mg. The AUC0-t, Tmax and Cmax were respectively 919.88 ± 195.67 μg/L·h, 0.96 ± 0.33 h, 349.12 ± 78.04 ng/mL.

  14. Determination of rabeprazole enantiomers in dog plasma by supercritical fluid chromatography tandem mass spectrometry and its application to a pharmacokinetic study.

    Science.gov (United States)

    Su, Chong; Yang, Hong; Meng, Xiangjun; Fawcett, J Paul; Cao, Jianming; Yang, Yan; Gu, Jingkai

    2017-02-01

    Rabeprazole is a novel benzimidazole proton pump inhibitor used for the treatment of gastrointestinal disorders. It is a chiral molecule that gives rise to the possibility of stereoselective pharmacokinetics. To investigate this phenomenon, a rapid and sensitive chiral assay based on supercritical fluid chromatography tandem mass spectrometry was developed and applied to the determination of (R)-rabeprazole and (S)-rabeprazole in dog plasma. Sample preparation involved protein precipitation with acetonitrile after the addition of (R)-lansoprazole as internal standard. Baseline separation of enantiomers in 4.5 min was achieved on an Acquity UPC 2 system using an ACQUITY UPC 2 Trefoil CEL2 column maintained at 60°C and a mobile phase consisting of methanol/CO 2 (30:70, v/v) delivered at 2.5 mL/min. Detection was achieved by multiple reaction monitoring of the transitions at m/z 360.0→242.2 (rabeprazole) and 370.3→252.0 (internal standard) in the positive ion mode. The assay was linear in the range of 1-1000 ng/mL and free of matrix effects. Intra- and interday precisions were less than 10.0% with accuracy in the range of -2.6 to 3.1%. The method was successfully applied to a pharmacokinetic study of rabeprazole enantiomers after administration of a single oral dose of 10 mg racemate to beagle dogs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Environmental dosimetry

    International Nuclear Information System (INIS)

    Gold, R.

    1977-01-01

    For more than 60 years, natural radiation has offered broad opportunities for basic research as evidenced by many fundamental discoveries. Within the last decade, however, dramatic changes have occurred in the motivation and direction of this research. The urgent need for economical energy sources entailing acceptably low levels of environmental impact has compelled the applied aspects of our radiation environment to become overriding considerations. It is within this general framework that state-of-the-art environmental dosimetry techniques are reviewed. Although applied motivation and relevance underscores the current milieu for both reactor and environmental dosimetry, a perhaps even more unifying force is the broad similarity of reactor and environmental radiation fields. In this review, a comparison of these two mixed radiation fields is presented stressing the underlying similarities that exist. On this basis, the evolution of a strong inner bond between dosimetry methods for both reactor and environmental radiation fields is described. The existence of this bond will be illustrated using representative examples of observed spectra. Dosimetry methods of particularly high applicability for both of these fields are described. Special emphasis is placed on techniques of high sensitivity and absolute accuracy which are capable of resolving the components of these mixed radiation fields

  16. Quantitation of Metformin in Human Plasma and Urine by Hydrophilic Interaction Liquid Chromatography and Application to a Pharmacokinetic Study

    DEFF Research Database (Denmark)

    Nielsen, Flemming; Hougaard Christensen, Mette Marie; Brøsen, Kim

    2014-01-01

    : We describe an analytical method for the quantification of the widely used antihyperglycemic agent, metformin, in human plasma and urine. The separation was performed using isocratic hydrophilic interaction liquid chromatography on a Luna hydrophilic interaction liquid chromatography column (125...

  17. Determination and pharmacokinetic properties of arsenic speciation in Xiao-Er-Zhi-Bao-Wan by high-performance liquid chromatography with inductively coupled plasma mass spectrometry.

    Science.gov (United States)

    Han, Xu; Luo, Jiaoyang; Zhou, Wenju; Yang, Shihai; Yang, Meihua

    2016-10-01

    A method of high performance liquid chromatography with a Hamilton PRP-X100 ion-exchange column (250 × 4.1 mm id, 10 μm) coupled to inductively coupled plasma mass spectrometry was employed to generate a full concentration-time profile of arsenic speciation after oral administration. The results exhibited good linearity and revealed that, in the pills, the average arsenic concentration was 10105.4 ± 380.7 mg/kg, and in the water extraction solution, the inorganic As(III) and As(V) concentrations were 220.1 ± 12.6 and 45.5 ± 2.3 mg/kg, respectively. No trace of monomethyl arsenic acid was detected in any of the plasma samples. We then successfully applied the established methodology to examine the pharmacokinetics of arsenic speciation. The resulting data revealed that, after oral administration in rats, the plasma concentration of each arsenic species reached C max shortly after initial dosing, and that the distribution and elimination of As(V) was faster than that of As(III) and dimethyl arsenic acid. Additionally, the t 1/2 values of As(V), As(III), and dimethyl arsenic acid were 3.4 ± 1.6, 14.3 ± 4.0, and 19.9 ± 1.6 h, respectively. This study provides references for the determination of arsenic speciation in mineral-containing medicines and could serve as a useful tool in measuring the true toxicity in traditional medicines that contain them. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Simultaneous quantification of lenalidomide, ibrutinib and its active metabolite PCI-45227 in rat plasma by LC-MS/MS: application to a pharmacokinetic study.

    Science.gov (United States)

    Veeraraghavan, Sridhar; Viswanadha, Srikant; Thappali, Satheeshmanikandan; Govindarajulu, Babu; Vakkalanka, Swaroopkumar; Rangasamy, Manivannan

    2015-03-25

    Efficacy assessments using a combination of ibrutinib and lenalidomide necessitate the development of an analytical method for determination of both drugs in plasma with precision. A high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of lenalidomide, ibrutinib, and its active metabolite PCI45227 in rat plasma. Extraction of lenalidomide, ibrutinib, PCI45227 and tolbutamide (internal standard; IS) from 50 μl rat plasma was carried out by liquid-liquid extraction with ethyl acetate:dichloromethane (90:10) ratio. Chromatographic separation of analytes was performed on YMC pack ODS AM (150 mm × 4.6 mm, 5 μm) column under gradient conditions with acetonitrile:0.1% formic acid buffer as the mobile phases at a flow rate of 1 ml/min. Precursor ion and product ion transition for analytes and IS were monitored on a triple quadrupole mass spectrometer, operated in the selective reaction monitoring with positive ionization mode. Method was validated over a concentration range of 0.72-183.20 ng/ml for ibrutinib, 0.76-194.33 ng/ml for PCI-45227 and 1.87-479.16 ng/ml for lenalidomide. Mean extraction recovery for ibrutinib, PCI-45227, lenalidomide and IS of 75.2%, 84.5%, 97.3% and 92.3% were consistent across low, medium, and high QC levels. Precision and accuracy at low, medium and high quality control levels were less than 15% across analytes. Bench top, wet, freeze-thaw and long term stability was evaluated for all the analytes. The analytical method was applied to support a pharmacokinetic study of simultaneous estimation of lenalidomide, ibrutinib, and its active metabolite PCI-45227 in Wistar rat. Assay reproducibility was demonstrated by re-analysis of 18 incurred samples. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. A validated HPLC-MS/MS assay for quantifying unstable pharmacologically active metabolites of clopidogrel in human plasma: application to a clinical pharmacokinetic study.

    Science.gov (United States)

    Furlong, Michael T; Savant, Ishani; Yuan, Moucun; Scott, Laura; Mylott, William; Mariannino, Thomas; Kadiyala, Pathanjali; Roongta, Vikram; Arnold, Mark E

    2013-05-01

    Clopidogrel is prescribed for the treatment of Acute Coronary Syndrome and recent myocardial infarction, recent stroke, or established peripheral arterial disease. A sensitive and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay was developed and validated to enable reliable quantification of four diastereomeric and chemically reactive thiol metabolites, two of which are pharmacologically active, in human plasma. The metabolites were stabilized by alkylation of their reactive thiol moieties with 2-bromo-3'-methoxyacetophenone (MPB). Following organic solvent mediated-protein precipitation in a 96-well plate format, chromatographic separation was achieved by gradient elution on an Ascentis Express RP-amide column. Chromatographic conditions were optimized to ensure separation of the four derivatized active metabolites. Derivatized metabolites and stable isotope-labeled internal standards were detected by positive ion electrospray tandem mass spectrometry. The HPLC-MS/MS assay was validated over concentration ranges of 0.125-125 ng/mL for metabolites H1-H3 and 0.101-101 ng/mL for H4. Intra- and inter-assay precision values for replicate quality control samples were within 14.3% for all analytes during the assay validation. Mean quality control accuracy values were within ±6.3% of nominal values for all analytes. Assay recoveries were high (>79%). The four derivatized analytes were stable in human blood for at least 2 h at room temperature and on ice. The analytes were also stable in human plasma for at least 25 h at room temperature, 372 days at -20 °C and -70 °C, and following at least five freeze-thaw cycles. The validated assay was successfully applied to the quantification of all four thiol metabolites in human plasma in support of a human pharmacokinetic study. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. A novel UPLC-MS/MS method for sensitive quantitation of boldine in plasma, a potential anti-inflammatory agent: application to a pharmacokinetic study in rats.

    Science.gov (United States)

    Zeng, Rong-Jie; Li, Yu; Chen, Jian-Zhong; Chou, Gui-Xin; Gao, Yu; Shao, Jing-Wei; Jia, Lee; Wu, Sheng-Dong; Wu, Shui-Sheng

    2015-03-01

    Boldine is a potential anti-inflammatory agent found in several different plants. Published bioanalytical methods using HPLC with ultraviolet and fluorescent detection lacked enough sensitivity and required tedious sample preparation procedures. Herein, we describe the development of a novel ultra-high performance LC with MS/MS for determination of boldine in plasma. Boldine in plasma was recovered by liquid-liquid extraction using 1 mL of methyl tert-butyl ether. Chromatographic separation was performed on a C18 column at 45°C, with a gradient elution consisting of acetonitrile and water containing 0.1% (v/v) formic acid at a flow rate of 0.3 mL/min. The detection was performed on an electrospray triple-quadrupole MS/MS by positive ion multiple reaction monitoring mode. Good linearity (r(2) > 0.9926) was achieved in a concentration range of 2.555-2555 ng/mL with a lower limit of quantification of 2.555 ng/mL for boldine. The intra- and inter-day precisions of the assay were 1.2-6.0 and 1.8-7.4% relative standard deviation with an accuracy of -6.0-8.0% relative error. This newly developed method was successfully applied to a single low-dose pharmacokinetic study in rats and was demonstrated to be simpler and more sensitive than the published methods, allowing boldine quantification in reduced plasma volume. Copyright © 2014 John Wiley & Sons, Ltd.

  1. Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother–infant pairs

    Science.gov (United States)

    Waitt, Catriona; Olagunju, Adeniyi; Nakalema, Shadia; Kyohaire, Isabella; Owen, Andrew; Lamorde, Mohammed; Khoo, Saye

    2018-01-01

    Abstract Background Breast milk transfer of first-line ART from mother to infant is not fully understood. Objectives To determine the concentrations of lamivudine, emtricitabine and tenofovir in maternal blood, breast milk and infant blood from breastfeeding mother–infant pairs. Methods Intensive pharmacokinetic sampling of maternal dried blood spots (DBS), dried breast milk spots (DBMS) and infant DBS from 30 Ugandan and 29 Nigerian mothers receiving first-line ART and their infants was conducted. DBS and DBMS were collected pre-dose and at 5–6 timepoints up to 12 h following observed dosing. Infant DBS were sampled twice during this period. Lamivudine, emtricitabine and tenofovir were quantified using LC-MS/MS, with non-compartmental analysis to calculate key pharmacokinetic parameters. Results Peak concentrations in breast milk from women taking lamivudine and emtricitabine occurred later than in plasma (4–8 h compared with 2 h for lamivudine and 2–4 h for emtricitabine). Consequently, the milk-to-plasma (M:P) ratio of lamivudine taken once daily was 0.95 (0.82–1.15) for AUC0–12, whereas for AUC12–20 this was 3.04 (2.87–4.16). Lamivudine was detectable in 36% (14/39) of infants [median 17.7 (16.3–22.7) ng/mL]. For 200 mg of emtricitabine once daily, the median M:P ratio was 3.01 (2.06–3.38). Three infants (19%) had measurable emtricitabine [median 18.5 (17.6–20.8) ng/mL]. For 300 mg of tenofovir once daily, the median M:P ratio was 0.015 (0–0.03) and no infant had measurable tenofovir concentrations. Conclusions Emtricitabine and lamivudine accumulate in breast milk and were detected in breastfeeding infants. In contrast, tenofovir penetrates the breast milk to a small degree, but is undetectable in breastfeeding infants. PMID:29309634

  2. Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother-infant pairs.

    Science.gov (United States)

    Waitt, Catriona; Olagunju, Adeniyi; Nakalema, Shadia; Kyohaire, Isabella; Owen, Andrew; Lamorde, Mohammed; Khoo, Saye

    2018-04-01

    Breast milk transfer of first-line ART from mother to infant is not fully understood. To determine the concentrations of lamivudine, emtricitabine and tenofovir in maternal blood, breast milk and infant blood from breastfeeding mother-infant pairs. Intensive pharmacokinetic sampling of maternal dried blood spots (DBS), dried breast milk spots (DBMS) and infant DBS from 30 Ugandan and 29 Nigerian mothers receiving first-line ART and their infants was conducted. DBS and DBMS were collected pre-dose and at 5-6 timepoints up to 12 h following observed dosing. Infant DBS were sampled twice during this period. Lamivudine, emtricitabine and tenofovir were quantified using LC-MS/MS, with non-compartmental analysis to calculate key pharmacokinetic parameters. Peak concentrations in breast milk from women taking lamivudine and emtricitabine occurred later than in plasma (4-8 h compared with 2 h for lamivudine and 2-4 h for emtricitabine). Consequently, the milk-to-plasma (M:P) ratio of lamivudine taken once daily was 0.95 (0.82-1.15) for AUC0-12, whereas for AUC12-20 this was 3.04 (2.87-4.16). Lamivudine was detectable in 36% (14/39) of infants [median 17.7 (16.3-22.7) ng/mL]. For 200 mg of emtricitabine once daily, the median M:P ratio was 3.01 (2.06-3.38). Three infants (19%) had measurable emtricitabine [median 18.5 (17.6-20.8) ng/mL]. For 300 mg of tenofovir once daily, the median M:P ratio was 0.015 (0-0.03) and no infant had measurable tenofovir concentrations. Emtricitabine and lamivudine accumulate in breast milk and were detected in breastfeeding infants. In contrast, tenofovir penetrates the breast milk to a small degree, but is undetectable in breastfeeding infants.

  3. Development and validation of a HPLC-MS/MS method for the determination of phytolaccagenin in rat plasma and application to a pharmacokinetic study.

    Science.gov (United States)

    Wei, Fenghuan; Singh, Ravi Shankar Prasad; Fueth, Matthias; Swarts, Steven; Okunieff, Paul; Derendorf, Hartmut

    2015-03-25

    Radix Phytolaccae (the dried root of Phytolacca acinosa Roxb. or Phytolacca americana L.) is widely used in East Asian countries for the treatment of inflammation-related diseases. The active component of Radix Phtolaccae is Phytolcaccagenin a triterpenoid saponin. Phytolcaccagenin has anti-inflammatory activities that exceed those of Esculentoside A and its derivatives regarding suppression of LPS-induced inflammation, and has a lower toxicity profile with less hemolysis. To date, no information is available about analytical method and pharmacokinetic studies of phytolaccagenin. To explore PK profile of this compound, a HPLC-MS/MS assay of phytolaccagenin in rat plasma was developed and validated. The method was fully validated according to FDA Guidance for industry. The detection was performed by a triple-quadrupole tandem mass spectrometer with multiple reactions monitoring (MRM) in positive ion mode via electrospray ionization. The monitored transitions were m/z 533.2>515.3 for Phytolcaccagenin, and 491.2>473.2 for I.S. The analysis was performed on a Symmetry C18 column (4.6 mm × 50 mm, 3.5 μm) using gradient elution with the mobile phase consisting of acetonitrile and 0.1% formic acid water at a flow rate of 1 ml/min with a 1:1 splitter ratio. The method was validated with a LLOQ of 20 ng/ml and an ULOQ of 1000 ng/ml. The response versus concentration data were fitted with 1/x weighting and the correlation coefficient (r) were greater than 0.999. The average matrix effect and the average extraction recovery were acceptable. This validation in rat plasma demonstrated that phytolaccagenin was stable for 30 days when stored below -20°C, for 6h at room temperature (RT, 22°C), for 12 h at RT for prepared control samples in auto-sampler vials, and during three successive freeze/thaw cycles results at -20°C. The validated method has been successfully applied to an intravenous bolus pharmacokinetic study of phytolaccagenin in male Sprague-Dawley rats (10 mg

  4. A validated LC–MS/MS method for the determination of tolterodine and its metabolite in rat plasma and application to pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Rihana Parveen Shaik

    2013-12-01

    Full Text Available Liquid chromatography–tandem mass spectrometry (LC–MS/MS method was used for simultaneous quantification of tolterodine and its metabolite 5-hydroxy methyl tolterodine in rat plasma. Tolterodine-d6 and 5-hydroxy methyl tolterodine-d14 were used as internal standards (IS. Chromatographic separation was performed on Ascentis Express RP amide (50 mm×4.6 mm, 2.7 μm column with an isocratic mobile phase composed of 10 mM ammonium acetate and acetonitrile in the ratio of 20:80 (v/v, at a flow-rate of 0.5 mL/min. Tolterodine, tolterodine-d6, 5-hydroxy methyl tolterodine and 5-hydroxy methyl tolterodine-d14 were detected with proton adducts at m/z 326.1→147.1, 332.3→153.1, 342.2→223.1 and 356.2→223.1 in multiple reaction monitoring (MRM positive mode respectively. The drug, metabolite and internal standards were extracted by liquid–liquid extraction method. The method was validated over a linear concentration range of 20.00–5000.00 pg/mL for tolterodine and 20.00–5000.00 pg/mL for 5-hydroxy methyl tolterodine. This method demonstrated intra- and inter-day precision of 0.62–6.36% and 1.73–4.84% for tolterodine, 1.38–4.22% and 1.62–4.25% for 5-hydroxy methyl tolterodine respectively. This method also demonstrated intra- and inter-day accuracy of 98.75–103.56% and 99.20–104.40% for tolterodine, 98.08–104.67% and 98.73–103.06% for 5-hydroxy methyl tolterodine respectively. Both analytes were found to be stable throughout freeze–thaw cycles, bench top and postoperative stability studies. This method was successfully applied for the pharmacokinetic analysis of rat plasma samples following i.v. administration. Keywords: LC–MS/MS, Tolterodine, 5-Hydroxy methyl tolterodine, Pharmacokinetics

  5. Neutron personnel dosimetry

    International Nuclear Information System (INIS)

    Griffith, R.V.

    1981-01-01

    The current state-of-the-art in neutron personnel dosimetry is reviewed. Topics covered include dosimetry needs and alternatives, current dosimetry approaches, personnel monitoring devices, calibration strategies, and future developments

  6. A rapid and sensitive LC-MS/MS method for the determination of Pulsatilla saponin D in rat plasma and its application in a rat pharmacokinetic and bioavailability study.

    Science.gov (United States)

    Ouyang, Hui; Guo, Yicheng; He, Mingzhen; Zhang, Jinlian; Huang, Xiaofang; Zhou, Xin; Jiang, Hongliang; Feng, Yulin; Yang, Shilin

    2015-03-01

    A simple, sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of Pulsatilla saponin D, a potential antitumor constituent isolated from Pulsatilla chinensis in rat plasma. Rat plasma samples were pretreated by protein precipitation with methanol. The method validation was performed in accordance with US Food and Drug Administration guidelines and the results met the acceptance criteria. The method was successfully applied to assess the pharmacokinetics and oral bioavailability of Pulsatilla saponin D in rats. Copyright © 2014 John Wiley & Sons, Ltd.

  7. Hematological dosimetry

    International Nuclear Information System (INIS)

    Fluery-Herard, A.

    1991-01-01

    The principles of hematological dosimetry after acute or protracted whole-body irradiation are reviewed. In both cases, over-exposure is never homogeneous and the clinical consequences, viz medullary aplasia, are directly associated with the mean absorbed dose and the seriousness and location of the overexposure. The main hematological data required to assess the seriousness of exposure are the following: repeated blood analysis, blood precursor cultures, as indicators of whole-body exposure; bone marrow puncture, medullary precursor cultures and medullary scintigraphy as indicators of the importance of a local over-exposure and capacity for spontaneous repair. These paraclinical investigations, which are essential for diagnosis and dosimetry, are also used for surveillance and for the main therapeutic issues [fr

  8. Glipizide Pharmacokinetics in Healthy and Diabetic Volunteers

    African Journals Online (AJOL)

    Erah

    Purpose: Disease state may contribute to alteration in drug pharmacokinetics. The purpose of .... dependency or drug abuse, known allergy to ... HPLC analysis of glipizide ... months when stored at 4 0C, protected from .... plasma and urine.

  9. Comparison of high-pressure liquid chromatography and microbiological assay for determination of ciprofloxacin tablets in human plasma employed in bioequivalence and pharmacokinetics study.

    Science.gov (United States)

    Khan, Muhammad Khalid; Khan, Muhammad Farid; Mustafa, Ghulam; Sualah, Mohammed

    2012-01-01

    Ciprofloxacin was given orally to 28 healthy male volunteers for single oral dose of 500mg; Plasma samples were collected at different time's interval between 0 and 12h and analyzed both by high pressure liquid chromatography and by a microbiological assay. The detection limits (LOD) were 0.02μg/ml and 0.1μg/ml, for both methods respectively. For each method, coefficients of variation (R(2)) were 0.9995 and 0.9918 in plasma and limit of quantitation (LOQ).02 and 0.5μg/ml. The Comparison of means maximum concentration 2.68 μg/ml at 1.5 hr for test and 2.43 μg/ml are attain in HPLC method of Reference at 2hrs respectively. The plasma concentrations measured by microbiological assay of reference tablet are 3.95μg/ml (mean ± SE) at 1 hour and 3.80μg/ml (mean ± SE) at 1 hour. The concentrations in plasma measured by microbiological method were markedly higher than the high-pressure liquid chromatography values which indicates the presence of antimicrobially active metabolites. The mean ± SE values of pharmacokinetic parameters calculated by HPLC method, for total area under the curve (AUC 0-oo) were 13.11, and 11.91 h.mg/l for both test and reference tablets respectively. The mean ± SE values of clearance measured in l/h were 44.91 and 48.42 respectively. The elimination rate constant Kel [l/h] showed 0.17 l/h for test and 0.15 l/h reference tablets and likewise, absorption half-life expressed in hours shown 0.67 h for test and 1.04 h for reference respectively. The Mean Residence Time for test is 5.48 h and 5.49 h for reference. The mean ± SE values of pharmacokinetic parameters (Microbiological assay) for total area under the curve (AUC 0-oo) were 22.11 and 19.33 h.mg/l for both test and reference tablets respectively. The mean ± SE values of clearance measured in l/h were 29.02 and 31.63 respectively. The elimination rate constant Kel [l/h] showed 0.21 l/h for test and 0.20 l/h reference tablets and likewise, absorption half-life expressed in hours shown

  10. Simultaneous Determination of Decursin, Decursinol Angelate, Nodakenin, and Decursinol of Angelica gigas Nakai in Human Plasma by UHPLC-MS/MS: Application to Pharmacokinetic Study

    Directory of Open Access Journals (Sweden)

    Sook-Jin Kim

    2018-04-01

    Full Text Available Coumarins in Cham-dang-gwi, the dried root of Angelica gigas Nakai (AGN, possess pharmacological effects on anemia, pain, infection, and articular rheumatism. The AGN root containes decursin (D, decursinol angelate (DA, nodakenin, and decursinol (DOH, a major metabolite of D and DA. The aim of this study was to develop a simultaneous determination method for these four coumarins in human plasma using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS. Chromatographic separation was performed on dual columns (Kinetex® C18 column and Capcell core C18 column with mobile phase consisting of water and acetonitrile at a flow rate of 0.3 mL/min using gradient elution. Multiple reaction monitoring was operated in positive ion mode with precursors to product ion transition values of m/z 328.9→228.8, 328.9→228.9, 409.4→248.8, and 246.8→212.9 to measure D, DA, nodakenin, and DOH, respectively. Linear calibration curves were fitted over concentration range of 0.05–50 ng/mL for these four components, with correlation coefficient greater than 0.995. Inter- and intra-day accuracies were between 90.60% and 108.24%. These precisions were within 11.19% for all components. The established method was then applied to a pharmacokinetic study for the four coumarins after usual dosing in Korean subjects.

  11. Development of an LC/MS/MS method in order to determine arctigenin in rat plasma: its application to a pharmacokinetic study.

    Science.gov (United States)

    Zou, Quanfei; Gu, Yuan; Lu, Rong; Zhang, Tiejun; Zhao, Guang-Rong; Liu, Changxiao; Si, Duanyun

    2013-09-01

    In this study, a simple and sensitive LC/MS/MS method was developed and validated for the determination of arctigenin in rat plasma. The MS detection was performed using multiple reaction monitoring at the transitions of m/z 373.2 → 137.3 for arctigenin and m/z 187.1 → 131.0 for psoralen (internal standard) with a Turbo IonSpray electrospray in positive mode. The calibration curves fitted a good linear relationship over the concentration range of 0.2-500 ng/mL. It was found that arctigenin is not stable enough at both room temperature and -80 °C unless mixed with methanol before storage. The validated LC/MS/MS method was successfully applied for the pharmacokinetic study of arctigenin in rats. After intravenous injection of 0.3 mg/kg arctigenin injection to rats, the maximum concentration, half-life and area under the concentration-time curve were 323 ± 65.2 ng/mL, 0.830 ± 0.166 and 81.0 ± 22.1 h ng/mL, respectively. Copyright © 2013 John Wiley & Sons, Ltd.

  12. Liquid chromatographic method for the simultaneous determination of cefalexin and trimethoprim in dog plasma and application to the pharmacokinetic studies of a coformulated preparation.

    Science.gov (United States)

    Qi, Meiling; Wang, Peng; Sun, Ping; Liu, Xia

    2006-03-07

    A liquid chromatographic method is described for the simultaneous determination of cefalexin and trimethoprim in dog plasma. A simple protein precipitation procedure was adopted for the sample preparation with satisfactory extraction recoveries for both analytes. Chromatographic separation of the analytes was achieved on a C(18) column using a mixture of 2 mol/l formate buffer (pH 3.5), methanol and acetonitrile (22:7:7, v/v/v) containing a 0.002 mol/l sodium dodecyl sulfate as mobile phase and detection was performed at 240 nm. The linearity was obtained over the concentration ranges of 1.0-100.0 microg/ml for cefalexin and 0.5-50.0 microg/ml for trimethoprim. For each level of QC samples including the lower limit of quantification, both inter- and intra-day precisions (R.S.D.) were trimethoprim, and accuracy (RE) was -1.4% for cefalexin and -3.0% for trimethoprim. The present LC method was successfully applied to the pharmacokinetic studies of coformulated cefalexin dispersible tablets after oral administration to beagle dogs.

  13. LC-ESI-MS/MS determination of 4-methylpyrazole in dog plasma and its application to a pharmacokinetic study in dogs.

    Science.gov (United States)

    Chandrasekhar, Devaraj V; Suresh, Ponnayyan Sulochana; Dittakavi, Sreekanth; Hiremath, Rakesh A; Bhamidipati, Ravi Kanth; Richter, Wolfgang; Srinivas, Nuggehally R; Mullangi, Ramesh

    2018-02-01

    A simple, specific, sensitive and rapid LC-ESI-MS/MS method has been developed and validated for the quantification of 4-methylpyrazole in dog plasma using N-methylnicotinamide-d 4 as an internal standard (IS) as per regulatory guidelines. Sample preparation was accomplished through a simple protein precipitation. Chromatographic separation of 4-methylpyrazole and the IS was performed on a monolithic (Chromolith RP 18e ) column using an isocratic mobile phase comprising 0.2% formic acid in water and acetonitrile (20:80, v/v) at a flow rate of 1.0 mL/min. Elution of 4-methylpyrazole and the IS occurred at ~1.60 and 1.56 min, respectively. The total chromatographic run time was 3.2 min. A linear response function was established in the concentration range of 4.96-4955 ng/mL. The intra- and inter-day accuracy and precision were in the ranges 1.81-12.9 and 3.80-11.1%, respectively. This novel method has been applied to a pharmacokinetic study in dogs. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Determination of human insulin in dog plasma by a selective liquid chromatography-tandem mass spectrometry method: Application to a pharmacokinetic study.

    Science.gov (United States)

    Dong, Shiqi; Zeng, Yong; Wei, Guangli; Si, Duanyun; Liu, Changxiao

    2018-03-01

    A simple, sensitive and selective LC-MS/MS method for quantitative analysis of human insulin was developed and validated in dog plasma. Insulin glargine was used as the internal standard. After a simple step of solid-phase extraction, the chromatographic separation of human insulin was achieved by using InertSustain Bio C18 column with a mobile phase of acetonitrile containing 1% formic acid (A)-water containing 1% formic acid (B). The detection was performed by positive ion electrospray ionization in multiple-reaction monitoring (MRM) mode. Good linearity was observed in the concentration range of 1-1000 μIU/mL (r 2  > 0.99), and the lower limit of quantification was 1 μIU/mL (equal to 38.46 pg/mL). The intra- and inter-day precision (expressed as relative standard deviation, RSD) of human insulin were ≤12.1% and ≤13.0%, respectively, and the accuracy (expressed as relative error, RE) was in the range of -7.23-11.9%. The recovery and matrix effect were both within acceptable limits. This method was successfully applied for the pharmacokinetic study of human insulin in dogs after subcutaneous administration. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Simultaneous LC-MS/MS determination of five tripterygium pyridine alkaloids in dog plasma and its application to their pharmacokinetic study after oral administration of tripterygium glycosides tablets.

    Science.gov (United States)

    Su, Meng-xiang; Song, Min; Yang, Da-song; Shi, Jin-fang; Di, Bin; Hang, Tai-jun

    2015-05-15

    A sensitive and selective liquid chromatography tandem mass spectrometric method was developed and validated for the simultaneous determination of five pyridine alkaloids contained in tripterygium glycosides tablets (triptolide, wilforine, wilforgine, wilfording and wilfortrine) in dog plasma. The analysis was carried out on a Sepax GP-Phenyl column using a mixture of methanol and 10mmol/L ammonium formate buffer solution containing 0.1% formic acid (75:25, v/v) as the mobile phase pumped at a flow-rate of 1.0mL/min. All MS data were obtained in the positive ESI mode with selective multiple reaction monitoring of ion transitions. The method was fully validated to be accurate and precise with a linear range of 0.2-1000ng/mL for triptolide and 0.05-1000ng/mL for the other four pyridine alkaloids. The intra-day and inter-day precisions (relative standard deviation, RSD, %) were within 10.6% and 14.0%, respectively, and the relative error (RE, %) were all less than 13.1%. The method was successfully applied to multi-components pharmacokinetic study of the five pyridine alkaloids in beagle dogs after a single oral administration of 3mg/kg and 30mg/kg tripterygium glycosides tablets, respectively, and a multiple oral administration of 30mg/kg for 6 consecutive days. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Quantification of a Novel Photosensitizer of Chlorin e6-C15-Monomethyl Ester in Beagle Dog Plasma Using HPLC: Application to Pharmacokinetic Studies

    Directory of Open Access Journals (Sweden)

    Xiuxiu Li

    2017-04-01

    Full Text Available Chlorin e6-C15-monomethyl ester (CMME is a novel photosensitizer, which is synthetized from the degradation products of silkworm excrement. Preclinical studies on the promising photosensitizer CMME are necessary to determine its therapeutic efficacy and druglikeness. A high-performance liquid chromatography with UV detection (HPLC–UV method was established for the determination of CMME in beagle dog plasma. The sample preparation involved a protein-precipitation method with acetonitrile after the addition of tanshinone IIA as an internal standard (IS. CMME and the IS were separated on a Diamonsil C18 (2 column (100 mm × 4.6 mm, 5 μm with a isocratic system of methanol–water containing 20 mM ammonium acetate with 0.3% glacial acetic acid (85:15, v/v. The flow rate was 1.0 mL/min with UV detection using a wavelength of 400 nm. The method was sensitive enough with a lower limit of quantitation (LLOQ of 0.05 μg/mL and had a good linearity (r2 > 0.999 over the linear range of 0.05–5.00 μg/mL. The intra-day and inter-day accuracies ranged from 98.5% to 102.8% and precisions (RSD were within 6.8%. The validated method was successfully applied to the pharmacokinetic study of CMME after intravenous administration of single and multiple doses in beagle dogs.

  17. Evaluation of Tumor Angiogenesis Using Dynamic Enhanced Magnetic Resonance Imaging: Comparison of Plasma Vascular Endothelial Growth Factor, Hemodynamic, and Pharmacokinetic Parameters

    International Nuclear Information System (INIS)

    Ikeda, O.; Nishimura, R.; Miyayama, H.; Yasunaga, T.; Ozaki, Y.; Tuji, A.; Yamashita, Y.

    2004-01-01

    Purpose: To assess whether tumor angiogenesis of breast cancers can be predicted on the basis of dynamic magnetic resonance imaging (MRI). Material and Methods: Seventy-one patients with 71 breast cancers underwent Gd-DTPA enhanced dynamic MRI. Two regions of interest measurements were obtained in the periphery and in the center of the breast cancers. Hemodynamic parameters obtained by dynamic MRI included peak time, contrast enhancement ratio (CE ratio), and washout ratio. The triexponential concentration curve of Gd-DTPA was fitted to a theoretical model based on compartmental analysis. The transfer constant (or permeability surface product per unit volume of compartment 'k') was obtained using this method. Tumor angiogenesis was assessed by plasma vascular endothelial growth factor (P-VEGF). Results: The P-VEGF was positive in 28 of 71 tumors (39%). The CE ratio, washout ratio, and k in the periphery in P-VEGF positive breast cancers (mean 178%, 18%, and 1.5x10 -2 (s-1)) were significantly greater (P -2 (s-1)). The peak time in the periphery in P-VEGF positive breast cancers was more marked than for P-VEGF negative breast cancers, but this difference was not significant. Conclusion: The hemodynamic and pharmacokinetic analysis of MRI provides valuable information about angiogenesis of breast cancers

  18. Rapid sensitive validated UPLC–MS method for determination of venlafaxine and its metabolite in rat plasma: Application to pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Dubey

    2013-12-01

    Full Text Available A new ultra-performance liquid chromatography–electrospray ionization mass spectrometry (UPLC–MS/ESI method for simultaneous determination of venlafaxine (VEN and its metabolite O-desmethylvenlafaxine (ODV in rat plasma has been developed and validated using Venlafaxine d6 as the internal standard. The compounds and internal standard were extracted from plasma by solid phase extraction. The UPLC separation of the analytes was performed on ACQUITY UPLC® BEH Shield RP18 (1.7 µm, 100 mm×2.1 mm column, using isocratic elution with mobile phase constituted of water (containing 2 mM ammonium acetate: acetonitrile (20:80, v/v at a flow rate of 0.3 mL/min. All of the analytes were eluted within 1.5 min. The compounds were ionized in the electrospray ionization (ESI ion source of the mass spectrometer, operating in multiple reaction monitoring (MRM and positive ion mode. The precursor to product ion transitions monitored for VEN, ODV and Venlafaxine d6 were m/z 278.3→121.08, 264.2→107.1 and 284.4→121.0, respectively. The developed and validated method was used for the pharmacokinetic study of VEN in rats. Keywords: Venlafaxine, O-desmethylvenlafaxine, Metabolite, UPLC–MS/ES

  19. Development and validation of a high performance liquid chromatography quantification method of levo-tetrahydropalmatine and its metabolites in plasma and brain tissues: application to a pharmacokinetic study.

    Science.gov (United States)

    Abdallah, Inas A; Huang, Peng; Liu, Jing; Lee, David Y; Liu-Chen, Lee-Yuan; Hassan, Hazem E

    2017-04-01

    Levo-tetrahydropalmatine (l-THP) is an alkaloid isolated from Chinese medicinal herbs of the Corydalis and Stephania genera. It has been used in China for more than 40 years mainly as an analgesic with sedative/hypnotic effects. Despite its extensive use, its metabolism has not been quantitatively studied, nor there a sensitive reliable bioanalytical method for its quantification simultaneously with its metabolites. As such, the objective of this study was to develop and validate a sensitive and selective HPLC method for simultaneous quantification of l-THP and its desmethyl metabolites l-corydalmine (l-CD) and l-corypalmine (l-CP) in rat plasma and brain tissues. Rat plasma and brain samples were processed by liquid-liquid extraction using ethyl acetate. Chromatographic separation was achieved on a reversed-phase Symmetry® C 18 column (4.6 × 150 mm, 5 μm) at 25°C. The mobile phase consisted of acetonitrile-methanol-10 mm ammonium phosphate (pH 3) (10:30:60, v/v) and was used at a flow rate of 0.8 mL/min. The column eluent was monitored at excitation and emission wavelengths of 230 and 315 nm, respectively. The calibration curves were linear over the concentration range of 1-10,000 ng/mL. The intra- and interday reproducibility studies demonstrated accuracy and precision within the acceptance criteria of bioanalytical guidelines. The validated HPLC method was successfully applied to analyze samples from a pharmacokinetic study of l-THP in rats. Taken together, the developed method can be applied for bioanalysis of l-THP and its metabolites in rodents and potentially can be transferred for bioanalysis of human samples. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Salting-Out Assisted Liquid-Liquid Extraction for Quantification of Febuxostat in Plasma Using RP-HPLC and Its Pharmacokinetic Application.

    Science.gov (United States)

    Tandel, Devang; Shah, Purvi; Patel, Kalpana; Thakkar, Vaishali; Patel, Kirti; Gandhi, Tejal

    2016-11-01

    A rapid and sensitive reversed-phase high-performance liquid chromatography (HPLC) method using novel salting-out assisted liquid-liquid extraction technique has been developed for the quantitative determination of febuxostat (FEB), used for the treatment of gout, in rat plasma. The method was validated according to US FDA guideline. Separation was achieved using a Phenomenex Luna-C 18 (250 × 4.60 mm, 5 µm) column and mobile phase composed of potassium dihydrogen orthophosphate buffer 25 mM, adjusted to pH 6.8 with triethylamine:methanol in a ratio of 35:65 (v/v) showing retention time 5.56 and 8.86 min for FEB and internal standard, respectively. The optimal salting-out parameters; 1 mL of acetonitrile and 200 µL of 2 M ammonium acetate salt showed extraction recovery >90% for FEB from plasma. This extraction procedure afforded clear samples resulting in convenient and cost-saving procedure and showed good linear relationship (r > 0.9997) between peak area ratio and concentration from 0.3 to 20 µg/mL. The results of pharmacokinetic study showed that absorption profile of spherical agglomerate of FEB compared to marketed formulation was higher indicating greater systemic absorption. In conclusion, the developed SALLE-HPLC method with simple ultraviolet detection offered a number of advantages including good quantitative ability, wide linear range, high recovery, short analysis time as well as low cost. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Plasma and pleural fluid pharmacokinetics of erlotinib and its active metabolite OSI-420 in patients with non-small-cell lung cancer with pleural effusion.

    Science.gov (United States)

    Masago, Katsuhiro; Togashi, Yosuke; Fukudo, Masahide; Terada, Tomohiro; Irisa, Kaoru; Sakamori, Yuichi; Kim, Young Hak; Mio, Tadashi; Inui, Ken-Ichi; Mishima, Michiaki

    2011-09-01

    Erlotinib is orally active and selectively inhibits the tyrosine kinase activity of the epidermal growth factor receptor. The pleural space penetration and exposure of erlotinib is poorly understood. Thus, we investigated the pharmacokinetics (PK) of erlotinib and its active metabolite OSI-420 in non-small-cell lung cancer (NSCLC) of malignant pleural effusion (MPE). We analyzed the PK of erlotinib and OSI-420 on days 1 and 8 after beginning erlotinib therapy in 9 patients with MPE. Their concentrations were determined by high-performance liquid chromatography with ultraviolet detection. Blood samples were obtained five times per day: before administration, and 2, 4, 8, and 24 hours after administration. Pleural effusions were obtained once per day, 2 hours after administration on day 1, and before administration on day 8. The exceptions were cases 2 and 4, which had pleural effusions obtained just before drug administration, and 2, 4, 8, and 24 hours after administration. The mean percentage of penetration from plasma to pleural effusion for erlotinib was 18% on day 1 and 112% on day 8, while these values for OSI-420 were 9.5% on day 1 and 131% on day 8. The area under the drug concentration-time curve of pleural fluid for erlotinib was 28,406 ng-hr/mL for case 2 and 45,906 ng-hr/mL for case 4. There seems to be a significant accumulation of both erlotinib and OSI-420 in MPE with repeated dosing. Although larger studies will be necessary to determine the true impact of erlotinib MPE accumulation on plasma PK and safety, erlotinib can be administered safely to patients with MPE with respect to efficacy and side effects. Copyright © 2011. Published by Elsevier Inc.

  2. Enantioselective determination of (R)- and (S)-lansoprazole in human plasma by chiral liquid chromatography with mass spectrometry and its application to a stereoselective pharmacokinetic study.

    Science.gov (United States)

    Sun, Luning; Cao, Yang; Jiao, Huiwen; Fang, Yunqian; Yang, Zhicheng; Bian, Mingliang; Zhang, Hongwen; Gong, Xiaojian; Wang, Yongqing

    2015-11-01

    A simple and enantioselective method was developed and validated for the simultaneous determination of (R)- and (S)-lansoprazole in human plasma by chiral liquid chromatography with tandem mass spectrometry. Lansoprazole enantiomers and internal standard (esomeprazole) were extracted from plasma using acetonitrile as protein precipitating agent. Baseline chiral separation was achieved within 9.0 min on a Chiralpak IC column (150 mm × 4.6 mm, 5 μm) with the column temperature of 30°C. The mobile phase consisted of 10 mM ammonium acetate solution containing 0.05% acetic acid/acetonitrile (50:50, v/v). The mass spectrometric analysis was performed using a QTrap 5500 mass spectrometer coupled with an electrospray ionization source in positive ion mode. The multiple reactions monitoring transitions of m/z 370.1→252.1 and 346.1→198.1 were used to quantify lansoprazole enantiomers and esomeprazole, respectively. For each enantiomer, no apparent matrix effect was found, the calibration curve was linear over 5.00-3000 ng/mL, the intra- and inter-day precisions were below 10.0%, and the accuracy was -3.8 to 3.3%. Analytes were stable during the study. No chiral inversion was observed during sample storage, preparation procedure and analysis. The method was applied to the stereoselective pharmacokinetic studies in human after intravenous administration of dexlansoprazole or racemic lansoprazole. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. A Sensitive and Robust Ultra HPLC Assay with Tandem Mass Spectrometric Detection for the Quantitation of the PARP Inhibitor Olaparib (AZD2281 in Human Plasma for Pharmacokinetic Application

    Directory of Open Access Journals (Sweden)

    Jeffrey Roth

    2014-06-01

    Full Text Available Olaparib (AZD2281 is an orally active PARP-1 inhibitor, primarily effective against cancers with BRCA1/2 mutations. It is currently in Phase III development and has previously been investigated in numerous clinical trials, both as a single agent and in combination with chemotherapy. Despite this widespread testing, there is only one published method that provides assay details and stability studies for olaparib alone. A more sensitive uHPLC-MS/MS method for the quantification of olaparib in human plasma was developed, increasing the range of quantification at both ends (0.5–50,000 ng/mL compared to previously published methods (10–5,000 ng/mL. The wider range encompasses CMAX levels produced by typical olaparib doses and permits better pharmacokinetic modeling of olaparib elimination. This assay also utilizes a shorter analytical runtime, allowing for more rapid quantification and reduced use of reagents. A liquid-liquid extraction was followed by chromatographic separation on a Waters UPLC® BEH C18 column (2.1 × 50 mm, 1.7 µm and mass spectrometric detection. The mass transitions m/z 435.4→281.1 and m/z 443.2→281.1 were used for olaparib and the internal standard [2H8]-olaparib, respectively. The assay proved to be accurate (<9% deviation and precise (CV < 11%. Stability studies showed that olaparib is stable at room temperature for 24 h. in whole blood, at 4 °C for 24 h post-extraction, at −80 °C in plasma for at least 19 months, and through three freeze-thaw cycles. This method proved to be robust for measuring olaparib levels in clinical samples from a Phase I trial.

  4. Analysis of fenretinide and its metabolites in human plasma by liquid chromatography-tandem mass spectrometry and its application to clinical pharmacokinetics.

    Science.gov (United States)

    Cho, Hwang Eui; Min, H Kang

    2017-01-05

    A simple and accurate high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of N-(4-hydroxyphenyl)retinamide (fenretinide, 4-HPR) and its metabolites, 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR) and N-(4-methoxyphenyl)retinamide (4-MPR), in human plasma. Plasma samples were prepared using protein precipitation with ethanol. Chromatographic separation of the three analytes and N-(4-ethoxyphenyl)retinamide (4-EPR), an internal standard, was achieved on a Zorbax SB-C18 column (3.5μm, 50×2.1mm) using gradient elution with the mobile phase of 0.1% formic acid in water and acetonitrile (pH* 2.4) at a flow rate of 0.5mL/min. Electrospray ionization (ESI) mass spectrometry was operated in the positive ion mode with multiple reaction monitoring (MRM). The calibration curves obtained were linear over the concentration range of 0.2-50ng/mL with a lower limit of quantification of 0.2ng/mL. The relative standard deviation of intra-day and inter-day precision was below 7.64%, and the accuracy ranged from 94.92 to 105.43%. The extraction recoveries were found to be higher than 90.39% and no matrix effect was observed. The analytes were stable for the durations of the stability studies. The validated method was successfully applied to the analyses of the pharmacokinetic study for patients treated with 4-HPR in a clinical trial. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Development and Validation of a LC/MS/MS Method for the Determination of Duloxetine in Human Plasma and Its Application to Pharmacokinetic Study

    Directory of Open Access Journals (Sweden)

    D. Chandrapal Reddy

    2012-01-01

    Full Text Available A selective, high sensitive and high throughput liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS method has been developed and validated for the chromatographic separation and quantitation of duloxetine in human EDTA plasma using fluoxetine (IS as an internal standard. Analyte and IS were extracted from human plasma by liquid-liquid extraction using MTBE-n Hexane (80:20.The eluted samples were chromatographed on X-terra RP8 (50 mmx4.6 mm, 5 μm particle size column by using mixture of 30 mM ammonium formate (pH-5.0±0.05 and acetonitrile as an isocratic mobile phase at a flow rate of 0.40 mL/min and analyzed by mass spectrometer in the multiple reaction monitoring (MRM using the respective m/z 298.08→154.0 for duloxetine and 310.02→148.07 for IS. The linearity of the response/ concentration curve was established in human plasma over the concentration range 0.100-100.017 ng/mL. The lower detection limit (LOD,S/N>3 was 0.04 ng/mL and the lower limit of quantization (LOQ,S/N>10 was 0.100 ng/mL. This LC-MS/MS method was validated with Intra-batch and Inter-batch precision of 5.21-7.02. The Intra-batch and Inter-batch accuracy was 97.14-103.50 respectively. Recovery of duloxetine in human plasma is 80.31% and ISTD recovery is 81.09%. The main pharmacokinetic parameters were Tmax (hr = (7.25±1.581, Cmax (ng/mL (44.594±18.599, AUC0→t, = (984.702±526.502 and AUC0→∞, (1027.147±572.790 respectively.

  6. PHARMACOKINETICS AND PHARMACOKINETIC DYNAMIC RELATIONSHIP OF ROCURONIUM BROMIDE IN HUMANS

    NARCIS (Netherlands)

    WIERDA, JMKH; PROOST, JH; SCHIERE, S; HOMMES, FDM

    The existing human pharmacokinetic studies have been reviewed and compared with data derived from animals. The earliest study confirms the similarity of rocuronium to vecuronium with respect to the variables derived from the plasma concentration decay curves and the proportion excreted renally.

  7. Population pharmacokinetics of piperacillin in the early phase of septic shock – does standard dosing result in therapeutic plasma concentrations?

    DEFF Research Database (Denmark)

    Öbrink-Hansen, Kristina Margareta; Juul, Rasmus Vestergaard; Storgaard, Merete

    2015-01-01

    using NONMEM and data was best described by a two-compartment model. Central and inter-compartmental clearances were 3.6 L/h (RSE 15.7%) and 6.58 (16.4%), and central and peripheral volumes were 7.3 L (RSE 11.8 %) and 3.9 L (RSE 9.7%), respectively. Piperacillin plasma concentrations varied considerably...

  8. Analysis of oxcarbazepine and the 10-hydroxycarbazepine enantiomers in plasma by LC-MS/MS: application in a pharmacokinetic study.

    Science.gov (United States)

    de Jesus Antunes, Natalicia; Wichert-Ana, Lauro; Coelho, Eduardo Barbosa; Della Pasqua, Oscar; Alexandre, Veriano; Takayanagui, Osvaldo Massaiti; Tozatto, Eduardo; Lanchote, Vera Lucia

    2013-12-01

    Oxcarbazepine is a second-generation antiepileptic drug indicated as monotherapy or adjunctive therapy in the treatment of partial seizures or generalized tonic-clonic seizures in adults and children. It undergoes rapid presystemic reduction with formation of the active metabolite 10-hydroxycarbazepine (MHD), which has a chiral center at position 10, with the enantiomers (S)-(+)- and R-(-)-MHD showing similar antiepileptic effects. This study presents the development and validation of a method of sequential analysis of oxcarbazepine and MHD enantiomers in plasma using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Aliquots of 100 μL of plasma were extracted with a mixture of methyl tert-butyl ether: dichloromethane (2:1). The separation of oxcarbazepine and the MHD enantiomers was obtained on a chiral phase Chiralcel OD-H column, using a mixture of hexane:ethanol:isopropanol (80:15:5, v/v/v) as mobile phase at a flow rate of 1.3 mL/min with a split ratio of 1:5, and quantification was performed by LC-MS/MS. The limit of quantification was 12.5 ng oxcarbazepine and 31.25 ng of each MHD enantiomer/mL of plasma. The method was applied in the study of kinetic disposition of oxcarbazepine and the MHD enantiomers in the steady state after oral administration of 300 mg/12 h oxcarbazepine in a healthy volunteer. The maximum plasma concentration of oxcarbazepine was 1.2 µg/mL at 0.75 h. The kinetic disposition of MHD is enantioselective, with a higher proportion of the S-(+)-MHD enantiomer compared to R-(-)-MHD and an AUC(0-12) S-(+)/R-(-) ratio of 5.44. © 2013 Wiley Periodicals, Inc.

  9. HPLC method for determination of biologically active epoxy-transformers of treosulfan in human plasma: pharmacokinetic application.

    Science.gov (United States)

    Główka, Franciszek K; Romański, Michał; Teżyk, Artur; Zaba, Czesław; Wróbel, Tomasz

    2012-03-25

    Clinical trials demonstrated treosulfan (TREO) as a promising myeloablative agent prior to hematopoietic stem cell transplantation (HSCT). TREO is a specific pro-drug from which biologically active mono- (S,S-EBDM) and diepoxybutane (S,S-DEB) derivatives are formed in vitro or in vivo by a non-enzymatic pH and temperature-dependent intramolecular nucleophilic substitution. Following extraction of the plasma samples with a mixture of dichloromethane and acetonitrile, S,S-EBDM and S,S-DEB were derivatized with 3-nitrobenzenesulfonic acid (3-NBS) to UV-absorbing esters. Optimal temperature and time of derivatization as well as extraction method and also the effect of pH on TREO stability in plasma were established. Identity of the synthesized derivatives was confirmed by mass spectrometry. The post-derivatization mixture was purified from the excess of unreacted 3-NBS by extraction with water. The derivatization products and 2,2'-dinitrobiphenyl (internal standard) were separated on Nucleosil 100 C18 column using a mobile phase consisted of acetonitrile and water. The developed method was validated and demonstrated adequate accuracy and precision. Limit of quantification for both S,S-EBDM and S,S-DEB amounted to 2.5 μM. The method was applied in clinical conditions to quantify the levels of TREO activation products in plasma of children undergoing HSCT. The methodology for simultaneous determination of TREO epoxy-transformers in human plasma is described for the first time. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. A rapid, LC-MS/MS assay for quantification of piperacillin and tazobactam in human plasma and pleural fluid; application to a clinical pharmacokinetic study.

    Science.gov (United States)

    Popowicz, Natalia D; O'Halloran, Sean J; Fitzgerald, Deirdre; Lee, Y C Gary; Joyce, David A

    2018-04-01

    Piperacillin, in combination with tazobactam is a common first-line antibiotic used for the treatment of pleural infection, however its pleural pharmacokinetics and penetration has not previously been reported. The objective of this work was to develop and validate a rapid and sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay for quantification of piperacillin (PIP) and tazobactam (TAZ). PIP and TAZ were extracted from both human plasma and pleural fluid samples by protein precipitation in methanol containing the internal standards (IS) piperacillin-d 5 (PIP-d 5 ) and sulbactam (SUL). Briefly, 5 μL of sample was mixed with 125 μL of methanol containing IS, vortexed and centrifuged. Supernatant (50 μL) was diluted into 500 μL of mobile phase containing 10 mM of ammonium bicarbonate in LCMS grade water and transferred to the autosampler tray. Electrospray ionization in positive mode and multiple reaction monitoring (MRM) were used for PIP and PIP-d 5 at the transitions m/z 518.2 → 143.2 and m/z 523.2 → 148.2 respectively, and electrospray ionization in negative mode and MRM were used for TAZ and SUL at the transitions m/z 299.1 → 138.1 and m/z 232.4 → 140.1. The chromatographic separation was achieved using an Acquity BEH C-18 column with gradient elution of mobile phase containing 10 mmol/L ammonium bicarbonate in water and methanol. A linear range was observed over the concentration range of 0.25-352 mg/L and 0.25-50.5 mg/L for PIP and TAZ respectively. Complete method validation was performed according to US FDA guidelines for selectivity, specificity, precision and accuracy, LLOQ, matrix effects, recovery and stability, with all results within acceptable limits. This method was successfully applied to two patients with pleural infection and is suitable for further pharmacokinetic studies and therapeutic drug monitoring. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  11. Comparison of pharmacokinetic behavior of two iridoid glycosides in rat plasma after oral administration of crude Cornus officinals and its jiuzhipin by high performance liquid chromatography triple quadrupole mass spectrometry combined with multiple reactions monitoring mode

    Science.gov (United States)

    Chen, Xiaocheng; Cao, Gang; Jiang, Jianping

    2014-01-01

    Objective: The present study examined the pharmacokinetic profiles of two iridoid glycosides named morroniside and loganin in rat plasma after oral administration of crude and processed Cornus officinals. Materials and Methods: A rapid, selective and specific high-performance liquid chromatography/electrospray ionization tandem mass spectrometry with multiple reactions monitoring mode was developed to simultaneously investigate the pharmacokinetic profiles of morroniside and loganin in rat plasma after oral administration of crude C. officinals and its jiuzhipin. Results: The morroniside and loganin in crude and processed C. officinals could be simultaneously determined within 7.4 min. Linear calibration curves were obtained over the concentration ranges of 45.45-4800 ng/mL for all the analytes. The intra-and inter-day precisions relative standard deviation was lesser than 2.84% and 4.12%, respectively. Conclusion: The pharmacokinetic parameters of two iridoid glucosides were also compared systematically between crude and processed C. officinals. This paper provides the theoretical proofs for further explaining the processing mechanism of Traditional Chinese Medicines. PMID:24914290

  12. Population pharmacokinetics/pharmacodynamics of erlotinib and pharmacogenomic analysis of plasma and cerebrospinal fluid drug concentrations in Japanese patients with non-small cell lung cancer.

    Science.gov (United States)

    Fukudo, Masahide; Ikemi, Yasuaki; Togashi, Yosuke; Masago, Katsuhiro; Kim, Young Hak; Mio, Tadashi; Terada, Tomohiro; Teramukai, Satoshi; Mishima, Michiaki; Inui, Ken-Ichi; Katsura, Toshiya

    2013-07-01

    Erlotinib shows large inter-patient pharmacokinetic variability, but the impact of early drug exposure and genetic variations on the clinical outcomes of erlotinib remains fully investigated. The primary objective of this study was to clarify the population pharmacokinetics/pharmacodynamics of erlotinib in Japanese patients with non-small cell lung cancer (NSCLC). The secondary objective was to identify genetic determinant(s) for the cerebrospinal fluid (CSF) permeability of erlotinib and its active metabolite OSI-420. A total of 88 patients treated with erlotinib (150 mg/day) were enrolled, and CSF samples were available from 23 of these patients with leptomeningeal metastases. Plasma and CSF concentrations of erlotinib and OSI-420 were measured by high-performance liquid chromatography with UV detection. Population pharmacokinetic analysis was performed with the nonlinear mixed-effects modelling program NONMEM. Germline mutations including ABCB1 (1236C>T, 2677G>T/A, 3435C>T), ABCG2 (421C>A), and CYP3A5 (6986A>G) polymorphisms, as well as somatic EGFR activating mutations if available, were examined. Early exposure to erlotinib and its safety/efficacy relationship were evaluated. The apparent clearance of erlotinib and OSI-420 were significantly decreased by 24 and 35 % in patients with the ABCG2 421A allele, respectively (p OSI-420 (p model showed that erlotinib trough (C0) levels on day 8 were an independent risk factor for the development of grade ≥2 diarrhea (p = 0.037) and skin rash (p = 0.031). Interstitial lung disease (ILD)-like events occurred in 3 patients (3.4 %), and the median value of erlotinib C0 levels adjacent to these events was approximately 3 times higher than that in patients who did not develop ILD (3253 versus 1107 ng/mL; p = 0.014). The objective response rate in the EGFR wild-type group was marginally higher in patients achieving higher erlotinib C0 levels (≥1711 ng/mL) than that in patients having lower erlotinib C0

  13. Neutron Dosimetry

    International Nuclear Information System (INIS)

    Vanhavere, F.

    2001-01-01

    The objective of SCK-CEN's R and D programme on neutron dosimetry is to improve the determination of neutron doses by studying neutron spectra, neutron dosemeters and shielding adaptations. In 2000, R and D focused on the contiued investigation of the bubble detectors type BD-PND and BDT, in particular their sensitivity and temperature dependence; the updating of SCK-CEN's criticality dosemeter, the investigation of the characteristics of new thermoluminescent materials and their use in neutron dosemetry; and the investigation of neutron shielding

  14. Neutron Dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Vanhavere, F

    2001-04-01

    The objective of SCK-CEN's R and D programme on neutron dosimetry is to improve the determination of neutron doses by studying neutron spectra, neutron dosemeters and shielding adaptations. In 2000, R and D focused on the contiued investigation of the bubble detectors type BD-PND and BDT, in particular their sensitivity and temperature dependence; the updating of SCK-CEN's criticality dosemeter, the investigation of the characteristics of new thermoluminescent materials and their use in neutron dosemetry; and the investigation of neutron shielding.

  15. A C8-Modified Graphene@mSiO2 Composites Based Method for Quantification of Gallic Acid in Rat Plasma after Oral Administration of Changtai Granule and Its Application to Pharmacokinetics.

    Science.gov (United States)

    Xu, Chen; Yu, Yingjia; Ling, Li; Wang, Yang; Zhang, Jundong; Li, Yan; Duan, Gengli

    2017-01-01

    A rapid, effective extraction technique has been established for measuring the gallic acid in rat plasma by using sandwich-structured graphene/mesoporous silica composites with C 8 -modified interior pore-walls as adsorbent. The unique characteristics of the graphene-silica composites excluded large molecules, like proteins, from the mesopore channels as a result of size exclusion effect, leading to a direct extraction of drug molecules from protein-rich biological samples such as plasma without any other pretreatment procedure. Followed by elution and centrifugation, the gallic acid-absorbed composites were rapidly isolated before LC-MS/MS. Serving as a reliable tool for analysis of Traditional Chinese Medicine: Changtai Granule, the newly developed method was fully validated and successfully applied in the pharmacokinetic study of gallic acid in rat plasma. Extraction recovery, matrix effect and stability were satisfactory in rat plasma. According to the results of pharmacokinetic studies, Changtai Granule exhibited greater adsorption, distribution and clearance properties of gallic acid in the treatment of ulcerative colitis. Hence, this study may offer a valuable alternative to simplify and speed up sample preparation, and be useful for clinical studies of related preparations.

  16. Development of good modelling practice for phsiologically based pharmacokinetic models for use in risk assessment: The first steps

    Science.gov (United States)

    The increasing use of tissue dosimetry estimated using pharmacokinetic models in chemical risk assessments in multiple countries necessitates the need to develop internationally recognized good modelling practices. These practices would facilitate sharing of models and model eva...

  17. Plasma pharmacokinetics, tissue distribution and excretion of MnDPDP in the rat and dog after intravenous administration

    International Nuclear Information System (INIS)

    Hustvedt, S.O.

    1997-01-01

    Purpose: To investigate distribution and excretion of mangafodipir (MnDPDP, Teslascan) in the rat and dog. Material and Methods: Formulations of either 14 C-MnDPDP or 54 MnDPDP were injected intravenously at near clinical doses in rats and dogs. Results: The manganese (Mn) moeity is rapidly removed from plasma with an elimination half-life of less than 25 min in both species, reflecting a rapid distribution to the tissues and an early excretion. The plasma clearance of the DPDP moeity is slower than that of Mn and it appears to distribute into the extracellular fluid. Mn is distributed largely to the liver, pancreas and kidneys, and in pregnant rats, also to foetal liver and bones. No transplacental passage of DPDP could be detected. The metal is mainly excreted by the faecal route, with a small fraction eliminated early in the urine. DPDP is rapidly and essentially completely excreted in the urine, consistent with the glomerular filtration rate. (orig./AJ)

  18. Pharmacokinetics of Enrofloxacin and Danofloxacin in Plasma, Inflammatory Exudate, and Bronchial Secretions of Calves following Subcutaneous Administration

    Science.gov (United States)

    McKellar, Quintin; Gibson, Ian; Monteiro, Ana; Bregante, Miguel

    1999-01-01

    Enrofloxacin (2.5 mg/kg of body weight) and danofloxacin (1.25 mg/kg) were administered subcutaneously to ruminating calves (n = 8) fitted with subcutaneous tissue cages. Concentrations of enrofloxacin, its metabolite ciprofloxacin, and danofloxacin in blood (plasma), tissue cage exudate (following intracaveal injection of 0.3 ml of 1% [vol/wt] carrageenan), and bronchial secretions were measured by high-performance liquid chromatography (HPLC) and microbiological assay (enrofloxacin plus ciprofloxacin and danofloxacin). Mean maximum concentrations (Cmax) ± standard deviations of enrofloxacin (0.24 ± 0.08 μg/ml), ciprofloxacin (0.11 ± 0.03 [total, 0.34 ± 0.10] μg/ml), and danofloxacin (0.23 ± 0.05 μg/ml) were detected in the plasma of calves by HPLC. The Cmax were 0.49 ± 0.17 μg/ml (enrofloxacin equivalents) and 0.24 ± 0.03 μg/ml (danofloxacin) when they were measured by microbiological assay. Mean Cmax in exudate (HPLC) were 0.18 ± 0.07 μg/ml (enrofloxacin), 0.10 ± 0.04 μg/ml (ciprofloxacin), 0.27 ± 0.09 μg/ml (enrofloxacin plus ciprofloxacin), and 0.19 ± 0.05 μg/ml (danofloxacin), and concentrations in exudate exceeded those in plasma from 8 h (enrofloxacin and ciprofloxacin) or 6 h (danofloxacin) after drug administration. The Cmax were 0.34 ± 0.09 μg/ml (enrofloxacin equivalents) and 0.22 ± 0.04 μg/ml (danofloxacin) in exudate when they were measured by the microbiological assay. The maximum mean concentration achieved in bronchial secretions (HPLC) were 0.07 ± 0.04 μg/ml (enrofloxacin), 0.04 ± 0.07 μg/ml (ciprofloxacin), 0.10 ± 0.05 μg/ml (enrofloxacin plus ciprofloxacin), and 0.12 ± 0.09 μg/ml (danofloxacin). The maximum mean concentration in bronchial secretions from a limited number of animals from which samples were available for microbiological assay were 0.27 ± 0.11 μg/ml (n = 4 [enrofloxacin equivalents]) and 0.14 ± 0.02 μg/ml (n = 3 [danofloxacin]). With predictive models of efficacy (Cmax/MIC and area under the

  19. Topics in radiation dosimetry radiation dosimetry

    CERN Document Server

    1972-01-01

    Radiation Dosimetry, Supplement 1: Topics in Radiation Dosimetry covers instruments and techniques in dealing with special dosimetry problems. The book discusses thermoluminescence dosimetry in archeological dating; dosimetric applications of track etching; vacuum chambers of radiation measurement. The text also describes wall-less detectors in microdosimetry; dosimetry of low-energy X-rays; and the theory and general applicability of the gamma-ray theory of track effects to various systems. Dose equivalent determinations in neutron fields by means of moderator techniques; as well as developm

  20. Pharmacokinetic study and interaction with the reticulo-endothelial system of a plasma substitute: modified fluid gelatine

    International Nuclear Information System (INIS)

    Vie, M.-T.

    1973-01-01

    By the labelling of a plasma substitute prepared from gelatine, MFG or modified fluid gelatine, it was possible to establish certain facts concerning the kinetics of MFG and its action on the cells of the reticulo-endothelial system. Iodine labelling proved sufficiently reliable to allow the pharmakokinetic exploration of the product by a method which, being relatively simple to use, offers good reproducibility of results. Various tests on the strength of the iodine protein bond showed the stability of the entire protein molecule. A study of the metabolism revealed that the MFG in question behaves towards the organism not as a pure substance but as a mixture of two molecular species of different mass. The experimental results concerning the influence of MFG on the reticulo-endothelial system showed that the phagocyte function is only modified if there is competition between the phagocyted molecule and the MFG [fr

  1. Determination of metabolite of nicergoline in human plasma by high-performance liquid chromatography and its application in pharmacokinetic studies

    Directory of Open Access Journals (Sweden)

    Rong Zheng

    2012-02-01

    Full Text Available A fast, simple and sensitive high performance liquid chromatographic (HPLC method has been developed for determination of 10α-methoxy-6-methyl ergoline-8β-methanol (MDL, a main metabolite of nicergoline in human plasma. One-step liquid–liquid extraction (LLE with diethyl ether was employed as the sample preparation method. Tizanidine hydrochloride was selected as the internal standard (IS. Analysis was carried out on a Diamonsil ODS column (150 mm×4.6 mm, 5 μm using acetonitrile–ammonium acetate (0.1 mol/L (15/85, v/v as mobile phase at detection wavelength of 224 nm. The calibration curves were linear over the range of 2.288–73.2 ng/mL with a lower limit of quantitation (LLOQ of 2.288 ng/mL. The intra- and inter-day precision values were below 13% and the recoveries were from 74.47% to 83.20% at three quality control levels. The method herein described was successfully applied in a randomized crossover bioequivalence study of two different nicergoline preparations after administration of 30 mg in 20 healthy volunteers. Keywords: Nicergoline, 10α-methoxy-6-methylergoline-8β-methanol (MDL, HPLC, Plasma-drug concentration, Bioequivalence study

  2. Determination of the phytochemical composition of Jingning fang and the in vivo pharmacokinetics of its metabolites in rat plasma by UPLC-MS/MS.

    Science.gov (United States)

    Yang, Chunjing; Yin, XingBin; Dong, Xiaoxv; Zhang, Xin; You, Longtai; Wang, Wenping; Wang, Junhong; Chen, Qinghe; Ni, Jian

    2017-11-01

    Jingning fang (JNF) is an effective Traditional Chinese Medicine (TCM) which is used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). To clarify the bioactive constituents of JNF, a Thermo Q Exactive™ Plus Orbitrap™ mass spectrometer was used in this study. More than 127 chemical compounds were isolated and identified tentatively in the JNF extract, while 42 prototype constituents with 4 potential metabolites were identified tentatively in rat plasma. A method for simultaneous determination of polygalaxanthone III (PAIII), sibiricose A 5 (A 5 ), sibiricose A 6 (A 6 ), 3, 6'-disinapoyl sucrose (3,6'-DISS), tenuifoliside C (TEC), tenuifolin B (TNB), verbascoside (VCE), heterophyllin B (HEB) and schisandrin (SCH) in rat was developed and validated using polydatin (PLN) and psoralen (PSN) as internal standards. All calibration curves proved favorable linearity (R 2 ≥0.9923) in linear ranges. The lower limit of quantification (LLOQ) was 2.5ng/mL for PAIII, A 5 , 3, 6'-DISS, TNB, VCE, HEB and SCH, 1.0ng/mL for A 6 and TEC, respectively. Intra-day and inter-day precisions didn't exceed 14.0% for all the analytes. Extraction recoveries and matrix effects of analytes and IS were acceptable. The validated method has been successfully applied to the pharmacokinetics (PK) studies of the nine compounds in JNF. These findings are useful for predicting the bioactive components of JNF, and will aid in optimizing dose regimens of the drug. Copyright © 2017. Published by Elsevier B.V.

  3. A Systematic Analysis of the Sensitivity of Plasma Pharmacokinetics to Detect Differences in the Pulmonary Performance of Inhaled Fluticasone Propionate Products Using a Model-Based Simulation Approach.

    Science.gov (United States)

    Weber, Benjamin; Hochhaus, Guenther

    2015-07-01

    The role of plasma pharmacokinetics (PK) for assessing bioequivalence at the target site, the lung, for orally inhaled drugs remains unclear. A validated semi-mechanistic model, considering the presence of mucociliary clearance in central lung regions, was expanded for quantifying the sensitivity of PK studies in detecting differences in the pulmonary performance (total lung deposition, central-to-peripheral lung deposition ratio, and pulmonary dissolution characteristics) between test (T) and reference (R) inhaled fluticasone propionate (FP) products. PK bioequivalence trials for inhaled FP were simulated based on this PK model for a varying number of subjects and T products. The statistical power to conclude bioequivalence when T and R products are identical was demonstrated to be 90% for approximately 50 subjects. Furthermore, the simulations demonstrated that PK metrics (area under the concentration time curve (AUC) and C max) are capable of detecting differences between T and R formulations of inhaled FP products when the products differ by more than 20%, 30%, and 25% for total lung deposition, central-to-peripheral lung deposition ratio, and pulmonary dissolution characteristics, respectively. These results were derived using a rather conservative risk assessment approach with an error rate of <10%. The simulations thus indicated that PK studies might be a viable alternative to clinical studies comparing pulmonary efficacy biomarkers for slowly dissolving inhaled drugs. PK trials for pulmonary efficacy equivalence testing should be complemented by in vitro studies to avoid false positive bioequivalence assessments that are theoretically possible for some specific scenarios. Moreover, a user-friendly web application for simulating such PK equivalence trials with inhaled FP is provided.

  4. Chiral analysis of bambuterol, its intermediate and active drug in human plasma by liquid chromatography-tandem mass spectrometry: Application to a pharmacokinetic study.

    Science.gov (United States)

    Zhou, Ting; Liu, Shan; Zhao, Ting; Zeng, Jing; He, Mingzhi; Xu, Beining; Qu, Shanshan; Xu, Ling; Tan, Wen

    2015-08-01

    A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for simultaneous chiral analysis of an antiasthma drug bambuterol, its key intermediate monocarbamate bambuterol and its active drug terbutaline in human plasma. All samples were extracted with ethyl acetate and separated on an Astec Chirobiotic T column under isocratic elution with a mobile phase consisting of methanol and water with the addition of 20mm ammonium acetate and 0.005% (v/v) formic acid at 0.6mL/min. The analytes were detected by a Xevo TQ-S tandem mass spectrometer with positive electrospray ionization in multiple reaction monitoring mode. The established method has high sensitivity with the lower limit of quantifications of 25.00pg/mL for bambuterol enantiomers, and 50.00pg/mL for monocarbamate bambuterol and terbutaline enantiomers, respectively. The calibration curves for bambuterol enantiomers were linear in the range of 25.00-2500pg/mL, and for monocarbamate bambuterol and terbutaline enantiomers were linear in the range of 50.00-5000pg/mL. The intra- and inter-day precisions were <12.4%. All the analytes were separated in 18.0min. For the first time, the validated method was successfully applied to an enantioselective pharmacokinetic study of rac-bambuterol in 8 healthy volunteers. According to the results, this chiral LC-MS/MS assay provides a suitable and robust method for the enantioselectivity and interaction study of the prodrug bambuterol, the key intermediate monocarbamate bambuterol and its active drug terbutaline in human. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Determination of a natural DNMT1 inhibitor, peperomin E, in rat plasma by UFLC-MS/MS and method application in a pharmacokinetic study.

    Science.gov (United States)

    Wang, Xin-Zhi; Wen, Hong-Mei; Chai, Chuan; Zhang, Wen-Ying; Gao, Ming; Liu, Rui; Wu, Hao; Liang, Jing-Yu

    2017-08-01

    Peperomin E (PepE), a naturally occurring secolignan isolated from Peperomia dindygulensis, has drawn much attention recently owing to its anticancer and DNA methyltransferase 1 (DNMT1) inhibitory activity. Here, a simple and sensitive ultra-fast liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of PepE in rat plasma for the first time. Samples were prepared by simple protein precipitation. Separation was performed on an XBridge™ C 18 column using a mobile phase of acetonitrile and 0.1% (v/v) aqueous formic acid. PepE and the internal standard arctigenin were detected in a positive-ion mode using multiple reaction monitoring of the transitions at m/z 413.2 → 261.0 and 373.2 → 137.2, respectively. The calibration curve for PepE was linear over the range of concentrations of 1.46-6000 ng/mL, with a lower limit of quantitation of 1.46 ng/mL. Both intra- and interday precisions were within 11.05%, and the accuracy ranged from -11.5 to 5.51%. The extraction recovery and matrix effect were within acceptable limits. Stability tests showed that PepE remained stable throughout the analytical procedure. The validated method was then used to analyze the pharmacokinetics of PepE administered to rats orally (12.5 and 25 mg/kg) or intravenously (6.25 and 12.5 mg/kg). Copyright © 2017 John Wiley & Sons, Ltd.

  6. Development of a rapid and sensitive UPLC-MS/MS assay for the determination of TM-2 in beagle dog plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Lin, Hongli; Zhao, Yunli; Men, Lei; Yang, Mingjing; Liu, Hui; Shao, Yanjie; Wang, Pei; Tang, Xing; Yu, Zhiguo

    2015-01-01

    A simple and sensitive method based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed for the determination of TM-2, which was a novel semi-synthetic taxane derivative in beagle dog plasma. Cabazitaxel was chosen as internal standard. Following extraction by methyl tert-butyl ether, the chromatographic separation was achieved on a Thermo Syncronis C18 column (50 × 2.1 mm, 1.7 µm) by gradient elution within a runtime of 3.5 min. The mobile phase consisted of (A) acetonitrile and (B) 2 mmol/L ammonium acetate in water. The detection was accomplished using positive ion electrospray ionization in multiple reaction monitoring mode. The MS/MS ion transitions were monitored at m/z 812.39 → 551.35 for TM-2 and 836.36 → 555.26 for IS, respectively. The method was linear for TM-2 (r = 0.9924) ranging from 2.5 to 1000 ng/mL. The intra-day and inter-day precisions (relative standard deviation) were within 8.0 and 17.6%, respectively, and the accuracy (relative error) was less than 2.3%. The extraction recovery ranged from 83.1 to 97.1%. The reliable method was successfully applied to a pharmacokinetic study of TM-2 in beagle dogs after intravenous drip with different doses of 0.6, 1.2, and 2.4 mg/kg, respectively. Copyright © 2014 John Wiley & Sons, Ltd.

  7. Simultaneous determination of clevidipine and its primary metabolite in dog plasma by liquid chromatography-tandem mass spectrometry: Application to pharmacokinetic study.

    Science.gov (United States)

    Zhou, Ying; Li, Huqun; He, Xiaomeng; Jia, Mengmeng; Ni, Yang; Xu, Mingzhen; Chen, Hui; Li, Weiyong

    2014-11-01

    A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of clevidipine and its primary metabolite H152/81 in dog plasma after protein precipitation with acetonitrile using felodipine as the internal standard (IS). Chromatographic separation was performed on a XB C18 column (2.1mm×50mm, 3.5μm) under isocratic conditions with the mobile phase consisting of acetonitrile and 20mM ammonium acetate buffer (pH 7.0) (40:60, v/v) at the flow rate of 0.3ml/min. The run time was 5.5min. Mass spectrometric analysis was performed on a triple quadrupole mass spectrometer operated in the multiple reaction monitoring (MRM) mode with the transitions of m/z 473.0→338.2 for clevidipine, m/z 356.1→324.0 for H152/81 and m/z 383.9→338.2 for the IS. The method was fully validated in terms of selectivity, linearity, lower limit of quantification (LLOQ), accuracy, precision, stability, matrix effect and recovery over a concentration range of 0.15-200ng/ml for clevidipine and 10-2000ng/ml for H152/81, respectively. The analytical method was applied to support a pharmacokinetic study of simultaneous determination of clevidipine and H152/81 in ten healthy beagle dogs. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. LC-MS/MS method for the simultaneous determination of PA-824, moxifloxacin and pyrazinamide in rat plasma and its application to pharmacokinetic study.

    Science.gov (United States)

    Wang, Libin; Xu, Yue; Liang, Li; Diao, Chunyan; Liu, Xueying; Zhang, Jianchun; Zhang, Shengyong

    2014-08-01

    A simple, sensitive and rapid LC-MS/MS method has been developed and validated for simultaneous determination of PA-824, moxifloxacin, and pyrazinamide in rat plasma using metronidazole as internal standard. Sample preparation involved a simple one-step protein precipitation with methanol, followed by centrifugation and evaporation of the organic solvent. The residue was redissolved in mobile phase and analyzed by LC-MS/MS. An Inertsil(®) ODS3 C18 column (150mm×4.6mm, 5μm), a mobile phase composed of methanol-0.03% TEA (triethylamine) in water (85:15, v/v), and a flow rate of 0.5mL/min were employed, and the total run time was 6.0min. The mass spectrometer was run in positive ion ESI-APCI combined mode using multiple reaction monitoring (MRM) to monitor the mass transitions. The method was validated for accuracy, precision, linearity, range, selectivity, lower limit of quantification (LLOQ), recovery, and matrix effect. All validation parameters met the acceptance criteria according to regulatory guidelines. The LLOQ was 1.0μg/mL for pyrazinamide and 0.1μg/mL for PA-824 and moxifloxacin. The recoveries obtained for PA-824, moxifloxacin and pyrazinamide were ≥85%. Intra-day and inter-day coefficients of variation were less than 10%. The method had been successfully applied to a pharmacokinetic study of fixed dose administration of PA-824, moxifloxacin, pyrazinamide and their combination in SD rat. Significant differences of Tmax, Cmax, AUC(0-t) and CLz/F were observed between the single and combined groups after equal dose of PA-824 and moxifloxacin administration, which revealed the possibility of drug-drug interaction (DDI) between the PaMZ combination. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Ofloxacin pharmacokinetics in renal failure.

    OpenAIRE

    Fillastre, J P; Leroy, A; Humbert, G

    1987-01-01

    The pharmacokinetics of ofloxacin were investigated in 12 normal subjects and 21 uremic patients after the administration of a single oral 200-mg dose. An open three-compartment body model was used to calculate ofloxacin pharmacokinetic parameters. In healthy subjects, the peak plasma level averaged 2.24 +/- 0.90 micrograms/ml and was obtained at 0.83 +/- 0.31 h. The absorption rate constant was 4.22 +/- 1.64 h-1. The terminal half-life was 7.86 +/- 1.81 h. The apparent volume of distribution...

  10. Pharmacokinetics of Cannabinoids

    Directory of Open Access Journals (Sweden)

    Iain J McGilveray

    2005-01-01

    Full Text Available Delta-9-tetrahydrocannabinol (Δ-9-THC is the main psychoactive ingredient of cannabis (marijuana. The present review focuses on the pharmacokinetics of THC, but also includes known information for cannabinol and cannabidiol, as well as the synthetic marketed cannabinoids, dronabinol (synthetic THC and nabilone. The variability of THC in plant material (0.3% to 30% leads to variability in tissue THC levels from smoking, which is, in itself, a highly individual process. THC bioavailability averages 30%. With a 3.55% THC cigarette, a peak plasma level of 152±86.3 ng/mL occured approximately 10 min after inhalation. Oral THC, on the other hand, is only 4% to 12% bioavailable and absorption is highly variable. THC is eliminated from plasma in a multiphasic manner, with low amounts detectable for over one week after dosing. A major active 11-hydroxy metabolite is formed after both inhalation and oral dosing (20% and 100% of parent, respectively. THC is widely distributed, particularly to fatty tissues, but less than 1% of an administered dose reaches the brain, while the spleen and body fat are long-term storage sites. The elimination of THC and its many metabolites (from all routes occurs via the feces and urine. Metabolites persist in the urine and feces for severalweeks. Nabilone is well absorbed and the pharmacokinetics, although variable, appear to be linear from oral doses of 1 mg to 4 mg (these doses show a plasma elimination half-life of approximately 2 h. As with THC, there is a high first-pass effect, and the feces to urine ratio of excretion is similar to other cannabinoids. Pharmacokineticpharmacodynamic modelling with plasma THC versus cardiac and psychotropic effects show that after equilibrium is reached, the intensity of effect is proportional to the plasma THC profile. Clinical trials have found that nabilone produces less tachycardia and less euphoria than THC for a similar antiemetic response.

  11. High-performance liquid chromatographic method for the determination and pharmacokinetic study of oxypeucedanin hydrate and byak-angelicin after oral administration of Angelica dahurica extracts in mongrel dog plasma.

    Science.gov (United States)

    Xie, Ying; Chen, Yi; Lin, Mei; Wen, Jun; Fan, Guorong; Wu, Yutian

    2007-05-09

    A high-performance liquid chromatographic method was developed and validated for the determination and pharmacokinetic study of oxypeucedanin hydrate and byak-angelicin after oral administration of Angelica dahurica extracts in mongrel dog plasma. The coumarin components and the internal standard isopsoralen were extracted from plasma samples with the mixture of tert-butyl methyl ether and n-hexane (4:1, v/v). Chromatographic separation was performed on a C(18) column (200 mm x 4.6mm, 5 microm) with the mobile phase acetonitrile-methanol-water-acetic acid (20:15:65:2, v/v/v/v) at a flow-rate of 1.0 ml/min. Only the peak of oxypeucedanin hydrate and byak-angelicin could be detected in dog plasma after oral administration of ethanol extracts of A. dahurica mainly containing xanthotoxol, osthenol, imperatorin, oxypeucedanin hydrate and byak-angelicin. The calibration curves of oxypeucedanin hydrate and byak-angelicin were linear over a range of 22.08-8830.00 and 6.08-2430.00 ng/ml in dog plasma, respectively. The quantification limit of oxypeucedanin hydrate and byak-angelicin in dog plasma was 22.08 and 6.08 ng/ml, respectively. The intra- and inter-day precision was less than 7.6% and 8.5% and the accuracy was from 91.9% to 106.1%. The lowest absolute recoveries of oxypeucedanin hydrate and byak-angelicin were 85.7% and 87.0%, respectively. The method was successfully applied to the pharmacokinetic studies of oxypeucedanin hydrate and byak-angelicin in dog plasma after oral administration of ethanol extracts from A. dahurica.

  12. Development and validation of a high throughput LC–MS/MS method for simultaneous quantitation of pioglitazone and telmisartan in rat plasma and its application to a pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Pinaki Sengupta

    2017-12-01

    Full Text Available Management of cardiovascular risk factors in diabetes demands special attention due to their co-existence. Pioglitazone (PIO and telmisartan (TLM combination can be beneficial in effective control of cardiovascular complication in diabetes. In this research, we developed and validated a high throughput LC–MS/MS method for simultaneous quantitation of PIO and TLM in rat plasma. This developed method is more sensitive and can quantitate the analytes in relatively shorter period of time compared to the previously reported methods for their individual quantification. Moreover, till date, there is no bioanalytical method available to simultaneously quantitate PIO and TLM in a single run. The method was validated according to the USFDA guidelines for bioanalytical method validation. A linear response of the analytes was observed over the range of 0.005–10 µg/mL with satisfactory precision and accuracy. Accuracy at four quality control levels was within 94.27%–106.10%. The intra- and inter-day precision ranged from 2.32%–10.14 and 5.02%–8.12%, respectively. The method was reproducible and sensitive enough to quantitate PIO and TLM in rat plasma samples of a preclinical pharmacokinetic study. Due to the potential of PIO-TLM combination to be therapeutically explored, this method is expected to have significant usefulness in future. Keywords: LC–MS/MS, Rat plasma, Pharmacokinetic applicability, Telmisartan, Pioglitazone, Pharmacokinetic application

  13. Development and validation of an LC-MS/MS method for simultaneous quantification of levodopa and MD01 in rat plasma and its application to a pharmacokinetic study of mucuna pruriens extract.

    Science.gov (United States)

    Yang, Guangjie; Zhang, Fangrong; Deng, Linfang; Chen, Chang; Cheng, Zhongzhe; Huang, Jiangeng; Liu, Jiangyun; Jiang, Hongliang

    2016-09-01

    Mucuna pruriens, an ancient Indian herbal medicine containing levodopa, is widely used for Parkinson's disease. In order to simultaneously determine levodopa and 1,1-dimethyl-3-carboxy-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (MD01) in rat plasma, an improved LC-MS/MS method was developed and validated for a pharmacokinetic study in rats orally administered levodopa or Mucuna pruriens extract (MPE). Elimination of matrix effect and improvement of extraction recovery were achieved through systematic optimization of reversed-phase and hydrophilic interaction chromatographic conditions together with sample clean-up procedures. A satisfactory chromatographic performance was obtained with a Thermo Aquasil C18 column (50 × 2.1 mm, 3 µm) using acetonitrile and water containing 0.2% formic acid as mobile phases. Futhermore, sodium metabisulfite and formic acid were used as stabilizers in neat solutions as well as rat plasma. The method was validated in a dynamic range of 20.0-10,000 ng/mL for levodopa and MD01; the intra- and inter-day precision and accuracy were acceptable. The method was successfully utilized to determine the levodopa level in plasma samples of rats administered levodopa or MPE. Pharmacokinetic results showed that an increase in the AUC of levodopa was observed in rats following oral administration of multiple doses of MPE. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Development of a UPLC-MS/MS Method for Simultaneous Determination of Six Flavonoids in Rat Plasma after Administration of Maydis stigma Extract and Its Application to a Comparative Pharmacokinetic Study in Normal and Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Bin-Bin Wei

    2017-07-01

    Full Text Available Maydis stigma is an important medicine herb used in many parts of the world for treatment of diabetes mellitus, which main bioactive ingredients are flavonoids. This paper describes for the first time a study on the comparative pharmacokinetics of six active flavonoid ingredients of Maydis stigma in normal and diabetic rats orally administrated with the decoction. Therefore, an efficient and sensitive ultra high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS method for the simultaneous determination of six anti-diabetic ingredients (cynaroside, quercetin, luteolin, isorhamnetin, rutin and formononetin of Maydis stigma in rat plasma has been developed and validated in plasma samples, which showed good linearity over a wide concentration range (r2 > 0.99, and gave a lower limit of quantification of 1.0 ng·mL−1 for the analytes. The intra- and interday assay variability was less than 15% for all analytes. The mean extraction recoveries and matrix effect of analytes and IS from rats plasma were all more than 85.0%. The stability results showed the measured concentration for six analytes at three QC levels deviated within 15.0%. The results indicated that significant differences in the pharmacokinetic parameters of the analytes were observed between the two groups of animals, whereby the absorptions of these analytes in the diabetic group were all significantly higher than those in the normal group, which provides an experimental basis for the role of Maydis stigma in anti-diabetic treatment.

  15. Simultaneous quantitation of polygalaxanthone III and four ginsenosides by ultra-fast liquid chromatography with tandem mass spectrometry in rat and beagle dog plasma after oral administration of Kai-Xin-San: application to a comparative pharmacokinetic study.

    Science.gov (United States)

    Lv, Chunxiao; Li, Qing; Zhang, Xiaowen; He, Bosai; Xu, Huarong; Yin, Yidi; Liu, Ran; Liu, Jingjing; Chen, Xiaohui; Bi, Kaishun

    2014-05-01

    A fast, selective, and quantitative ultra-fast liquid chromatography with tandem mass spectrometry method has been developed and validated for the simultaneous quantitation of polygalaxanthone III, ginsenoside Rb1, ginsenoside Rd, ginsenoside Re, and ginsenoside Rg1 in the plasma of rat and beagle dog after oral administration of Kai-Xin-San. After addition of the internal standard, salidroside, the plasma samples were extracted by liquid-liquid extraction and separated on a Venusil MP C18 column with methanol/0.01% acetic acid water as mobile phase. The tandem mass spectrometric detection was performed in the multiple reaction monitoring with turbo ion spray source in a switching ionization mode. The method was examined, and found to be precise and accurate with the linearity range of the compounds. The intra- and interday precision and accuracy of the analytes were well within acceptance criteria (±15%). The mean extraction recoveries of analytes and internal standard were all >75.0%. The validated method has been successfully applied to comparing pharmacokinetic profiles of analytes in rat and beagle dog plasma. The results indicated that no significant differences were observed in pharmacokinetic parameters of ginsenoside Rg1, while the others had significant differences, which may due to the different mechanisms of absorption and metabolism. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Radiation dosimetry

    International Nuclear Information System (INIS)

    Harper, M.W.; Thomas, B.; Conway, J.

    1977-01-01

    A dosemeter is described that is based on the TSCD principle (thermally stimulated current dosimetry). Basically this involves irradiating a responsive material and then heating it,whereby an electric current is produced. If the material is heated in an electric field the peak value of the thermally stimulated current or alternatively the total charge released by heating, can be related to the radiation dose received. The instrument described utilises a sheet coated with a thermoplastic polymer, such as a poly4-methylpent-l-ene. The polymer should have a softening point not lower than 150 0 C with an electrical resistivity of at least 10 16 chms/cm at 150 0 C. The polymer may also be PTFE. Heating should be in the range 150 0 C to 200 0 C and the electric field in the range 50 to 10,000V/mm. (U.K.)

  17. Organ dosimetry

    International Nuclear Information System (INIS)

    Kaul, Dean C.; Egbert, Stephen D.; Otis, Mark D.; Kuhn, Thomas; Kerr, George D.; Eckerman, Keith F.; Cristy, Mark; Ryman, Jeffrey C.; Tang, Jabo S.; Maruyama, Takashi

    1987-01-01

    This chapter describes the technical approach, complicating factors, and sensitivities and uncertainties of calculations of doses to the organs of the A-bomb survivors. It is the object of the effort so described to provide data that enables the dosimetry system to determine the fluence, kerma, absorbed dose, and similar quantities in 14 organs and the fetus, specified as being of radiobiological interest. This object was accomplished through the use of adjoint Monte Carlo computations, which use a number of random particle histories to determine the relationship of incident neutrons and gamma rays to those transported to a target organ. The system uses these histories to correlate externally-incident energy- and angle-differential fluences with the fluence spectrum (energy differential only) within the target organ. In order for the system to work in the most efficient manner possible, two levels of data were provided. The first level, represented by approximately 6,000 random adjoint-particle histories, enables the computation of the fluence spectrum with sufficient precision to provide statistically reliable (± 6 %) mean doses within any given organ. With this limited history inventory, the system can be run rapidly for all survivors. Mean organ dose and dose uncertainty are obtainable in this mode. The second mode of operation enables the system to produce a good approximation to fluence spectrum within any organ or to produce the dose in each of an array of organ subvolumes. To be statistically reliable, this level of detail requires far more random histories, approximately 40,000 per organ. Thus, operation of the dosimetry system in this mode (i.e., with this data set) is intended to be on an as-needed, organ-specific basis, since the system run time is eight times that in the mean dose mode. (author)

  18. Estimation of placental and lactational transfer and tissue distribution of atrazine and its main metabolites in rodent dams, fetuses, and neonates with physiologically based pharmacokinetic modeling

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Zhoumeng [Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602 (United States); Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602 (United States); Fisher, Jeffrey W. [Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); Wang, Ran [Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762 (United States); Institute of Food Safety, Jiangsu Academy of Agricultural Sciences, Nanjing 210014 (China); Ross, Matthew K. [Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762 (United States); Filipov, Nikolay M., E-mail: filipov@uga.edu [Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602 (United States); Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602 (United States)

    2013-11-15

    Atrazine (ATR) is a widely used chlorotriazine herbicide, a ubiquitous environmental contaminant, and a potential developmental toxicant. To quantitatively evaluate placental/lactational transfer and fetal/neonatal tissue dosimetry of ATR and its major metabolites, physiologically based pharmacokinetic models were developed for rat dams, fetuses and neonates. These models were calibrated using pharmacokinetic data from rat dams repeatedly exposed (oral gavage; 5 mg/kg) to ATR followed by model evaluation against other available rat data. Model simulations corresponded well to the majority of available experimental data and suggest that: (1) the fetus is exposed to both ATR and its major metabolite didealkylatrazine (DACT) at levels similar to maternal plasma levels, (2) the neonate is exposed mostly to DACT at levels two-thirds lower than maternal plasma or fetal levels, while lactational exposure to ATR is minimal, and (3) gestational carryover of DACT greatly affects its neonatal dosimetry up until mid-lactation. To test the model's cross-species extrapolation capability, a pharmacokinetic study was conducted with pregnant C57BL/6 mice exposed (oral gavage; 5 mg/kg) to ATR from gestational day 12 to 18. By using mouse-specific parameters, the model predictions fitted well with the measured data, including placental ATR/DACT levels. However, fetal concentrations of DACT were overestimated by the model (10-fold). This overestimation suggests that only around 10% of the DACT that reaches the fetus is tissue-bound. These rodent models could be used in fetal/neonatal tissue dosimetry predictions to help design/interpret early life toxicity/pharmacokinetic studies with ATR and as a foundation for scaling to humans. - Highlights: • We developed PBPK models for atrazine in rat dams, fetuses, and neonates. • We conducted pharmacokinetic (PK) study with atrazine in pregnant mice. • Model predictions were in good agreement with experimental rat and mouse PK data

  19. Estimation of placental and lactational transfer and tissue distribution of atrazine and its main metabolites in rodent dams, fetuses, and neonates with physiologically based pharmacokinetic modeling

    International Nuclear Information System (INIS)

    Lin, Zhoumeng; Fisher, Jeffrey W.; Wang, Ran; Ross, Matthew K.; Filipov, Nikolay M.

    2013-01-01

    Atrazine (ATR) is a widely used chlorotriazine herbicide, a ubiquitous environmental contaminant, and a potential developmental toxicant. To quantitatively evaluate placental/lactational transfer and fetal/neonatal tissue dosimetry of ATR and its major metabolites, physiologically based pharmacokinetic models were developed for rat dams, fetuses and neonates. These models were calibrated using pharmacokinetic data from rat dams repeatedly exposed (oral gavage; 5 mg/kg) to ATR followed by model evaluation against other available rat data. Model simulations corresponded well to the majority of available experimental data and suggest that: (1) the fetus is exposed to both ATR and its major metabolite didealkylatrazine (DACT) at levels similar to maternal plasma levels, (2) the neonate is exposed mostly to DACT at levels two-thirds lower than maternal plasma or fetal levels, while lactational exposure to ATR is minimal, and (3) gestational carryover of DACT greatly affects its neonatal dosimetry up until mid-lactation. To test the model's cross-species extrapolation capability, a pharmacokinetic study was conducted with pregnant C57BL/6 mice exposed (oral gavage; 5 mg/kg) to ATR from gestational day 12 to 18. By using mouse-specific parameters, the model predictions fitted well with the measured data, including placental ATR/DACT levels. However, fetal concentrations of DACT were overestimated by the model (10-fold). This overestimation suggests that only around 10% of the DACT that reaches the fetus is tissue-bound. These rodent models could be used in fetal/neonatal tissue dosimetry predictions to help design/interpret early life toxicity/pharmacokinetic studies with ATR and as a foundation for scaling to humans. - Highlights: • We developed PBPK models for atrazine in rat dams, fetuses, and neonates. • We conducted pharmacokinetic (PK) study with atrazine in pregnant mice. • Model predictions were in good agreement with experimental rat and mouse PK data.

  20. New Modified UPLC/Tandem Mass Spectrometry Method for Determination of Risperidone and Its Active Metabolite 9-Hydroxyrisperidone in Plasma: Application to Dose-Dependent Pharmacokinetic Study in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Essam Ezzeldin

    2017-01-01

    Full Text Available Sensitive and specific liquid-chromatography tandem mass spectrometry (UPLC-MS/MS assay has been developed and validated for simultaneous quantification of risperidone (RIS and its active metabolite 9-hydroxyrisperidone (9-OH-RIS in rat plasma using olanzapine (OLA as internal standard (IS. Pharmacokinetics of risperidone and its active metabolite 9-hydroxyrisperidone was compared across different doses (0.3, 1.0, and 6.0 mg/kg. Serial blood sample was collected over a time of 48 hours and analyzed for risperidone and its active metabolite 9-hydroxyrisperidone. The pharmacokinetics parameters including Cmax, tmax, and AUC were determined for risperidone and its active ingredient. The method was linear in the concentration range of 0.2–500 ng/mL for risperidone and 9-OH-risperidone, with coefficients of determination greater than 0.998 and lower limit of quantitation of 0.2 ng/mL. Blood levels of risperidone and its active metabolite were roughly dose-proportional. The method developed herein is simple and rapid and was successfully applied for dose-dependent pharmacokinetic study.

  1. Simultaneous determination of paeoniflorin, albiflorin, ferulic acid, tetrahydropalmatine, protopine, typhaneoside, senkyunolide I in Beagle dogs plasma by UPLC-MS/MS and its application to a pharmacokinetic study after Oral Administration of Shaofu Zhuyu Decoction.

    Science.gov (United States)

    Huang, Xiaochen; Su, Shulan; Cui, Wenxia; Liu, Pei; Duan, Jin-ao; Guo, Jianming; Li, Zhenhao; Shang, Erxin; Qian, Dawei; Huang, Zhijun

    2014-07-01

    In this present study, a sensitive and rapid UPLC-MS/MS method was developed for simultaneous quantification of paeoniflorin, albiflorin, ferulic acid, tetrahydropalmatine, protopine, typhaneoside and senkyunolide I in Beagle dog plasma after oral administration of the Shao-Fu-Zhu-Yu Decoction. Chloramphenicol and clarithromycin were used as internal standards. Plasma samples were processed by protein precipitation with methanol. The separation was performed on an Acquity BEH C18 column (100mm×2.1mm, 1.7μm) at a flow-rate of 0.4mL/min, using 0.1% formic acid-acetonitrile as mobile phase. Method validation was performed as per Food and Drug Administration guidelines and the results met the acceptance criteria. After validation, this method was successfully applied to a pharmacokinetic study. The results showed that the apparent plasma clearance of paeoniflorin, albiflorin, typhaneoside and senkyunolide I were significantly higher than others. Double peak was observed in plasma concentration curves of tetrahydropalmatine, the ferulic acid had a good absorption in Beagle dog plasma, and senkyunolide I was detected in plasma from the first blood sampling time (15min) and rapidly reached Tmax. The compound of typhaneoside has a low bioavailability according to the results. Copyright © 2014. Published by Elsevier B.V.

  2. Simultaneous determination of andrographolide, dehydroandrographolide and neoandrographolide in dog plasma by LC-MS/MS and its application to a dog pharmacokinetic study of Andrographis paniculata tablet.

    Science.gov (United States)

    Xu, Fang-fang; Fu, Shu-jun; Gu, Sheng-pan; Wang, Zhi-min; Wang, Zhen-zhong; He, Xin; Xiao, Wei

    2015-05-15

    In this study, a sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determinate andrographolide (AP), dehydroandrographolide (DP), and neoandrographolide (NP) in plasma of beagle dogs after oral administration of Andrographis paniculata tablet (A. paniculata). The analytes and bilobalide (internal standard) were separated on an Agilent ZORBAX XDB-C18 column (50mm×2.1mm, 3.5μm) by using gradient elution consisting of methanol and water at a flow rate of 0.50mL/min in 7min. Multiple reaction monitoring (MRM) mode was performed to quantify data under monitoring precursor-product ion transitions of m/z 348.8→286.9, 330.9→107.9, 479.1→160.8 and 325.0→163.0 for AP, DP, NP and internal standard (IS) at negative ion mode, respectively. This method was developed at linearity ranging from 0.50 to 250ng/mL for AP, 1.00 to 500ng/mL for DP and 0.20 to 100ng/mL for NP. The accuracy of each analyte ranged between 94.8% and 107.1% and the precision was within 14.6%. No significant matrix effect was observed. AP, DP and NP were stable during sample storage, preparation and analytic procedures. Furthermore, this method was successfully applied in the investigation of the pharmacokinetic profile of AP, DP and NP in beagle dogs after oral administration of A. paniculata tablet (49.5mg for AP, 7.0mg for DP, 22.0mg for NP). Biological half-life (t1/2) was 2.08±0.99, 3.13±1.19 and 1.07±0.38h for AP, DP and NP, respectively. The areas under curves (AUC0-t) of AP, DP and NP was 494.50±150.64, 26.01±8.72 and 78.78±18.29ngh/mL, respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Personnel neutron dosimetry

    International Nuclear Information System (INIS)

    Hankins, D.

    1982-04-01

    This edited transcript of a presentation on personnel neutron discusses the accuracy of present dosimetry practices, requirements, calibration, dosemeter types, quality factors, operational problems, and dosimetry for a criticality accident. 32 figs

  4. Dosimetry for radiation processing

    DEFF Research Database (Denmark)

    Miller, Arne

    1986-01-01

    During the past few years significant advances have taken place in the different areas of dosimetry for radiation processing, mainly stimulated by the increased interest in radiation for food preservation, plastic processing and sterilization of medical products. Reference services both...... and sterilization dosimetry, optichromic dosimeters in the shape of small tubes for food processing, and ESR spectroscopy of alanine for reference dosimetry. In this paper the special features of radiation processing dosimetry are discussed, several commonly used dosimeters are reviewed, and factors leading...

  5. Simultaneous determination of five free and total flavonoids in rat plasma by ultra HPLC-MS/MS and its application to a comparative pharmacokinetic study in normal and hyperlipidemic rats.

    Science.gov (United States)

    Wang, Xiaofan; Zhao, Xu; Gu, Liqiang; Lv, Chunxiao; He, Bosai; Liu, Zhenzhen; Hou, Pengyi; Bi, Kaishun; Chen, Xiaohui

    2014-03-15

    A simple and rapid ultra-high performance liquid chromatography-tandem mass spectrometry (uHPLC-MS/MS) method has been developed for the simultaneous determination of five free flavonoids (amentoflavone, isorhamnetin, naringenin, kaempferol and quercetin) and their total (free and conjugated) forms, and to compare the pharmacokinetics of these active ingredients in normal and hyperlipidemic rats. The free and total forms of these flavonoids were extracted by liquid-liquid extraction with ethyl acetate. The conjugated flavonoids were deconjugated by the enzyme β-Glucuronidase and Sulfatase. Chromatographic separation was accomplished on a ZORBAX Eclipse XDB-C8 USP L7 column using gradient elution. Detection was performed on a 4000Q uHPLC-MS/MS system from AB Sciex using negative ion mode in the multiple reaction monitoring (MRM) mode. The lower limits of quantification were 2.0-5.0ng/mL for all the analytes. Intra-day and inter-day precision were less than 15% and accuracy ranged from -9.3% to 11.0%, and the mean extraction recoveries of analytes and internal standard (IS) from rat plasma were all more than 81.7%. The validated method was successfully applied to a comparative pharmacokinetic study of five free and total analytes in rat plasma. The results indicated that the absorption of five total flavonoids in hyperlipidemia group were significantly higher than those in normal group with similar concentration-time curves. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Neutron dosimetry - A review

    Energy Technology Data Exchange (ETDEWEB)

    Baum, J W

    1955-03-29

    This review summarizes information on the following subjects: (1) physical processes of importance in neutron dosimetry; (2) biological effects of neutrons; (3) neutron sources; and (4) instruments and methods used in neutron dosimetry. Also, possible improvements in dosimetry instrumentation are outlined and discussed. (author)

  7. Simultaneous quantification of preactivated ifosfamide derivatives and of 4-hydroxyifosfamide by high performance liquid chromatography-tandem mass spectrometry in mouse plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Deroussent, Alain; Skarbek, Charles; Maury, Adeline; Chapuis, Hubert; Daudigeos-Dubus, Estelle; Le Dret, Ludivine; Durand, Sylvère; Couvreur, Patrick; Desmaële, Didier; Paci, Angelo

    2015-06-15

    The antitumor drug, ifosfamide (IFO), requires activation by cytochrome P450 (CYP) to form the active metabolite, 4-hydroxyisfosfamide (4-OHIFO), leading to toxic by-products at high dose. In order to overcome these drawbacks, preactivated ifosfamide derivatives (RXIFO) were designed to release 4-OHIFO without CYP involvement. A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the simultaneous quantification of 4-OHIFO, IFO and four derivatives RXIFO in mouse plasma using multiple reaction monitoring. Because of its instability in plasma, 4-OHIFO was immediately converted to the semi-carbazone derivative, 4-OHIFO-SCZ. For the six analytes, the calibration curves were linear from 20 to 5000ng/mL in 50μL plasma and the lower limit of quantitation was determined at 20ng/mL with accuracies within ±10% of nominal and precisions less than 12%. Their recoveries ranged from 62 to 96% by using liquid-liquid extraction. With an improved assay sensitivity compared to analogues, the derivative 4-OHIFO-SCZ was stable in plasma at 4°C for 24h and at -20°C for three months. For all compounds, the assay was validated with accuracies within ±13% and precisions less than 15%. This method was applied to a comparative pharmacokinetic study of 4-OHIFO from IFO and three derivatives RXIFO in mice. This active metabolite was produced by some of the novel conjugates with good pharmacokinetic properties. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Impact of Cytochrome P450 2D6 Function on the Chiral Blood Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine (MDMA) and Its Phase I and II Metabolites in Humans.

    Science.gov (United States)

    Steuer, Andrea E; Schmidhauser, Corina; Tingelhoff, Eva H; Schmid, Yasmin; Rickli, Anna; Kraemer, Thomas; Liechti, Matthias E

    2016-01-01

    3,4-methylenedioxymethamphetamine (MDMA; ecstasy) metabolism is known to be stereoselective, with preference for S-stereoisomers. Its major metabolic step involves CYP2D6-catalyzed demethylenation to 3,4-dihydroxymethamphetamine (DHMA), followed by methylation and conjugation. Alterations in CYP2D6 genotype and/or phenotype have been associated with higher toxicity. Therefore, the impact of CYP2D6 function on the plasma pharmacokinetics of MDMA and its phase I and II metabolites was tested by comparing extensive metabolizers (EMs), intermediate metabolizers (IMs), and EMs that were pretreated with bupropion as a metabolic inhibitor in a controlled MDMA administration study. Blood plasma samples were collected from 16 healthy participants (13 EMs and three IMs) up to 24 h after MDMA administration in a double-blind, placebo-controlled, four-period, cross-over design, with subjects receiving 1 week placebo or bupropion pretreatment followed by a single placebo or MDMA (125 mg) dose. Bupropion pretreatment increased the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from 0 to 24 h (AUC24) of R-MDMA (9% and 25%, respectively) and S-MDMA (16% and 38%, respectively). Bupropion reduced the Cmax and AUC24 of the CYP2D6-dependently formed metabolite stereoisomers of DHMA 3-sulfate, DHMA 4-sulfate, and 4-hydroxy-3-methoxymethamphetamine (HMMA sulfate and HMMA glucuronide) by approximately 40%. The changes that were observed in IMs were generally comparable to bupropion-pretreated EMs. Although changes in stereoselectivity based on CYP2D6 activity were observed, these likely have low clinical relevance. Bupropion and hydroxybupropion stereoisomer pharmacokinetics were unaltered by MDMA co-administration. The present data might aid further interpretations of toxicity based on CYP2D6-dependent MDMA metabolism.

  9. Impact of Cytochrome P450 2D6 Function on the Chiral Blood Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine (MDMA and Its Phase I and II Metabolites in Humans.

    Directory of Open Access Journals (Sweden)

    Andrea E Steuer

    Full Text Available 3,4-methylenedioxymethamphetamine (MDMA; ecstasy metabolism is known to be stereoselective, with preference for S-stereoisomers. Its major metabolic step involves CYP2D6-catalyzed demethylenation to 3,4-dihydroxymethamphetamine (DHMA, followed by methylation and conjugation. Alterations in CYP2D6 genotype and/or phenotype have been associated with higher toxicity. Therefore, the impact of CYP2D6 function on the plasma pharmacokinetics of MDMA and its phase I and II metabolites was tested by comparing extensive metabolizers (EMs, intermediate metabolizers (IMs, and EMs that were pretreated with bupropion as a metabolic inhibitor in a controlled MDMA administration study. Blood plasma samples were collected from 16 healthy participants (13 EMs and three IMs up to 24 h after MDMA administration in a double-blind, placebo-controlled, four-period, cross-over design, with subjects receiving 1 week placebo or bupropion pretreatment followed by a single placebo or MDMA (125 mg dose. Bupropion pretreatment increased the maximum plasma concentration (Cmax and area under the plasma concentration-time curve from 0 to 24 h (AUC24 of R-MDMA (9% and 25%, respectively and S-MDMA (16% and 38%, respectively. Bupropion reduced the Cmax and AUC24 of the CYP2D6-dependently formed metabolite stereoisomers of DHMA 3-sulfate, DHMA 4-sulfate, and 4-hydroxy-3-methoxymethamphetamine (HMMA sulfate and HMMA glucuronide by approximately 40%. The changes that were observed in IMs were generally comparable to bupropion-pretreated EMs. Although changes in stereoselectivity based on CYP2D6 activity were observed, these likely have low clinical relevance. Bupropion and hydroxybupropion stereoisomer pharmacokinetics were unaltered by MDMA co-administration. The present data might aid further interpretations of toxicity based on CYP2D6-dependent MDMA metabolism.

  10. Evaluation of deltamethrin kinetics and dosimetry in the maturing rat using a PBPK model

    International Nuclear Information System (INIS)

    Tornero-Velez, Rogelio; Mirfazaelian, Ahmad; Kim, Kyu-Bong; Anand, Sathanandam S.; Kim, Hyo J.; Haines, Wendy T.; Bruckner, James V.; Fisher, Jeffrey W.

    2010-01-01

    Immature rats are more susceptible than adults to the acute neurotoxicity of pyrethroid insecticides like deltamethrin (DLM). A companion kinetics study (Kim et al., in press) revealed that blood and brain levels of the neuroactive parent compound were inversely related to age in rats 10, 21, 40 and 90 days old. The objective of the current study was to modify a physiologically based pharmacokinetic (PBPK) model of DLM disposition in the adult male Sprague-Dawley rat (Mirfazaelian et al., 2006), so blood and target organ dosimetry could be accurately predicted during maturation. Age-specific organ weights and age-dependent changes in the oxidative and hydrolytic clearance of DLM were modeled with a generalized Michaelis-Menten model for growth and the summary equations incorporated into the PBPK model. The model's simulations compared favorably with empirical DLM time-courses in plasma, blood, brain and fat for the four age-groups evaluated (10, 21, 40 and 90 days old). PND 10 pups' area under the 24-h brain concentration time curve (AUC 0-24h ) was 3.8-fold higher than that of the PND 90 adults. Our maturing rat PBPK model allows for updating with age- and chemical-dependent parameters, so pyrethroid dosimetry can be forecast in young and aged individuals. Hence, this model provides a methodology for risk assessors to consider age-specific adjustments to oral Reference Doses on the basis of PK differences.

  11. Chemical dosimetry principles in high dose dosimetry

    International Nuclear Information System (INIS)

    Mhatre, Sachin G.V.

    2016-01-01

    In radiation processing, activities of principal concern are process validation and process control. The objective of such formalized procedures is to establish documentary evidence that the irradiation process has achieved the desired results. The key element of such activities is inevitably a well characterized reliable dosimetry system that is traceable to recognized national and international dosimetry standards. Only such dosimetry systems can help establish the required documentary evidence. In addition, industrial radiation processing such as irradiation of foodstuffs and sterilization of health careproducts are both highly regulated, in particular with regard to dose. Besides, dosimetry is necessary for scaling up processes from the research level to the industrial level. Thus, accurate dosimetry is indispensable

  12. Dosimetry system 1986

    International Nuclear Information System (INIS)

    Woolson, William A.; Egbert, Stephen D.; Gritzner, Michael L.

    1987-01-01

    In May 1983, the authors proposed a dosimetry system for use by the Radiation Effects Research Foundation (RERF) that would incorporate the new findings and calculations of the joint United States - Japan working groups on the reassessment of A-bomb dosimetry. The proposed dosimetry system evolved from extensive discussions with RERF personnel, numerous meetings of the scientists from Japan and the United States involved in the dosimetry reassessment research, and requirements expressed by epidemiologists and radiobiologists on the various review panels. The dosimetry system proposed was based on considerations of the dosimetry requirements for the normal work of RERF and for future research in radiobiology, the computerized input data on A-bomb survivors available in the RERF data base, the level of detail, precision, and accuracy of various components of the dosimetric estimates, and the computer resources available at RERF in Hiroshima. These discussions and our own experience indicated that, in light of the expansion of computer and radiation technologies and the desire for more detail in the dosimetry, an entirely new approach to the dosimetry system was appropriate. This resulted in a complete replacement of the T65D system as distinguished from a simpler approach involving a renormalization of T65D parameters to reflect the new dosimetry. The proposed dosimetry system for RERF and the plan for implementation was accepted by the Department of Energy (DOE) Working Group on A-bomb Dosimetry chaired by Dr. R.F. Christy. The dosimetry system plan was also presented to the binational A-bomb dosimetry review groups for critical comment and was discussed at joint US-Japan workshop. A prototype dosimetry system incorporating preliminary dosimetry estimates and applicable to only a limited set of A-bomb survivors was installed on the RERF computer system in the fall of 1984. This system was successfully operated at RERF and provided an initial look at the impact of

  13. Applications of gel dosimetry

    International Nuclear Information System (INIS)

    Ibbott, Geoffrey S

    2004-01-01

    Gel dosimetry has been examined as a clinical dosimeter since the 1950s. During the last two decades, however, a rapid increase in the number of investigators has been seen, and the body of knowledge regarding gel dosimetry has expanded considerably. Gel dosimetry is still considered a research project, and the introduction of this tool into clinical use is proceeding slowly. This paper will review the characteristics of gel dosimetry that make it desirable for clinical use, the postulated and demonstrated applications of gel dosimetry, and some complications, set-backs, and failures that have contributed to the slow introduction into routine clinical use

  14. Development of an ultra-fast liquid chromatography-tandem mass spectrometry method for simultaneous determination of seven flavonoids in rat plasma: Application to a comparative pharmacokinetic investigation of Ginkgo biloba extract and single pure ginkgo flavonoids after oral administration.

    Science.gov (United States)

    Wang, Tianyang; Xiao, Jie; Hou, Huiping; Li, Pei; Yuan, Ziyue; Xu, Huarong; Liu, Ran; Li, Qing; Bi, Kaishun

    2017-08-15

    For deeper pharmacokinetic investigation and further curative application of ginkgo flavonoids, a delicate, efficient and precise UFLC-MS/MS technique for synchronous quantitation of seven flavonoids, apigenin, luteolin, naringenin, quercetin, diosmetin, kaempferol and isorhamnetin in rat plasma has been established. After mixing with the internal standard (IS) linarin, bio-samples were pretreated via ethyl acetate for liquid-liquid extraction, then isolated at 0.2ml/min flow rate on a Venusil MP C 18 chromatographic column (100mm×2.1mm, 3μm) by means of gradient elution. 0.1% formic acid-water and methanol system was used as the mobile phase. Mass spectrometric inspection was conducted on a 4000Q UFLC-MS/MS system with turbo ion spray source in patterns of negative ion and multiple reaction-monitoring (MRM). All calibration curves proved favorable linearity (R 2 ≥0.9918) in linear ranges. Intra-day and inter-day precisions didn't exceed 14.0% for all the analytes, and the accuracy was within 6.9%. Extraction recoveries of analytes and IS were less than ±15.0% of nominal concentrations. This method has been under thorough and firm verification for a comparative pharmacokinetic research after gavage between Ginkgo biloba extract and single pure ginkgo flavonoids. The results demonstrated that there're evident pharmacokinetic discrepancies, and possible structural influences were innovatively proposed. Generally, substitution with 3-hydroxylation, a double bond in ring C, ring B methoxylation often confer longer onset period. The existence of ring B catechol group gives rise to faster clearance. Copyright © 2017. Published by Elsevier B.V.

  15. A comparative pharmacokinetic study of three flavonoids and three anthraquinones in normal and gastrointestinal motility disorders rat plasma after the oral administration of Wei-Chang-Shu tablet using high-performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Ren, Yan; Zhao, Weiwei; Zhao, Juanjuan; Chen, Xiangming; Yu, Chen; Liu, Mengan

    2017-11-01

    A simple, fast and reliable high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification and pharmacokinetic study of three flavonoids (liquiritigenin, isoliquiritigenin and formononetin) and three anthraquinones (emodin, rhein and aloe-emodin), which are the bioactive ingredients of Wei-Chang-Shu tablet found in rat plasma. After extraction by liquid-liquid extraction with ethyl acetate, chromatographic separation was achieved on an Agilent Zorbax SB-C 18 column (4.6 × 150 mm, 5 μm) at a flow rate of 1 mL/min by gradient elution using 0.1% aqueous acetic acid and acetonitrile. The detection was performed using a triple quadrupole mass spectrometer equipped with electrospray ionization source in the negative ionization and selected reaction monitoring mode. Method validation was performed in terms of specificity, carryover, linearity (r > 0.99), intra-/inter-day precision (1.0-10.1%), accuracy (relative error, <7.6%), stability (0.6-13.2%), extract recovery (74.9-91.9%) and matrix effect (89.1-109%). The lower limits of quantification of the six analytes varied from 0.92 to 10.4 ng/mL. The validated method was successfully applied to compare the pharmacokinetic properties of Wei-Chang-Shu tablet in normal rats and in rats with gastrointestinal motility disorders. The results indicated that there were obvious differences in the pharmacokinetic behavior between normal and model rats. This study will be helpful in the clinical application of Wei-Chang-Shu tablet. Copyright © 2017 John Wiley & Sons, Ltd.

  16. Simultaneous Determination of Purpurin, Munjistin and Mollugin in Rat Plasma by Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry: Application to a Pharmacokinetic Study after Oral Administration of Rubia cordifolia L. Extract

    Directory of Open Access Journals (Sweden)

    Mingjie Gao

    2016-06-01

    Full Text Available A specific, simple, sensitive Ultra High Performance Liquid Chromatography-tandem Mass Spectrometry (UHPLC-MS/MS method has been developed and validated for the simultaneous determination and pharmacokinetic study of purpurin, munjistin, and mollugin in rat plasma. Chromatographic separation was carried out using a C18 column (ACQUITY UPLC® HSS T3, 1.8 μm, 2.1 × 100 mm with gradient elution. The compounds were detected on a 6430 triple-quadrupole tandem MS with an electrospray ionization (ESI interface using multiple reaction monitoring (MRM in positive ionization mode. The samples were prepared by a liquid-liquid extraction (LLE method with ethyl acetate after being spiked with an internal standard (bifendate. The current UHPLC-MS/MS assay was validated for its linearity, intra-day and inter-day precisions, accuracy, extraction recovery, matrix effect and stability in different conditions. The method was linear for all analytes over the investigated range with all determined correlation coefficients exceeding 0.9900. The intra-day and inter-day precisions were in the range of 4.21% to 14.84%, and the relative errors of accuracies were in the range of −14.05% to 14.75%. The mean recoveries and matrix effects of purpurin, munjistin, and mollugin were higher than 78.87% and 92.56%, repectively. After oral administration of 0.82 g/kg of Rubia cordifolia extract, the maximum plasma concentrations (Cmax were 70.10 ± 11.78 ng/mL for purpurin, 26.09 ± 6.6 ng/mL for munjistin, and 52.10 ± 6.71 ng/mL for mollugin. The time for maximal concentration (Tmax was 1.61 ± 0.24 h for purpurin, 2.58 ± 0.19 h for munjistin, and 1.99 ± 0.21 h for mollugin. The established method was further applied to a pharmacokinetic study of purpurin, munjistin, and mollugin in rat plasma. It was concluded from the pharmacokinetic parameters that the three analytes showed a process of slow absorption and metabolism after oral administration of R. cordifolia extract to

  17. An ultra high performance liquid chromatography with tandem mass spectrometry method for plasma and cerebrospinal fluid pharmacokinetics of rhein in patients with traumatic brain injury after administration of rhubarb decoction.

    Science.gov (United States)

    Wang, Yang; Fan, Rong; Luo, Jiekun; Tang, Tao; Xing, Zhihua; Xia, Zian; Peng, Weijun; Wang, Wenzhu; Lv, Huiying; Huang, Wei; Liang, Yizeng; Yi, Lunzhao; Lu, Hongmei; Huang, Xi

    2015-04-01

    Damage of blood-brain barrier is a common result of traumatic brain injury. This damage can open the blood-brain barrier and allow drug passage. An ultraperformance liquid chromatography with tandem mass spectrometry method was established to determine the concentration of rhein in the biofluids (plasma and cerebrospinal fluid) of patients with a compromised blood-brain barrier following traumatic brain injury after rhubarb administration. Furthermore, the pharmacokinetic profiles were analyzed. A triple-quadruple tandem mass spectrometer with electrospray ionization was used for rhein detection. The mass transition followed was m/z 283.06→239.0. The calibration curve was linear in the concentration range of 10-8000 ng/mL for the biofluids. The intra- and interday precisions were less than 10%. The relative standard deviation of recovery was less than 15% in biological matrices. The pharmacokinetic data showed that rhein was rapidly transported into biofluids, and exhibited a peak concentration 1 h after rhubarb administration. The elimination rate of rhein was slow. The AUCcerebrospinal fluid /AUCplasma (AUC is area under curve) of rhein was approximately 17%, indicating that portions of rhein could pass the impaired blood-brain barrier. The method was successfully applied to quantify rhein in the biofluids of all patients. The data presented can help to guide clinical applications of rhubarb for treating traumatic brain injury. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Quantification of nimesulide in human plasma by high-performance liquid chromatography with ultraviolet detector (HPLC-UV): application to pharmacokinetic studies in 28 healthy Korean subjects.

    Science.gov (United States)

    Kim, Mi-Sun; Park, Yoo-Sin; Kim, Shin-Hee; Kim, Sang-Yeon; Lee, Min-Ho; Kim, Youn-Hee; Kim, Do-Wan; Yang, Seok-Chul; Kang, Ju-Seop

    2012-05-01

    Nimesulide is a selective COX-2 inhibitor that is as effective as the classical non-acidic nonsteroidal anti-inflammatory drugs in the relief of various pain and inflammatory conditions, but is better tolerated with lower incidences of adverse effects than other drugs. After oral dose of 100 mg nimesulide to western subjects, a mean maximal concentration (C(max)) of 2.86 ∼ 6.5 µg/mL was reached at 1.22 ∼ 2.75 h and mean t(1/2β) of 1.8 ∼ 4.74 h. This study developed a robust method for quantification of nimesulide for the pharmacokinetics and suitability of its dosage in Korea and compared its suitability with other racial populations. Nimesulide and internal standard were extracted from acidified samples with methyl tert-butyl ether and analyzed by high-performance liquid chromatography with ultraviolet detection (HPLC-UV). The 28 healthy volunteers took 2 tablets of 100 mg nimesulide and blood concentrations were analyzed during the 24 h post dose. Several pharmacokinetic parameters were represented: AUC(0-infinity) = 113.0 mg-h/mL, C(max) = 12.06 mg/mL, time for maximal concentrations (T(max)) = 3.19 h and t(1/2β) = 4.51 h. These were different from those of western populations as follows: AUC was 14.5% and C(max) was 28% that of of Korean subjects and T(max) and t(1/2β) were also different. The validated HPLC-UV method was successfully applied for the pharmacokinetic studies of nimesulide in Korean subjects. Because the pharmacokinetics of nimesulide were different from western populations, its dosage regimen needs to be adjusted for Koreans. © The Author [2012]. Published by Oxford University Press. All rights reserved.

  19. Thermoluminescence albedo-neutron dosimetry

    International Nuclear Information System (INIS)

    Strand, T.; Storruste, A.

    1986-10-01

    The report discusses neutron detection with respect to dosimetry and compares different thermoluminescent dosimetry materials for neutron dosimetry. Construction and calibration of a thermoluminescence albedo neutron dosemeter, developed by the authors, is described

  20. Thermoluminescence in medical dosimetry

    International Nuclear Information System (INIS)

    Rivera, T.

    2011-10-01

    The dosimetry by thermoluminescence (Tl) is applied in the entire world for the dosimetry of ionizing radiations specially to personal and medical dosimetry. This dosimetry method has been very interesting for measures in vivo because the Tl dosimeters have the advantage of being very sensitive in a very small volume and they are also equivalent to tissue and they do not need additional accessories (for example, cable, electrometer, etc.) The main characteristics of the diverse Tl materials to be used in the radiation measures and practical applications are: the Tl curve, the share homogeneity, the signal stability after the irradiation, precision and exactitude, the response in function with the dose and the energy influence. In this work a brief summary of the advances of the radiations dosimetry is presented by means of the thermally stimulated luminescence and its application to the dosimetry in radiotherapy. (Author)

  1. Simultaneous quantification of chrysophanol and physcion in rat plasma by ultra fast liquid chromatography-tandem mass spectrometry and application of the technique to comparative pharmacokinetic studies of Radix et Rhei Rhizoma extract alone and Dahuang Fuzi Decoction.

    Science.gov (United States)

    Liu, Xiao; Li, Huan; Wu, Li; Xing, Jiangwa; Poh, Yanhong; Cai, Hao; Cai, Bao Chang

    2015-02-01

    Most herbal medicines are prescribed in combination based on the theory of TCM to obtain synergistic effects or diminish the possible adverse reactions. Compatibility refers to the combination of two or more herbs based on the clinical settings and the properties of herbs. Chrysophanol and physcion are the main effective compounds in Radix et Rhizoma Rhei and Dahuang Fuzi Decoction which is the combination of Radix et Rhizoma Rhei, Radix Aconiti Lateralis Praeparata and Radix et Rhizoma Asari. However, chrysophanol and physcion are difficult to detect in vivo because of their low concentration and interference from endogenous compounds. The aim of this study is to develop a rapid, specific and sensitive ultra high performance liquid chromatography-triple quadrupole tandem mass method to simultaneously quantify chrysophanol and physcion in rat plasma, in order to better understand the pharmacokinetics and compatibility mechanism of Dahuang Fuzi Decoction for the first time. Multiple reaction monitoring (MRM) mode was applied for the quantitation at [M-H](-)m/z 253.0→m/z 225.1 for chrysophanol, [M-H](-) for m/z 283.1→m/z 240.0 physcion and [M-H](-)m/z 239.0→m/z 211.0 for IS. The analytes were separated on an Agilent Eclipse plus C18 column (100mm×2.1mm, 1.8μm) column within a total running time of 6.5min using a mixture of 3mM ammonium acetate in water and methanol (95:5, v/v) with a time program flow gradient according to the "plus gradient chromatography" theory. The inclusion of the ammonium acetate in the UFLC mobile phase dramatically improved the detection limit of the tested compounds and decreased the interference by matrix effects, which have been referred to as "LC-electrolyte effects". Finally, we demonstrated the application of a validated method in a comparative pharmacokinetic study of rats receiving an oral dose of Dahuang Fuzi Decoction or Radix et Rhei Rhizoma, the monarch drug in the prescription. Pharmacokinetic parameters showed

  2. Thin film tritium dosimetry

    Science.gov (United States)

    Moran, Paul R.

    1976-01-01

    The present invention provides a method for tritium dosimetry. A dosimeter comprising a thin film of a material having relatively sensitive RITAC-RITAP dosimetry properties is exposed to radiation from tritium, and after the dosimeter has been removed from the source of the radiation, the low energy electron dose deposited in the thin film is determined by radiation-induced, thermally-activated polarization dosimetry techniques.

  3. Internal sources dosimetry

    International Nuclear Information System (INIS)

    Savio, Eduardo

    1994-01-01

    The absorbed dose, need of estimation in risk evaluation in the application of radiopharmaceuticals in Nuclear Medicine practice,internal dosimetry,internal and external sources. Calculation methodology,Marinelli model,MIRD system for absorbed dose calculation based on biological parameters of radiopharmaceutical in human body or individual,energy of emitted radiations by administered radionuclide, fraction of emitted energy that is absorbed by target body.Limitation of the MIRD calculation model. A explanation of Marinelli method of dosimetry calculation,β dosimetry. Y dosimetry, effective dose, calculation in organs and tissues, examples. Bibliography .

  4. Dosimetry of ionizing radiation

    International Nuclear Information System (INIS)

    Musilek, L.; Seda, J.; Trousil, J.

    1992-01-01

    The publication deals with a major field of ionizing radiation dosimetry, viz., integrating dosimetric methods, which are the basic means of operative dose determination. It is divided into the following sections: physical and chemical effects of ionizing radiation; integrating dosimetric methods for low radiation doses (film dosimetry, nuclear emulsions, thermoluminescence, radiophotoluminescence, solid-state track detectors, integrating ionization dosemeters); dosimetry of high ionizing radiation doses (chemical dosimetric methods, dosemeters based on the coloring effect, activation detectors); additional methods applicable to integrating dosimetry (exoelectron emission, electron spin resonance, lyoluminescence, etc.); and calibration techniques for dosimetric instrumentation. (Z.S.). 422 refs

  5. Development and validation of a rapid and high-sensitivity liquid chromatography-tandem mass spectrometry assay for the determination of neostigmine in small-volume beagle dog plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Cao, Di; Li, Wenxue; Zhao, Xin; Ye, Xiaolan; Sun, Fanlu; Li, Jinying; Song, Fenyun; Fan, Guorong

    2014-03-01

    A simple, rapid and high sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of neostigmine in small-volume beagle dog plasma was developed to assess the plasma pharmacokinetics of neostigmine. After protein precipitation in a Sirocco 96-well filtration plate, the filtrate was directly injected into the LC-MS/MS system. The analytes were separated on a Hanbon Hedera CN column (100 × 4.6 mm, 5 µm) with a mobile phase composed of methanol-water (60:40, v/v) and the water containing 0.01% formic acid at a flow rate of 0.6mL/min, with a split ratio of 1:1 flowing 300 μL into the mass spectrometer. The run time was 3 min. Detection was accomplished by electrospray ionization source in multiple reactions monitoring mode with the precursor-to-product ion transitions m/z 223.0 → 72.0 and 306.0 → 140.0 for neostigmine and anisodamine (internal standard), respectively. The method was sensitive with a lower limit of quantitation of 0.1 ng/mL, and good linearity in the range 0.1-100ng/mL for neostigmine (r ≥ 0.998). All the validation data, such as accuracy, intra-run and inter-run precision, were within the required limits. The method was successfully applied to pharmacokinetic study of neostigmine methylsulfate injection in beagle dogs. Copyright © 2013 John Wiley & Sons, Ltd.

  6. A novel LC-MS/MS assay for the simultaneous determination of melatonin and its two major metabolites, 6-hydroxymelatonin and 6-sulfatoxymelatonin in dog plasma: Application to a pharmacokinetic study.

    Science.gov (United States)

    Zhao, Huimin; Wang, Yifei; Yuan, Bo; Liu, Shu; Man, Shuang; Xu, Haiyan; Lu, Xiumei

    2016-01-05

    A convenient and specific liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of melatonin (MEL) and its major metabolites, 6-hydroxymelatonin (6-O-MEL) and 6-sulfatoxymelationin (S-O-MEL) in dog plasma. After plasma samples were deproteinized with acetonitrile, the post-treatment samples were analyzed on a Phenomenex Kinetex C18 column (50×2.1 mm, 1.7 μm) interfaced with a triple quadrupole tandem mass spectrometer. Electrospray ionization mode (ESI) and multiple reaction monitoring were used to assay MEL and its metabolites. Acetonitrile and 5 mM ammonium acetate were used as the mobile phase with a gradient elution at a flow rate of 0.2 mL/min. The analytical run time of 6.5 min was divided into two periods according to ionization mode. S-O-MEL was monitored in negative ionization mode (period 1), while MEL and 6-O-MEL were detected in positive ionization mode (period 2). All calibration curves showed good linearity (r>0.991) over the concentration range with a lower limit of quantification (LLOQ) of 0.02 ng/mL for MEL, 0.04 ng/mL for 6-O-MEL and 0.50 ng/mL for S-O-MEL. The intra- and inter-day precision was within 13.5% in terms of relative standard deviation (RSD%) and the accuracy within 13.0% in terms of relative error. This convenient and specific LC-MS/MS method was successfully applied to the pharmacokinetic study of MEL and its metabolites in Beagle dogs after an oral dose of 2.0mg MEL. After ingestion of MEL, S-O-MEL was the predominant component circulating in blood. 6-O-MEL showed similar pharmacokinetic profile to that of MEL. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Simultaneous Determination of Bergapten, Imperatorin, Notopterol, and Isoimperatorin in Rat Plasma by High Performance Liquid Chromatography with Fluorescence Detection and Its Application to Pharmacokinetic and Excretion Study after Oral Administration of Notopterygium incisum Extract

    Directory of Open Access Journals (Sweden)

    John Teye Azietaku

    2016-01-01

    Full Text Available A specific, sensitive, and reliable high performance liquid chromatography with fluorescence detection (HPLC-FLD was first optimized and then used in the simultaneous quantification of bergapten, imperatorin, notopterol, and isoimperatorin in rat plasma using osthole as the internal standard. Liquid-liquid extraction with ethyl acetate was employed in treating the rat plasma samples obtained. Separation was carried out with a Hedera™ ODS column (4.6 × 250 mm, 5 μm by gradient elution at a temperature of 40°C. Excitation and emission of the fluorescence detector were set to 300 and 490 nm, respectively. The lower limits of quantification for bergapten, imperatorin, notopterol, and isoimperatorin in rat plasma were 4, 40, 4, and 2 ng mL−1, respectively. The intraday and interday precision and accuracy for the four coumarins were within acceptable criteria. The recovery of the method was satisfactory with a range of 80.3–114%. The validated method was successfully used for the simultaneous determination of the four coumarins in Notopterygium incisum extracts and also for the pharmacokinetic and excretion study of bergapten, imperatorin, notopterol, and isoimperatorin in rats.

  8. Development and validation of a sensitive liquid chromatographic-tandem mass spectrometric method for the simultaneous analysis of granisetron and 7-hydroxy granisetron in human plasma and urine samples: application in a clinical pharmacokinetic study in pregnant subject.

    Science.gov (United States)

    Zhao, Yang; Chen, Hui-Jun; Caritis, Steve; Venkataramanan, Raman

    2016-02-01

    A liquid chromatography-tandem mass spectrometric method for the quantification of granisetron and its major metabolite, 7-hydroxy granisetron in human plasma and urine samples was developed and validated. Respective stable isotopically labeled granisetron and 7-hydroxy granisetron were used as internal standards (IS). Chromatography was performed using an Xselect HSS T3 analytical column with a mobile phase of 20% acetonitrile in water (containing 0.2 mM ammonium formate and 0.14% formic acid, pH 4) delivered in an isocratic mode. Tandem mass spectrometry operating in positive electrospray ionization mode with multiple reaction monitoring was used for quantification. The standard curves were linear in the concentration ranges of 0.5-100 ng/mL for granisetron and 0.1-100 ng/mL for 7-hydroxy granisetron in human plasma samples, and 2-2000 ng/mL for granisetron and 2-1000 ng/mL for 7-hydroxy granisetron in human urine samples, respectively. The accuracies were >85% and the precision as determined by the coefficient of variations was granisetron or 7-hydroxy granisetron in either plasma or urine samples. Granisetron was stable under various storage and experimental conditions. This validated method was successfully applied to a pharmacokinetic study after intravenous administration of 1 mg granisetron to a pregnant subject. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Determination of piperphentonamine and metabolites M1 and M6 in human plasma and urine by LC/MS/MS and its application in a pharmacokinetics study in Chinese healthy volunteers.

    Science.gov (United States)

    Shi, Aixin; Hu, Xin; Li, Kexin; Li, Jian; Han, Liping; Wan, Huayin; Li, Rubing

    2012-11-01

    Piperphentonamine hydrochloride (PPTA) is a new calcium sensitizer. A liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for determination of piperphentonamine and its metabolites M1 and M6 was developed for the first time and applied to a pharmacokinetics study. Protein precipitation was used for pre-treatment of plasma samples, and solid phase extraction method was used for pre-treatment of urine samples. The chromatographic separation was achieved on a C(18) column using gradient elution in this study: A: 1% acetic acid aqueous solution, and B: acetonitrile. The whole analysis lasted for 10.5min and the gradient flow rate was 0.25mL/min constantly. The detection was performed of a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via a positive electrospray ionization source. The results were that the m/z ratios of monitored precursor ions and product ions of PPTA, M1 and M6 were 354.0→191.8, 356.0→148.7 and 358.0→148.7, respectively. From the standard curve, the concentration ranges of both PPTA and M1 in blood and urine samples were 0.1-500ng/mL and 0.1-200ng/mL, respectively; the concentration ranges of M6 in blood sample and urine sample were 0.2-500ng/mL and 0.2-200ng/mL, respectively; and the correlation coefficient of standard curve was r>0.99. A total of 31 healthy Chinese subjects participated in the pharmacokinetic study of single bolus intravenous injection of piperphentonamine hydrochloride. They were divided into three dosage groups and given 0.2, 0.4 and 0.6mg/kg of PPTA. After drug administration, concentrations of PPTA, M1 and M6 in human plasma and urine samples were determined to evaluation the pharmacokinetic characteristics of PPTA and its metabolites M1 and M6. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Effect of Dehydration on the Pharmacokinetics of Mefenamic Acid

    OpenAIRE

    QAMAR, Shadab

    2014-01-01

    The pharmacokinetic properties and bioavailability of mefenamic acid was studied in normal and dehydrated rabbits. High perfomance liquid chromatography (HPLC) was used for the assay of mefenamic acid in plasma samples. The mean plasma concentration and area under the plasma concentration-time curve decreased but the volume of distribution and total body clearance increased significantly (P

  11. Sensitive LC-MS/MS Method for the Simultaneous Determination of Bendamustine and its Active Metabolite, γ-Hydroxybendamustine in Small Volume Mice and Dog Plasma and its Application to a Pharmacokinetic Study in Mice and Dogs.

    Science.gov (United States)

    Chandrashekar, Devaraj V; Suresh, Ponnayyan S; Kumar, Rajnish; Bhamidipati, Ravi Kanth; Mullangi, Ramesh; Richter, Wolfgang; Srinivas, Nuggehally R

    2017-09-01

    A highly sensitive, specific and rapid LC-ESI-MS/MS method has been developed and validated for the simultaneous quantification of bendamustine (BM) and γ-hydroxybendamustine (HBM) in small volume (20 µL) mice and dog plasma using phenacetin as an internal standard (IS) as per regulatory guidelines. Both the analytes and IS were extracted from mice and dog plasma using a liquid-liquid extraction method. Chromatography was achieved on Atlantis dC 18 column using an isocratic mobile phase (0.2% formic acid:acetonitrile, 25:75) at a flow rate of 0.40 mL/min. The total chromatographic run time was 3.0 min and the elution of BM, HBM and IS occurred at ~1.2, 1.2 and 2.0 min, respectively. A linear response function was established 0.11-518 ng/mL for both the analytes in mice and dog plasma. The intra- and inter-day accuracy and precisions were in the range of 3.46-12.9 and 3.63-8.23%; 1.15-9.00 and 7.86-9.49% for BM and HBM, respectively in mice plasma and 2.15-6.49 and 1.73-13.1%; 4.35-13.9 and 4.33-10.5% for BM and HBM, respectively in dog plasma. This novel method has been applied to a pharmacokinetic study in mice and dogs. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Radiochromic film dosimetry

    International Nuclear Information System (INIS)

    Xu Zhiyong

    2002-01-01

    Radiochromic film dosimetry was developed to measure ionization irradiation dose for industry and medicine. At this time, there are no comprehensive guideline on the medical application, calibration method and densitometer system for medicine. The review gives update on Radiochromic film dosimetry used for medicine, including principles, film model and material, characteristics, calibration method, scanning densitometer system and medical application

  13. Nuclear accident dosimetry

    International Nuclear Information System (INIS)

    1982-01-01

    The film presents statistical data on criticality accidents. It outlines past IAEA activities on criticality accident dosimetry and the technical documents that resulted from this work. The film furthermore illustrates an international comparison study on nuclear accident dosimetry conducted at the Atomic Energy Research Establishment, Harwell, United Kingdom

  14. Personal dosimetry in Kazakhstan

    International Nuclear Information System (INIS)

    Khvoshnyanskaya, I.R.; Vdovichenko, V.G.; Lozbin, A.Yu.

    2003-01-01

    KATEP-AE Radiation Laboratory is the first organization in Kazakhstan officially licensed by the Kazakhstan Atomic Energy Committee to provide individual dosimetry services. The Laboratory was established according to the international standards. Nowadays it is the largest company providing personal dosimetry services in the Republic of Kazakhstan. (author)

  15. Nuclear accident dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1983-12-31

    The film presents statistical data on criticality accidents. It outlines past IAEA activities on criticality accident dosimetry and the technical documents that resulted from this work. The film furthermore illustrates an international comparison study on nuclear accident dosimetry conducted at the Atomic Energy Research Establishment, Harwell, United Kingdom

  16. Pharmacokinetics of Botanical Drugs and Plant Extracts.

    Science.gov (United States)

    Dominguez More, Gina Paola; Cardenas, Paola Andrea; Costa, Geison M; Simoes, Claudia M O; Aragon, Diana Marcela

    2017-01-01

    Botanical drugs contain plant extracts, which are complex mixtures of compounds. As with conventional drugs, it is necessary to validate their efficacy and safety through preclinical and clinical studies. However, pharmacokinetic studies for active constituents or characteristic markers in botanical drugs are rare. The objective of this review was to investigate the global state of the art in pharmacokinetic studies of active ingredients present in plant extracts and botanical drugs. A review of pharmacokinetics studies of chemical constituents of plant extracts and botanical drugs was performed, with a total of 135 studies published between January 2004 and February 2015 available in recognized scientific databases. Botanical preparations were mainly found in the form of aqueous extracts of roots and rhizomes. The most widely studied species was Salvia miltiorrhiza Bunge, and the compound most frequently used as a pharmacokinetic marker was berberine. Most studies were performed using the Sprague Dawley rat model, and the preparations were mainly administered orally in a single dose. Quantification of plasma concentrations of pharmacokinetic markers was performed mainly by liquid-liquid extraction, followed by high performance liquid chromatography coupled to mass spectrometry detector. In conclusion, in recent years there has been an increasing interest among researchers worldwide in the study of pharmacokinetics of bioactive compounds in botanical drugs and plant extracts, especially those from the Traditional Chinese Medicine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. 100 years of solid state dosimetry and radiation protection dosimetry

    International Nuclear Information System (INIS)

    Bartlett, David T.

    2008-01-01

    The use of solid state detectors in radiation dosimetry has passed its 100th anniversary. The major applications of these detectors in radiation dosimetry have been in personal dosimetry, retrospective dosimetry, dating, medical dosimetry, the characterization of radiation fields, and also in microdosimetry and radiobiology research. In this introductory paper for the 15th International Conference, I shall speak of the history of solid state dosimetry and of the radiation measurement quantities that developed at the same time, mention some landmark developments in detectors and applications, speak a bit more about dosimetry and measurement quantities, and briefly look at the past and future

  18. Dosimetry for radiation processing

    International Nuclear Information System (INIS)

    McLaughlin, W.L.; Boyd, A.W.; Chadwick, K.H.; McDonald, J.C.; Miller, A.

    1989-01-01

    Radiation processing is a relatively young industry with broad applications and considerable commercial success. Dosimetry provides an independent and effective way of developing and controlling many industrial processes. In the sterilization of medical devices and in food irradiation, where the radiation treatment impacts directly on public health, the measurements of dose provide the official means of regulating and approving its use. In this respect, dosimetry provides the operator with a means of characterizing the facility, of proving that products are treated within acceptable dose limits and of controlling the routine operation. This book presents an up-to-date review of the theory, data and measurement techniques for radiation processing dosimetry in a practical and useful way. It is hoped that this book will lead to improved measurement procedures, more accurate and precise dosimetry and a greater appreciation of the necessity of dosimetry for radiation processing. (author)

  19. R-warfarin clearances from plasma associated with polymorphic cytochrome P450 2C19 and simulated by individual physiologically based pharmacokinetic models for 11 cynomolgus monkeys.

    Science.gov (United States)

    Utoh, Masahiro; Kusama, Takashi; Miura, Tomonori; Mitsui, Marina; Kawano, Mirai; Hirano, Takahiro; Shimizu, Makiko; Uno, Yasuhiro; Yamazaki, Hiroshi

    2018-02-01

    1. Cynomolgus monkey cytochrome P450 2C19 (formerly known as P450 2C75), homologous to human P450 2C19, has been identified as R-warfarin 7-hydroxylase. In this study, simulations of R-warfarin clearance in individual cynomolgus monkeys genotyped for P450 2C19 p.[(Phe100Asn; Ala103Val; Ile112Leu)] were performed using individual simplified physiologically based pharmacokinetic (PBPK) modeling. 2. Pharmacokinetic parameters and absorption rate constants, volumes of the systemic circulation, and hepatic intrinsic clearances for individual PBPK models were estimated for eleven cynomolgus monkeys. 3. One-way ANOVA revealed significant effects of the genotype (p warfarin among the homozygous mutant, heterozygous mutant, and wild-type groups. R-Warfarin clearances in individual cynomolgus monkeys genotyped for P450 2C19 were simulated by simplified PBPK modeling. The modeled hepatic intrinsic clearances were significantly associated with the P450 2C19 genotypes. The liver microsomal elimination rates of R-warfarin for individual animals after in vivo administration showed significant reductions associated with the genotype (p warfarin and related medicines associated with polymorphic P450 2C19 in individual cynomolgus monkeys, thereby facilitating calculation of the fraction of hepatic clearance.

  20. Development and full validation of an UPLC-MS/MS method for the determination of an anti-allergic indolinone derivative in rat plasma, and application to a preliminary pharmacokinetic study.

    Science.gov (United States)

    Oufir, Mouhssin; Sampath, Chethan; Butterweck, Veronika; Hamburger, Matthias

    2012-08-01

    The natural product (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)indolin-2-one (indolinone) was identified some years ago as a nanomolar inhibitor of FcɛRI-receptor dependent mast cell degranulation. To further explore the potential of the compound, we established an UPLC-MS/MS assay for dosage in rat plasma. The method was fully validated according to FDA Guidance for industry. Results of this validation and long term stability study demonstrate that the method in lithium heparinized rat plasma is specific, accurate, precise and capable of producing reliable results according to recommendations of international guidelines. The method was validated with a LLOQ of 30.0 ng/mL and an ULOQ of 3000 ng/mL. The response versus concentration data were fitted with a first order polynomial with 1/X(2) weighting. No matrix effect was observed when using three independent sources of rat plasma. The average extraction recovery was consistent over the investigated range. This validation in rat plasma demonstrated that indolinone was stable for 190 days when stored below -65 °C; for 4 days at 10 °C in the autosampler; for 4h at RT, and during three successive freeze/thaw cycles at -65 °C. Preliminary pharmacokinetic data were obtained in male Sprague-Dawley rats (2 mg/kg BW i.v.). Blood samples taken from 0 to 12 h after injection were collected, and data analyzed with WinNonlin. A short half-life (4.30±0.14 min) and a relatively high clearance (3.83±1.46 L/h/kg) were found. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Quantification of 2'-deoxy-2'-β-fluoro-4'-azidocytidine in rat and dog plasma using liquid chromatography-quadrupole time-of-flight and liquid chromatography-triple quadrupole mass spectrometry: Application to bioavailability and pharmacokinetic studies.

    Science.gov (United States)

    Peng, Youmei; Cheng, Tiefeng; Dong, Lihong; Zhang, Yuhai; Chen, Xiaojing; Jiang, Jinhua; Zhang, Jingmin; Guo, Xiaohe; Guo, Mintong; Chang, Junbiao; Wang, Qingduan

    2014-09-01

    2'-Deoxy-2'-β-fluoro-4'-azidocytidine (FNC) is a novel pyrimidine analog that inhibits not only the replication of the hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV but also the replication of lamivudine-resistant HBV, 4'-azidocytidine or 2'-β-methylcytidine-resistant HCV, and nucleoside reverse-transcriptase inhibitor-resistant HIV variants. The present study was undertaken to evaluate the absolute oral bioavailability of FNC in rats and the pharmacokinetic properties of FNC after intragastric administration of single and multiple doses in rats and dogs. A sensitive high-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (HPLC/Q-TOF MS) method and a reliable high-performance liquid chromatography tandem triple quadrupole mass spectrometry (HPLC/QqQ MS/MS) method were established for the determination of FNC in the rat and dog plasmas, respectively. The sample preparation involved a protein-precipitation method with methanol after the addition of lamivudine as an internal standard. FNC was analyzed by LC using a YMC-Pack Pro C18 column (150mm×4.6mm, 3μm) with methanol (containing 0.3% formic acid): 10mM ammonium acetate (containing 0.3% formic acid, pH 2.8) (35:65, v/v) as the mobile phase. Both mass spectrometers were equipped with an electrospray ionization interface in the positive-ion mode. The linear range was from 2.00 to 2000.00ngmL(-1) in rat plasma and 0.50 to 400.00ngmL(-1) in dog plasma. The intraday and interday precision were less than 10.55%, and the accuracy was in the range of -5.86 to 5.13%. The mean recoveries were greater than 82.70% and 82.97% for FNC and IS, respectively. The HPLC/Q-TOF MS and HPLC/QqQ MS/MS methods were both successfully applied in the pharmacokinetic studies of FNC in rats and dogs. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Simultaneous quantification of reparixin and paclitaxel in plasma and urine using ultra performance liquid chromatography-tandem mass spectroscopy (UHPLC-MS/MS): Application to a preclinical pharmacokinetic study in rats.

    Science.gov (United States)

    Malhi, Sarandeep; Stesco, Nicholas; Alrushaid, Samaa; Lakowski, Ted M; Davies, Neal M; Gu, Xiaochen

    2017-03-01

    A liquid chromatography-tandem mass spectroscopy (LC-MS/MS) assay was developed and validated to simultaneously quantify anticancer drugs reparixin and paclitaxel in this study. The compounds were extracted from plasma and urine samples by protein precipitation with acetone (supplemented with 0.1% formic acid). Chromatographic separation was achieved using a C18 column, and drug molecules were ionized using dual ion source electrospray and atmospheric pressure chemical ionization (DUIS: ESI-APCI). Reparixin and paclitaxel were quantified using negative and positive multiple reaction monitoring (MRM) mode, respectively. Stable isotope palcitaxel-D5 was used as the internal standard (IS). The assay was validated for specificity, recovery, carryover and sample stability under various storage conditions; it was also successfully applied to measure drug concentrations collected from a pharmacokinetic study in rats. The results confirmed that the assay was accurate and simple in quantifying both reparixin and paclitaxel in plasma and urine with minimal sample pretreatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Simultaneous determination of triterpenoid saponins in dog plasma by a validated UPLC-MS/MS and its application to a pharmacokinetic study after administration of total saponin of licorice.

    Science.gov (United States)

    Tao, Weiwei; Duan, Jinao; Guo, Jianming; Li, Jianping; Tang, Yuping; Liu, Pei; Yang, Nianyun

    2013-03-05

    A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry method was developed for simultaneous determination of eight constituents, uralsaponin C, uralsaponin F, 22β-acetoxyl-glycyrrhizin, 24-hydroxy-licorice-saponin E2, licorice-saponin G2, licorice-saponin E2, glycyrrhizin, and licorice-saponin J2, from total saponin of licorice (TSL) in dog plasma. Ardisiacrispin A was used as the internal standard (IS). The separation was performed on Thermo Syncronic C₁₈ column (100 mm × 2.1 mm, 1.7 μm) at a flow rate of 0.4 mL min⁻¹, and acetonitrile/methanol (3:1, v/v)-0.1% formic acid was used as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) via electrospray ionization (ESI) source with negative ionization mode. All calibration curves had good linearity (r>0.991) over the concentration range from 2.03-405 ng mL⁻¹ to 2.63-2625 ng mL⁻¹ for all components. The intra- and inter-day precision was within 15% and the accuracy ranged from -14.08% to 13.8%. The method was successfully applied to pharmacokinetic study of eight triterpenoid saponins in dog plasma after oral administration of TSL. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  4. A Modified Method for Determination of Lumefantrine in Human Plasma by HPLC-UV and Combination of Protein Precipitation and Solid-Phase Extraction: Application to a Pharmacokinetic Study

    Directory of Open Access Journals (Sweden)

    Liusheng Huang

    2010-03-01

    Full Text Available An HPLC-UV method was developed and validated for the determination of lumefantrine in human plasma. Lumefantrine and its internal standard halofantrine were extracted from plasma samples using protein precipitation with acetonitrile (0.2% perchloric acid followed by solid-phase extraction with Hypersep C8 cartridges. Chromatographic separation was performed on a Zorbax SB-CN HPLC column (3.0 × 150 mm, 3.5 μm with water/methanol (0.1% TFA as the mobile phases in a gradient elution mode. Detection was performed using UV/vis detector at λ = 335 nm. The method showed to be linear over a range of 50–10,000 ng/mL with acceptable intra- and inter-day precision and accuracy. The mean recoveries were 88.2% for lumefatrine and 84.5% for the I.S. The internal standard halofantrine is readily available from commercial sources. This method was successfully applied to a pharmacokinetic interaction study between a first-line antimalarial combination (artemether—lumefantrine and antiretroviral therapy.

  5. Simultaneous determination and pharmacokinetics of danshensu, protocatechuic aldehyde, 4-hydroxy-3-methyloxyphenyl lactic acid and protocatechuic acid in human plasma by LC-MS/MS after oral administration of Compound Danshen Dripping Pills.

    Science.gov (United States)

    Li, Wei; Zhou, Hongjie; Chu, Yang; Wang, Xiangyang; Luo, Ruizhi; Yang, Liu; Polachi, Navaneethakrishnan; Li, Xiao; Chen, Min; Huang, Luqi; Yan, Xueying; Guo, Zhixin; Sun, He

    2017-10-25

    Compound Danshen Dripping Pills (CDDP), a herbal patent medicine, is widely used in China for the prevention and treatment of cardiovascular diseases. A simple, sensitive and reliable method for simultaneous determination of danshensu (DSS), protocatechuic aldehyde (PCA), and their related metabolites, 4-hydroxy-3-methyloxyphenyl lactic acid (HMLA) and protocatechuic acid (PAA) in human plasma was developed and validated based on liquid chromatography tandem mass spectrometry (LC-MS/MS). The analytes and internal standard (IS), vanillic acid (VAA), were extracted from plasma with ethyl acetate and separated on a C 18 column by using the mobile phase consisted of methanol-0.1% formic acid via gradient elution. The electrospray ionization (ESI) source was applied and operated under the multiple reaction monitoring (MRM) mode. The linear calibration curves were obtained at the concentration ranges of 0.46-1000ng/mL for DSS and PAA, and 1.38-1000ng/mL for PCA and HMLA, respectively. The inter- and intra-day precisions (RSD%) were less than 13.5%, and the accuracy (±RE%) was within 13.4%. The described method was successfully applied for the clinical pharmacokinetics of CDDP in Chinese healthy volunteers. Copyright © 2017. Published by Elsevier B.V.

  6. Simultaneous quantification of tafetinib (SIM010603), a novel potent inhibitor of receptor tyrosine kinase, and its major metabolite in dog plasma by HPLC-ESI/MS/MS and its application to a pharmacokinetic study.

    Science.gov (United States)

    Shao, Feng; Zhu, Tian; Tang, Feng; Liu, Xin

    2013-01-01

    This study presents a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI/MS/MS) technique for the simultaneous determination of tafetinib (SIM010603) and its main metabolite (M1) in dog plasma by using Prazosin hydrochloric acid as the internal standard (IS). Both compounds were extracted from dog plasma with ethyl acetate and were separated by HPLC on a reversed phase C₁₈ column with a mobile phase of 10 mM ammonium acetate buffer containing 0.1% formic acid-acetonitrile (40:60, v/v) at a flow rate of 0.2 mL/min. For quantification, the triple-quadruple MS was used in selected reaction monitoring (SRM) mode. The monitored transitions were m/z 425.3 → 309.2 for tafetinib, m/z 397.2 → 309.2 for M1 and m/z 384.2 → 247.1 for IS. The developed method had a short run time of 4 min and good linearity was observed over a wide range of 1-1000 ng/mL for the two compounds. The method was successfully applied in the pharmacokinetic study of tafetinib and M1 in dog. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Simultaneous determination of 3,3',4',5,7-pentamethylquercetin and its possible metabolite 3,3',4',7-tetramethylquercetin in dog plasma by liquid chromatography-tandem mass spectrometry and its application to preclinical pharmacokinetic study.

    Science.gov (United States)

    Chen, Xiaomei; Li, Dongyan; Hu, Yan; Jin, Manwen; Zhou, Liping; Peng, Kelong; Zheng, Heng

    2011-08-01

    A sensitive, simple and rapid ultra fast liquid chromatography (UFLC)-ESI-MS/MS method was established for the simultaneous determination of 3,3',4',5,7-pentamethylquercetin (PMQ) and its possible metabolite 3,3',4',7-tetramethylquercetin (TMQ) in dog plasma using 4',5,7-trimethylapigenin (TMA) as the internal standard. The plasma sample was pretreated with acetonitrile for protein precipitation and the analytes were separated on an Ultimate XB-CN column (5 μm, 2.1 mm × 150 mm) with the mobile phase consisting of acetonitrile and water (2:1, v/v). Detection was performed on a triple-quadrupole tandem mass spectrometer under a positive multiple reaction-monitoring mode (MRM). The mass transition ion-pair was followed as m/z 373.1-312.1 for PMQ, 359.1-344.0 for TMQ and 313.1-298.1 for TMA. The validated concentration ranged from 1.272 to 3060 ng/mL for PMQ and from 10.35 to 1725 ng/mL for TMQ. The lower limit of quantifications for PMQ and TMQ were 1.272 ng/mL and 10.35 ng/mL, respectively. The developed-method was successfully applied for the pharmacokinetic study of PMQ and its metabolite TMQ in dogs following a single oral dose. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Lithium adduct as precursor ion for sensitive and rapid quantification of 20 (S)-protopanaxadiol in rat plasma by liquid chromatography/quadrupole linear ion trap mass spectrometry and application to rat pharmacokinetic study.

    Science.gov (United States)

    Bao, Yuanwu; Wang, Quanying; Tang, Pingming

    2013-03-01

    A novel, rapid and sensitive liquid chromatography/quadrupole linear ion trap mass spectrometry [LC-ESI-(QqLIT)MS/MS] method was developed and validated for the quantification of protopanaxadiol (PPD) in rat plasma. Oleanolic acid (OA) was used as internal standard (IS). A simple protein precipitation based on acetonitrile (ACN) was employed. Chromatographic separation was performed on a Sepax GP-C18 column (50 × 2.1 mm, 5 μM) with a mobile phase consisting of ACN-water and 1.5 μM formic acid and 25 mM lithium acetate (90 : 10, v/v) at a flow rate of 0.4 ml/min for 3.0 min. Multiple-reaction-monitoring mode was performed using lithium adduct ion as precursor ion of m/z 467.5/449.4 and 455.6/407.4 for the drug and IS, respectively. Calibration curve was recovered over a concentration range of 0.5-100 ng/ml with a correlation coefficient >0.99. The limit of detection was 0.2 ng/ml in rat plasma for PPD. The results of the intraday and interday precision and accuracy studies were well within the acceptable limits. The validated method was successfully applied to investigate the pharmacokinetic study of PPD after intravenous and gavage administration to rat. Copyright © 2013 John Wiley & Sons, Ltd.

  9. Simultaneous determination of triamcinolone acetonide palmitate and triamcinolone acetonide in beagle dog plasma by UPLC-MS/MS and its application to a long-term pharmacokinetic study of triamcinolone acetonide palmitate lipid emulsion injection.

    Science.gov (United States)

    Liu, Hui; Yang, Mingjing; Wu, Panpan; Guan, Jiao; Men, Lei; Lin, Hongli; Tang, Xing; Zhao, Yunli; Yu, Zhiguo

    2015-02-01

    In order to investigate the pharmacokinetics of triamcinolone acetonide palmitate (TAP) which is a lipid-soluble prodrug of triamcinolone acetonide (TA), a rapid, simple, sensitive and reproducible UPLC-MS/MS method has been developed and validated for the simultaneous determination of TAP and TA in beagle dog plasma. After simple liquid-liquid extraction, the analytes and internal standard (dexamethasone, DEX) were separated on Phenomenex Luna C18 column (50 mm × 2.1mm, 1.7 μm) using a mobile phase consisting of solvent A (acetonitrile) and solvent B (0.1% ammonia solution) at a flow rate of 0.2 ml/min with gradient elution. Acquisition of mass spectrometric data was performed in multiple reaction monitoring (MRM) mode via positive electrospray ionization using the ion transitions of m/z 673.5→397.3, 435.3→415.3 and 393.3→355.3 for TAP, TA and IS, respectively. The method was of satisfactory specificity, sensitivity, precision and accuracy over the concentration range of 1-1,000 ng/ml for TAP and 0.5-500 ng/ml for TA. The intra- and inter-day precisions for both TAP and TA were 3.2% to 18.7% and the accuracy was in the range of -8.4% to 6.8%. The mean recoveries of TAP, TA and IS were 86.7-104.7%. The method was successfully applied to a long-term pharmacokinetic study of TAP and TA after 28-day repeated intravenous administration of TAP lipid emulsion injection to beagle dogs. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Polymer gel dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Baldock, C [Institute of Medical Physics, School of Physics, University of Sydney (Australia); De Deene, Y [Radiotherapy and Nuclear Medicine, Ghent University Hospital (Belgium); Doran, S [CRUK Clinical Magnetic Resonance Research Group, Institute of Cancer Research, Surrey (United Kingdom); Ibbott, G [Radiation Physics, UT M D Anderson Cancer Center, Houston, TX (United States); Jirasek, A [Department of Physics and Astronomy, University of Victoria, Victoria, BC (Canada); Lepage, M [Centre d' imagerie moleculaire de Sherbrooke, Departement de medecine nucleaire et de radiobiologie, Universite de Sherbrooke, Sherbrooke, QC (Canada); McAuley, K B [Department of Chemical Engineering, Queen' s University, Kingston, ON (Canada); Oldham, M [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Schreiner, L J [Cancer Centre of South Eastern Ontario, Kingston, ON (Canada)], E-mail: c.baldock@physics.usyd.edu.au, E-mail: yves.dedeene@ugent.be

    2010-03-07

    Polymer gel dosimeters are fabricated from radiation sensitive chemicals which, upon irradiation, polymerize as a function of the absorbed radiation dose. These gel dosimeters, with the capacity to uniquely record the radiation dose distribution in three-dimensions (3D), have specific advantages when compared to one-dimensional dosimeters, such as ion chambers, and two-dimensional dosimeters, such as film. These advantages are particularly significant in dosimetry situations where steep dose gradients exist such as in intensity-modulated radiation therapy (IMRT) and stereotactic radiosurgery. Polymer gel dosimeters also have specific advantages for brachytherapy dosimetry. Potential dosimetry applications include those for low-energy x-rays, high-linear energy transfer (LET) and proton therapy, radionuclide and boron capture neutron therapy dosimetries. These 3D dosimeters are radiologically soft-tissue equivalent with properties that may be modified depending on the application. The 3D radiation dose distribution in polymer gel dosimeters may be imaged using magnetic resonance imaging (MRI), optical-computerized tomography (optical-CT), x-ray CT or ultrasound. The fundamental science underpinning polymer gel dosimetry is reviewed along with the various evaluation techniques. Clinical dosimetry applications of polymer gel dosimetry are also presented. (topical review)

  11. Pharmacokinetics of thiamine derivatives especially of benfotiamine.

    Science.gov (United States)

    Loew, D

    1996-02-01

    Pharmacokinetic data of orally administered lipid-soluble thiamine analogues like benfotiamine are reviewed and assessed. It is quite clear that benfotiamine is absorbed much more better than water-soluble thiamine salts: maximum plasma levels of thiamine are about 5 times higher after benfotiamine, the bioavailability is at maximum about 3.6 times as high as that of thiamine hydrochloride and better than other lipophilic thiamine derivates. The physiological activity (alphaETK) increased only after benfotiamine was given. Due to its excellent pharmacokinetic profile benfotiamine should be preferred in treatment of relevant indications.

  12. Pharmacokinetics of mitragynine in man

    Directory of Open Access Journals (Sweden)

    Trakulsrichai S

    2015-04-01

    the study without adverse reactions. The median duration of abuse was 1.75 years. We analyzed one subject separately due to the abnormal behavior of blood concentration. From data of nine subjects, the pharmacokinetic parameters established were time to reach the maximum plasma concentration (0.83±0.35 hour, terminal half-life (23.24±16.07 hours, and the apparent volume of distribution (38.04±24.32 L/kg. The urine excretion of unchanged form was 0.14%. The pharmacokinetics were observed to be oral two-compartment model. Conclusion: This was the first pharmacokinetic study in humans, which demonstrated linearity and was consistent with the oral two-compartment model with a terminal half-life of about 1 day. The pharmacokinetic linearity and parameters reported are necessary pharmacological information of Kratom, and there is a possibility for it to be developed medically as a pain killer or better opioid substitute in the future. Keywords: kratom, human, pharmacokinetics

  13. Theoretical basis for dosimetry

    International Nuclear Information System (INIS)

    Carlsson, G.A.

    1985-01-01

    Radiation dosimetry is fundamental to all fields of science dealing with radiation effects and is concerned with problems which are often intricate as hinted above. A firm scientific basis is needed to face increasing demands on accurate dosimetry. This chapter is an attempt to review and to elucidate the elements for such a basis. Quantities suitable for radiation dosimetry have been defined in the unique work to coordinate radiation terminology and usage by the International Commission on Radiation Units and Measurements, ICRU. Basic definitions and terminology used in this chapter conform with the recent ''Radiation Quantities and Units, Report 33'' of the ICRU

  14. Dosimetry for radiation processing

    International Nuclear Information System (INIS)

    Miller, Arne

    1986-01-01

    During the past few years significant advances have taken place in the different areas of dosimetry for radiation processing, mainly stimulated by the increased interest in radiation for food preservation, plastic processing and sterilization of medical products. Reference services both by international organizations (IAEA) and national laboratories have helped to improve the reliability of dose measurements. In this paper the special features of radiation processing dosimetry are discussed, several commonly used dosimeters are reviewed, and factors leading to traceable and reliable dosimetry are discussed. (author)

  15. Population Pharmacokinetics of Intranasal Scopolamine

    Science.gov (United States)

    Wu, L.; Chow, D. S. L.; Putcha, L.

    2013-01-01

    Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS).The bioavailability and pharmacokinetics (PK) was evaluated using data collected in Phase II IND protocols. We reported earlier statistically significant gender differences in PK parameters of INSCOP at a dose level of 0.4 mg. To identify covariates that influence PK parameters of INSCOP, we examined population covariates of INSCOP PK model for 0.4 mg dose. Methods: Plasma scopolamine concentrations versus time data were collected from 20 normal healthy human subjects (11 male/9 female) after a 0.4 mg dose. Phoenix NLME was employed for PK analysis of these data using gender, body weight and age as covariates for model selection. Model selection was based on a likelihood ratio test on the difference of criteria (-2LL). Statistical significance for base model building and individual covariate analysis was set at P less than 0.05{delta(-2LL)=3.84}. Results: A one-compartment pharmacokinetic model with first-order elimination best described INSCOP concentration ]time profiles. Inclusion of gender, body weight and age as covariates individually significantly reduced -2LL by the cut-off value of 3.84(P less than 0.05) when tested against the base model. After the forward stepwise selection and backward elimination steps, gender was selected to add to the final model which had significant influence on absorption rate constant (ka) and the volume of distribution (V) of INSCOP. Conclusion: A population pharmacokinetic model for INSCOP has been identified and gender was a significant contributing covariate for the final model. The volume of distribution and Ka were significantly higher in males than in females which confirm gender-dependent pharmacokinetics of scopolamine after administration of a 0.4 mg dose.

  16. PHARMACOKINETICS OF PIROXICAM IN CRANES (FAMILY GRUIDAE).

    Science.gov (United States)

    Keiper, Naomi L; Cox, Sherry K; Doss, Grayson A; Elsmo, Betsy; Franzen-Klein, Dana; Hartup, Barry K

    2017-09-01

    To investigate the pharmacokinetics of the nonsteroidal anti-inflammatory drug (NSAID) piroxicam in cranes, three brolgas (Antigone rubicunda) were administered piroxicam as a single oral dose at 0.5 mg/kg and 1.0 mg/kg during separate trials. Serial blood samples were collected for quantification of piroxicam in plasma. Piroxicam was readily absorbed at both dosages, and no adverse effects were observed. Plasma concentrations peaked at 3.67 hr with a concentration of 4.00 μg/ml for the lower dosage, and at 0.83 hr at 8.77 μg/ml for the higher dosage. Piroxicam may exhibit linear kinetics and dose proportionality in brolgas, but will require further study. Mean peak plasma concentrations in brolgas were comparable to concentrations demonstrated to be analgesic in humans. To the authors' knowledge, this study represents the first pharmacokinetic investigation of piroxicam in an avian species.

  17. Simultaneous quantification of acetaminophen and five acetaminophen metabolites in human plasma and urine by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry: Method validation and application to a neonatal pharmacokinetic study.

    Science.gov (United States)

    Cook, Sarah F; King, Amber D; van den Anker, John N; Wilkins, Diana G

    2015-12-15

    Drug metabolism plays a key role in acetaminophen (paracetamol)-induced hepatotoxicity, and quantification of acetaminophen metabolites provides critical information about factors influencing susceptibility to acetaminophen-induced hepatotoxicity in clinical and experimental settings. The aims of this study were to develop, validate, and apply high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) methods for simultaneous quantification of acetaminophen, acetaminophen-glucuronide, acetaminophen-sulfate, acetaminophen-glutathione, acetaminophen-cysteine, and acetaminophen-N-acetylcysteine in small volumes of human plasma and urine. In the reported procedures, acetaminophen-d4 and acetaminophen-d3-sulfate were utilized as internal standards (IS). Analytes and IS were recovered from human plasma (10μL) by protein precipitation with acetonitrile. Human urine (10μL) was prepared by fortification with IS followed only by sample dilution. Calibration concentration ranges were tailored to literature values for each analyte in each biological matrix. Prepared samples from plasma and urine were analyzed under the same HPLC-ESI-MS/MS conditions, and chromatographic separation was achieved through use of an Agilent Poroshell 120 EC-C18 column with a 20-min run time per injected sample. The analytes could be accurately and precisely quantified over 2.0-3.5 orders of magnitude. Across both matrices, mean intra- and inter-assay accuracies ranged from 85% to 112%, and intra- and inter-assay imprecision did not exceed 15%. Validation experiments included tests for specificity, recovery and ionization efficiency, inter-individual variability in matrix effects, stock solution stability, and sample stability under a variety of storage and handling conditions (room temperature, freezer, freeze-thaw, and post-preparative). The utility and suitability of the reported procedures were illustrated by analysis of pharmacokinetic samples

  18. Development and validation of an UFLC-MS/MS method for enantioselectivity determination of d,l-thero-methylphenidate, d,l-thero-ethylphenidate and d,l-thero-ritalinic acid in rat plasma and its application to pharmacokinetic study.

    Science.gov (United States)

    Zhang, Chenghao; Luo, Huafei; Wu, Yubo; Zhang, Junyun; Zhang, Furong; Lin, Guobei; Wang, Hao

    2016-02-01

    A chiral UFLC-MS/MS method was established and validated for quantifying d-threo-methylphenidate (d-threo-MPH), l-threo-methylphenidate (l-threo-MPH), d-threo-ethylphenidate (d-threo-EPH), l-threo-ethylphenidate (l-threo-EPH) and d,l-threo-ritalinic acid (d,l-threo-RA) in rat plasma over the linearity range of 1-500ng/mL. Chiral separation was performed on an Astec Chirobiotic V2 column (5μm, 250×2.1mm) with isocratic elution using methanol containing 0.003% ammonium acetate (w/v) and 0.003% trifluoroacetic acid (v/v) at a flow of 0.3mL/min. All analytes and IS were extracted from rat plasma by a one-step liquid-liquid extraction (LLE) method. The intra- and inter-run accuracies were within 85-115%, and the intra- and inter-run precision were <10% for all analytes. Extraction recoveries were 55-62% for d-threo-MPH, 54-60% for l-threo-MPH, 55-60% for d-threo-EPH, 53-57% for l-threo-EPH and 25-30% for d,l-threo-RA. The validated UFLC-MS/MS method successfully applied to the pharmacokinetic interaction study of oral d-threo-MPH and l-threo-MPH (alone or in combination) in female Sprague Dawley rats. The EPH was not detected in rat plasma following oral administrated MPH without EtOH. As far as it is known to the authors, this study is the first one step liquid-liquid extraction method to extract and UFLC-MS/MS method to quantify d-threo-MPH, l-threo-MPH, d-threo-EPH, l-threo-EPH and d,l-threo-RA simultaneously. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Simultaneous determination of carboprost methylate and its active metabolite carboprost in dog plasma by liquid chromatography-tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application to a pharmacokinetic study.

    Science.gov (United States)

    Yin, Lei; Meng, Xiangjun; Zhou, Xiaotong; Zhang, Tinglan; Sun, Heping; Yang, Zhichao; Yang, Bo; Xiao, Ning; Fawcett, J Paul; Yang, Yan; Gu, Jingkai

    2015-08-15

    A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method using positive/negative electrospray ionization (ESI) switching for the simultaneous quantitation of carboprost methylate and carboprost in dog plasma has been developed and validated. After screening, the esterase inhibitor, dichlorvos was added to the whole blood at a ratio of 1:99 (v/v) to stabilize carboprost methylate during blood collection, sample storage and LLE. Indomethacin was added to plasma to inhibit prostaglandins synthesis after sampling. After liquid-liquid extraction of 500μL plasma with ethyl ether-dichloromethane (75:25, v/v), analytes and internal standard (IS), alprostadil-d4, were chromatographed on a CAPCELL PAK Phenyl column (150×2.0mm, 5μm) using acetonitrile-5mM ammonium acetate as mobile phase. Carboprost methylate was detected by positive ion electrospray ionization followed by multiple reaction monitoring (MRM) of the transition at m/z 400.5→329.3; the carboprost and IS were detected by negative ion electrospray ionization followed by MRM of the transitions at m/z 367.2→323.2, and 357.1→321.2, respectively. The method was linear for both analytes in the concentration range 0.05-30ng/mL with intra- and inter-day precisions (as relative standard deviation) of ≤6.75% and accuracy (as relative error) of ≤7.21% and limit of detection (LOD) values were 10 and 20pg/mL, respectively. The method was successfully applied to a pharmacokinetic study of the analytes in beagle dogs after intravaginal administration of a suppository containing 0.5mg carboprost methylate. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Development and validation of a high-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of irinotecan and its main metabolites in human plasma and its application in a clinical pharmacokinetic study.

    Directory of Open Access Journals (Sweden)

    Elena Marangon

    Full Text Available Irinotecan is currently used in several cancer regimens mainly in colorectal cancer (CRC. This drug has a narrow therapeutic range and treatment can lead to side effects, mainly neutropenia and diarrhea, frequently requiring discontinuing or lowering the drug dose. A wide inter-individual variability in irinotecan pharmacokinetic parameters and pharmacodynamics has been reported and associated to patients' genetic background. In particular, a polymorphism in the UGT1A1 gene (UGT1A1*28 has been linked to an impaired detoxification of SN-38 (irinotecan active metabolite to SN-38 glucuronide (SN-38G leading to increased toxicities. Therefore, therapeutic drug monitoring of irinotecan, SN-38 and SN-38G is recommended to personalize therapy. In order to quantify simultaneously irinotecan and its main metabolites in patients' plasma, we developed and validated a new, sensitive and specific HPLC-MS/MS method applicable to all irinotecan dosages used in clinic. This method required a small plasma volume, addition of camptothecin as internal standard and simple protein precipitation. Chromatographic separation was done on a Gemini C18 column (3 μM, 100 mm x 2.0 mm using 0.1% acetic acid/bidistilled water and 0.1% acetic acid/acetonitrile as mobile phases. The mass spectrometer worked with electrospray ionization in positive ion mode and selected reaction monitoring. The standard curves were linear (R2 ≥0.9962 over the concentration ranges (10-10000 ng/mL for irinotecan, 1-500 ng/mL for SN-38 and SN-38G and 1-5000 ng/mL for APC and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy, determined on three quality control levels for all the analytes, were always <12.3% and between 89.4% and 113.0%, respectively. Moreover, we evaluated this bioanalytical method by re-analysis of incurred samples as an additional measure of assay reproducibility. This method was successfully applied to a pharmacokinetic study in

  1. Dosimetry of internal emitters

    International Nuclear Information System (INIS)

    Anon.

    1982-01-01

    The Dosimetry of Internal Emitter Program endeavors to refine the correlation between radiation dose and observed biological effects. The program is presently engaged in the development of studies that will demonstrate the applicability of microdosimetry models developed under the Microdosimetry of Internal Sources Program. The program also provides guidance and assistance to Pacific Northwest Laboratory's Biology Department in the dosimetric analysis of internally deposited radionuclides. This report deals with alpha particle dosimetry plutonium 239 inhalation, and in vitro studies of chromosomal observations

  2. Individual neutron dosimetry

    International Nuclear Information System (INIS)

    Mauricio, C.L.P.

    1987-01-01

    The most important concepts and development in individual neutron dosimetry are presented, especially the dosimetric properties of the albedo technique. The main problem in albedo dosimetry is to calibrate the dosemeter in the environs of each neutron source. Some of the most used calibration techniques are discussed. The IRD albedo dosemeter used in the routine neutron individual monitoring is described in detail. Its dosimetric properties and calibration methods are discussed. (Author) [pt

  3. JENDL Dosimetry File

    International Nuclear Information System (INIS)

    Nakazawa, Masaharu; Iguchi, Tetsuo; Kobayashi, Katsuhei; Iwasaki, Shin; Sakurai, Kiyoshi; Ikeda, Yujiro; Nakagawa, Tsuneo.

    1992-03-01

    The JENDL Dosimetry File based on JENDL-3 was compiled and integral tests of cross section data were performed by the Dosimetry Integral Test Working Group of the Japanese Nuclear Data Committee. Data stored in the JENDL Dosimetry File are the cross sections and their covariance data for 61 reactions. The cross sections were mainly taken from JENDL-3 and the covariances from IRDF-85. For some reactions, data were adopted from other evaluated data files. The data are given in the neutron energy region below 20 MeV in both of point-wise and group-wise files in the ENDF-5 format. In order to confirm reliability of the data, several integral tests were carried out; comparison with the data in IRDF-85 and average cross sections measured in fission neutron fields, fast reactor spectra, DT neutron fields and Li(d, n) neutron fields. As a result, it has been found that the JENDL Dosimetry File gives better results than IRDF-85 but there are some problems to be improved in future. The contents of the JENDL Dosimetry File and the results of the integral tests are described in this report. All of the dosimetry cross sections are shown in a graphical form. (author) 76 refs

  4. Dosimetry and Calibration Section

    International Nuclear Information System (INIS)

    Otto, T.

    1999-01-01

    The Dosimetry and Calibration Section fulfils two tasks within CERN's Radiation Protection Group: the Individual Dosimetry Service monitors more than 5000 persons potentially exposed to ionizing radiation on the CERN sites, and the Calibration Laboratory verifies throughout the year, at regular intervals, over 1000 instruments, monitors, and electronic dosimeters used by RP Group. The establishment of a Quality Assurance System for the Individual Dosimetry Service, a requirement of the new Swiss Ordinance for personal dosimetry, put a considerable workload on the section. Together with an external consultant it was decided to identify and then describe the different 'processes' of the routine work performed in the dosimetry service. The resulting Quality Manual was submitted to the Federal Office for Public Health in Bern in autumn. The CERN Individual Dosimetry Service will eventually be officially endorsed after a successful technical test in March 1999. On the technical side, the introduction of an automatic development machine for gamma films was very successful. It processes the dosimetric films without an operator being present, and its built-in regeneration mechanism keeps the concentration of the processing chemicals at a constant level

  5. JENDL Dosimetry File

    Energy Technology Data Exchange (ETDEWEB)

    Nakazawa, Masaharu; Iguchi, Tetsuo [Tokyo Univ. (Japan). Faculty of Engineering; Kobayashi, Katsuhei [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst.; Iwasaki, Shin [Tohoku Univ., Sendai (Japan). Faculty of Engineering; Sakurai, Kiyoshi; Ikeda, Yujior; Nakagawa, Tsuneo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1992-03-15

    The JENDL Dosimetry File based on JENDL-3 was compiled and integral tests of cross section data were performed by the Dosimetry Integral Test Working Group of the Japanese Nuclear Data Committee. Data stored in the JENDL Dosimetry File are the cross sections and their covariance data for 61 reactions. The cross sections were mainly taken from JENDL-3 and the covariances from IRDF-85. For some reactions, data were adopted from other evaluated data files. The data are given in the neutron energy region below 20 MeV in both of point-wise and group-wise files in the ENDF-5 format. In order to confirm reliability of the data, several integral tests were carried out; comparison with the data in IRDF-85 and average cross sections measured in fission neutron fields, fast reactor spectra, DT neutron fields and Li(d,n) neutron fields. As a result, it has been found that the JENDL Dosimetry File gives better results than IRDF-85 but there are some problems to be improved in future. The contents of the JENDL Dosimetry File and the results of the integral tests are described in this report. All of the dosimetry cross sections are shown in a graphical form.

  6. Population pharmacokinetics and relationship between demographic and clinical variables and pharmacokinetics of gentamicin in neonates

    NARCIS (Netherlands)

    Stolk, L M L; Degraeuwe, P L J; Nieman, F H M; de Wolf, M C; de Boer, A|info:eu-repo/dai/nl/075097346

    Population pharmacokinetic parameter estimates were calculated from 725 routine plasma gentamicin concentrations obtained in 177 neonates of 24 to 42 weeks' gestational age in their first week of life. Kel increases and V/W decreases with increasing gestational age. Almost identical results were

  7. An HPLC method for the quantitation of 3-pentylbenzo[c]thiophen-1(3H)-one in dog plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Li, Ting-Ting; Hua, Kai; Sheng, Xiao; Liu, Ling; Tan, Jia-Ni; Wang, Lin-Na; Wei, Bo; Ji, Hui; Zhang, Yi-Hua

    2014-12-01

    A simple, sensitive and reproducible high-performance liquid chromatography (HPLC) assay method was developed for the estimation of 3-pentylbenzo[c]thiophen-1(3H)-one (S5 ), a potential anti-ischemic stroke agent, in dog plasma. The analytical procedure involves protein precipitation of S5 and nobiletin (internal standard) from dog plasma with acetonitrile. Chromatographic separation was achieved on Sapphire C18 analytical column with methanol-water (80:20, v/v) as mobile phase. The eluate was monitored using a UV detector set at 260 nm. The calibration curves were linear over the range of 0.2-20 µg/mL. Absolute recoveries of S5 were 79.2-86.1% from dog plasma. The intra- and inter-day relative standard deviation precisions were dogs. Copyright © 2014 John Wiley & Sons, Ltd.

  8. Pharmacokinetics of enrofloxacin and ceftiofur in plasma, interstitial fluid, and gastrointestinal tract of calves after subcutaneous injection, and bactericidal impacts on representative enteric bacteria.

    Science.gov (United States)

    Foster, D M; Jacob, M E; Warren, C D; Papich, M G

    2016-02-01

    This study's objectives were to determine intestinal antimicrobial concentrations in calves administered enrofloxacin or ceftiofur sodium subcutaneously, and their impact on representative enteric bacteria. Ultrafiltration devices were implanted in the ileum and colon of 12 steers, which received either enrofloxacin or ceftiofur sodium. Samples were collected over 48 h after drug administration for pharmacokinetic/pharmacodynamic analysis. Enterococcus faecalis or Salmonella enterica (5 × 10(5) CFU/mL of each) were exposed in vitro to peak and tail (48 h postadministration) concentrations of both drugs at each location for 24 h to determine inhibition of growth and change in MIC. Enrofloxacin had tissue penetration factors of 1.6 and 2.5 in the ileum and colon, while ciprofloxacin, an active metabolite of enrofloxacin, was less able to cross into the intestine (tissue penetration factors of 0.7 and 1.7). Ceftiofur was rapidly eliminated leading to tissue penetration factors of 0.39 and 0.25. All concentrations of enrofloxacin were bactericidal for S. enterica and significantly reduced E. faecalis. Peak ceftiofur concentration was bactericidal for S. enterica, and tail concentrations significantly reduced growth. E. faecalis experienced growth at all ceftiofur concentrations. The MICs for both organisms exposed to peak and tail concentrations of antimicrobials were unchanged at the end of the study. Enrofloxacin and ceftiofur achieved intestinal concentrations capable of reducing intestinal bacteria, yet the short exposure of ceftiofur in the intestine may select for resistant organisms. © 2015 John Wiley & Sons Ltd.

  9. Image in nuclear dosimetry using thermoluminescent dosimetry

    International Nuclear Information System (INIS)

    Guinsburg, G.; Matsuoka, M.; Watanabe, S.

    1987-01-01

    A low cost methodology to produce images of internal sick organs by radioisotopic intake, is presented. Dosimetries of thermoluminescent material and Teflon (ratio:50%) in bidimensional matrix shape are used with a Pb collimator. This collimator-bidimensional matrix system was tested ''in vivo'' and in thyroid phantoms using 99m Tc. A comparative evaluation between this method and the scintigraphy one is presented. (M.A.C.) [pt

  10. Determination of telmisartan in human blood plasma: Part II: Liquid chromatography-tandem mass spectrometry method development, comparison to immunoassay and pharmacokinetic study

    NARCIS (Netherlands)

    Hempen, C.M.; Gläsle-Schwarz, Liane; Kunz, Ulrich; Karst, U.

    2006-01-01

    A new liquid chromatography/atmospheric pressure chemical ionization-tandem mass spectrometry (LC/APCI-MS/MS) method with on-line sample clean-up for the determination of telmisartan in human blood plasma is presented. This technique is compared to a previously introduced enzyme-linked immunosorbent

  11. Pharmacokinetics and Plasma Cellular Antioxidative Effects of Flavanols After Oral Intake of Green Tea Formulated with Vitamin C and Xylitol in Healthy Subjects.

    Science.gov (United States)

    Son, Yu-Ra; Park, Tae-Sik; Shim, Soon-Mi

    2016-02-01

    This study aimed to test whether green tea formulated with vitamin C and xylitol (GTVX) could improve absorption of flavanols and total antioxidant activity (TAC) of plasma compared with green tea only (GT) in healthy subjects. The total radical-trapping antioxidant parameter method was used to measure the TAC of plasma. Cmax, Tmax, and area under the curve (AUC) of flavanols in plasma after consumption of GTVX were 5980.58 μg/mL, 2.14 h, and 18,915.56 h·μg/mL, respectively, indicating that GTVX showed significantly higher AUC than GT (13,855.43 μg/mL). The peak TACs occurred at 3 and 0.5 h after intake of GT and GTVX, respectively. The TAC of plasma was found to be significantly higher in GTVX than in GT at each time point. This study suggests that formulating green tea with vitamin C and xylitol could increase the absorption of flavanols in green tea, enhancing cellular antioxidative effects.

  12. Simultaneous determination of the novel tyrosine kinase inhibitor meditinib and its active metabolite demethylation meditinib in monkey plasma by liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic studies.

    Science.gov (United States)

    Liang, Feng; Kong, Qi; Guo, Yongqi; Wang, Yu; Sun, Dejie; Liu, Shi; Cai, Jinling; Guan, Yongbiao; Ding, Rigao

    2015-08-01

    Meditinib (ME) is a novel tyrosine kinase inhibitor used as an antichronic myeloid leukemia drug. A simple, sensitive and specific LC/MS/MS method was developed and validated for the analysis of ME and its metabolite demethylation meditinib (PI) in monkey plasma using naltrexone as the internal standard. Sample preparation involved protein precipitation with methanol. The analysis was carried out on an Agilent C8 column (3.5 µm, 2.1 × 50 mm). Elution was achieved with a mobile phase gradient varying the proportion of a water solution containing 0.1% formic acid (solvent A) and a 0.1% formic acid in methanol solution (solvent B) at a flow rate of 300 μL/min. The method had a linear calibration curve over the concentration range of 2-1000 ng/mL for ME and 2-1000 ng/mL for PI. The lower limits of quantification of ME and PI were 2 and 2 ng/mL, respectively. The intra- and inter-day precision values were 85%. The assay has been successfully used for pharmacokinetic evaluation of ME and PI using the monkey as an animal model, and those data are reported for the first time. Copyright © 2015 John Wiley & Sons, Ltd.

  13. 6-[Fluorine-18]Fluorodopamine pharmacokinetics and dosimetry in humans

    International Nuclear Information System (INIS)

    Goldstein, D.S.; Coronado, L.; Kopin, I.J.

    1994-01-01

    PET scanning after injection of 6-[ 18 F]fluorodopamine visualizes tissue sympathetic innervation. Organ dosimetric estimates for 6-[ 18 F]fluorodopamine have relied on studies of rats and dogs and on literature about the fate of other radiolabeled catecholamines. This report uses empirical clinical findings in healthy volunteers to refine and extend these estimates. Thoracic PET scanning was conducted and arterial blood and urine samples were obtained after intravenous injection of 6-[ 18 F]fluorodopamine into 10 normal volunteers. The main target organs for 6-[ 18 F]fluorodopamine-derived radioactivity were the wall of the urinary bladder (3.3 rem for a 4-mCi dose and 3.31-hr voiding interval) and the kidneys (2.9 rem for a 4-mCi dose) due to urinary excretion of radioactive metabolites of [ 18 F]-6F-DA. The estimates were about one-fourth those predicted from studies of laboratory animals. At administered doses required to visualize the left ventricular myocardium in humans, a 6-[ 18 F]fluorodopamine injection produces acceptable absorbed radiation doses, with the highest doses to the urinary collecting system. 22 refs., 2 figs., 5 tabs

  14. Absorption and pharmacokinetics of grapefruit flavanones in beagles

    OpenAIRE

    Mata Bilbao, María de Lourdes; Andrés Lacueva, Ma. Cristina; Roura Carvajal, Elena; Jáuregui Pallarés, Olga; Escribano Ferrer, Elvira; Torre, Celina; Lamuela Raventós, Rosa Ma.

    2007-01-01

    The present study evaluated the pharmacokinetics of three different grapefruit flavanone forms in dog plasma and demonstrated their absorption after an oral intake of a grapefruit extract; pharmacokinetic parameters of these forms were also determined. Ten healthy beagles were administered 70 mg citrus flavonoids as a grapefruit extract contained in capsules, while two additional dogs were used as controls and given an excipient. The grapefruit flavanone naringin, along with its metabolites n...

  15. Simultaneous determination of bioactive components in essential oil of Xiang-Fu-Si-Wu Formula in Beagle dog plasma by UPLC-MS/MS and its application to pharmacokinetics.

    Science.gov (United States)

    Liu, Pei; Li, Zhenhao; Qian, Dawei; Li, Wei; Shang, Er-Xin; Duan, Jin-Ao

    2013-06-15

    A highly sensitive and rapid ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed and validated for simultaneous quantification of the three main bioactive compounds, i.e., ligustilide, dehydrocostuslactone and α-cyperone in dog plasma after oral administration of the essential oil of Xiang-Fu-Si-Wu Formula (XEO). Clarithromycin was used as an internal standard (IS). Plasma samples were processed by protein precipitation with methanol. The separation was performed on an Acquity BEH C18 column (100mm×2.1mm, 1.7μm) at a flow rate of 0.4mLmin(-1), using 0.1% formic acid-acetonitrile as mobile phase. The MS/MS ion transit ions monitored were 190.5→90.9 for ligustilide, 231.1→185.1 for dehydrocostuslactone, 219.2→123.0 for α-cyperone and 748.5→158.1 for IS. Method validation was performed as per Food and Drug Administration guidelines and the results met the acceptance criteria. The lower limit of quantification (LLOQ) achieved was 5.12ng/mL for ligustilide, 1.06ng/mL for dehydrocostuslactone and 1.89ng/mL for α-cyperone, respectively, and the calibration curves obtained were linear (r>0.99) over the concentration range approximately 1-1000ng/mL. The intra- and inter-day precision was less than 15% and the accuracy was within ±9.2%. After validation, this method was successfully applied to a pharmacokinetic study where dogs were orally given 0.3g/kg XEO, equivalent to 183.6mg/kg of ligustilide, 5.0mg/kg of dehydrocostuslactone and 26.2mg/kg of α-cyperone, respectively. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Development and validation of a sensitive UHPLC-MS/MS method for the simultaneous analysis of tramadol, dextromethorphan chlorpheniramine and their major metabolites in human plasma in forensic context: application to pharmacokinetics.

    Science.gov (United States)

    Heneedak, Hala M; Salama, Ismail; Mostafa, Samia; El-Kady, Ehab; El-Sadek, Mohamed

    2015-07-01

    The prerequisites for forensic confirmatory analysis by LC/MS/MS with respect to European Union guidelines are chromatographic separation, a minimum number of two MS/MS transitions to obtain the required identification points and predefined thresholds for the variability of the relative intensities of the MS/MS transitions (MRM transitions) in samples and reference standards. In the present study, a fast, sensitive and robust method to quantify tramadol, chlorpheniramine, dextromethorphan and their major metabolites, O-desmethyltramadol, dsmethyl-chlorpheniramine and dextrophan, respectively, in human plasma using ibuprofen as internal standard (IS) is described. The analytes and the IS were extracted from plasma by a liquid-liquid extraction method using ethyl acetate-diethyl-ether (1:1). Extracted samples were analyzed by ultra-high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). Chromatographic separation was performed by pumping the mobile phase containing acetonitrile, water and formic acid (89.2:11.7:0.1) for 2.0 min at a flow rate of 0.25 μL/min into a Hypersil-Gold C18 column, 20 × 2.0 mm (1.9 µm) from Thermoscientific, New York, USA. The calibration curve was linear for the six analytes. The intraday precision (RSD) and accuracy (RE) of the method were 3-9.8 and -1.7-4.5%, respectively. The analytical procedure herein described was used to assess the pharmacokinetics of the analytes in 24 healthy volunteers after a single oral dose containing 50 mg of tramadol hydrochloride, 3 mg chlorpheniramine maleate and 15 mg of dextromethorphan hydrobromide. Copyright © 2014 John Wiley & Sons, Ltd.

  17. Simultaneous determination of asperosaponin VI and its active metabolite hederagenin in rat plasma by liquid chromatography-tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application in pharmacokinetic study.

    Science.gov (United States)

    Zhu, He; Ding, Li; Shakya, Shailendra; Qi, Xiemin; Hu, Linlin; Yang, Xiaolin; Yang, Zhonglin

    2011-11-15

    substances from the rat plasma. The validated method was successfully applied to study the pharmacokinetics of asperosaponin VI and its active metabolite hederagenin in rat plasma after oral administration of asperosaponin VI at a dose of 90 mg/kg. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Pharmacokinetics: curiosity or cure

    International Nuclear Information System (INIS)

    Notari, R.E.

    1979-01-01

    What is the fate of a drug from the time of its introduction into the body to the end of its duration. Pharmacokinetic studies are often designed to provide an answer to this question. But this question may be asked of any drug and research that is limited to answering it will remain empirical. Pharmacokinetic studies can provide answers to many other drug-related questions. In doing so pharmacokinetic research has the potential of improving drug therapy as well as the design and evaluation of drugs. While significant contributions can be cited, the future of pharmacokinetics depends upon its increased impact on clinical practice and drug design. How can a molecule be tailored for site specificity. Can chemical modification selectively alter absorption, distribution, metabolism, binding or excretion. In what new ways can pharmacokinetic information increase the predictability of drug therapy. Such questions, to which pharmacokinetics should provide answers, are numerous and easily identified. But the definitive studies are difficult both to create and conduct. Whether or not pharmacokinetics can achieve its full potential will depend upon the extent to which it can provide answers to these currently unanswered questions

  19. Lisdexamfetamine: A pharmacokinetic review.

    Science.gov (United States)

    Comiran, Eloisa; Kessler, Félix Henrique; Fröehlich, Pedro Eduardo; Limberger, Renata Pereira

    2016-06-30

    Lisdexamfetamine (LDX) is a d-amphetamine (d-AMPH) pro-drug used to treat Attention Deficit and Hyperactivity Disorder (ADHD) and Binge Eating Disorder (BED) symptoms. The in vivo pharmacodynamics of LDX is the same as that of its active product d-AMPH, although there are a few qualitative and quantitative differences due to pharmacokinetics. Due to the specific pharmacokinetics of the long-acting stimulants, this article revises the pharmacokinetic studies on LDX, the newest amphetamine pro-drug. The Medline/Pubmed, Science Direct and Biblioteca Virtual em Saúde (Lilacs and Ibecs) (2007-2016) databases were searched for articles and their list of references. As for basic pharmacokinetics studies, since LDX is a newly developed medication, there are few results concerning biotransformation, distribution and the use of different biological matrices for analysis. This is the first robust review on this topic, gathering data from all clinical pharmacokinetics studies available in the literature. The particular pharmacokinetics of LDX plays a major role in studying this pro-drug, since this knowledge was essential to understand some reports on clinical effects in literature, e.g. the small likelihood of reducing the effect by interactions, the effect of long duration use and the still questionable reduction of the potential for abuse. In general the already well-known pharmacokinetic properties of amphetamine make LDX relatively predictable, simplifying the use of LDX in clinical practice. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Simultaneous quantification of triterpenoid saponins in rat plasma by UHPLC-MS/MS and its application to a pharmacokinetic study after oral total saponin of Aralia elata leaves.

    Science.gov (United States)

    Sun, Yichun; Xue, Juan; Li, Baimei; Lin, Xiaoting; Wang, Zhibin; Jiang, Hai; Zhang, Hongwei; Wang, Qiuhong; Kuang, Haixue

    2016-11-01

    A rapid, sensitive, and reliable analytical ultra performance liquid chromatography with tandem mass spectrometry method was developed for the simultaneous determination of Aralia-saponin IV, 3-O-β-d-glucopyranosyl-(1→3)-β-d-glucopyranosyl-(1→3)-β-d-glucopyranosyl oleanolic acid 28-O-β-d-glucopyranoside, Aralia-saponin A and Aralia-saponin B after the oral administration of total saponin of Aralia elata leaves in rat plasma. Plasma samples were pretreated by protein precipitation with methanol. The analysis was performed on an ACQUITY UPLC HSS T3 column. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode using an electrospray ionization source with negative ionization mode. Under the experimental conditions, the calibration curves of four analytes had good linearity values (r > 0.991). The intra- and inter-day precision values of the four analytes were ≤ 11.6%, and the accuracy was between -6.2 and 4.2%.The extraction recoveries of four triterpenoid saponins were in the range of 84.06-91.66% (RSD saponins in rat plasma after oral administration of total saponin of Aralia elata leaves, which helps guiding clinical usage of Aralia elata leaves. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Secondary standard dosimetry laboratory (SSDL)

    International Nuclear Information System (INIS)

    Md Saion bin Salikin.

    1983-01-01

    A secondary Standard Dosimetry Laboratory has been established in the Tun Ismail Research Centre, Malaysia as a national laboratory for reference and standardization purposes in the field of radiation dosimetry. This article gives brief accounts on the general information, development of the facility, programmes to be carried out as well as other information on the relevant aspects of the secondary standard dosimetry laboratory. (author)

  2. [Pharmacokinetics of crocetin in rats].

    Science.gov (United States)

    Liu, Tong-zheng; Qian, Zhi-yu

    2002-05-01

    To develop an HPLC method for the determination of crocetin in rat plasma and study the pharmacokinetics in rats. Hypersil C18 column (5 microns, 4.6 mm x 200 mm) was used at column temperature 30 degrees C. The mobile phase consisted of methanol-water-acetic acid (75:24.5:0.5) at the flow rate of 1.0 mL.min-1. The UV detection wave length was 423 nm. The calibration curve was linear (gamma = 0.9996) in the range from 0.49 microgram.mL-1 to 7.87 micrograms.mL-1 for crocetin. The mean recovery was 105.2%. The lowest detectable concentration of crocetin was 0.14 microgram.mL-1 (S/N = 3). The RSDs of within-day and between-day were all less than 5%. The plasma crocetin was steady. The HPLC method of determination of crocetin in the plasma was established. After single dose of 50 mg.kg-1 ig in 10 rats, the main pharmacokinetic parameters were estimated as follows: T1/2 alpha (30 +/- 6) min, Tmax(65 +/- 16) min, Cmax(5.0 +/- 1.0) microgram.mL-1, AUC0-T(845 +/- 109) microgram.min.mL-1, Vd(5.0 +/- 0.8) L.kg-1. Crocetin was shown to be absorbed into the blood through the gastrointestinal tract. This method is quick, precise and reliable. Crocetin was shown to be quickly absorbed in rats.

  3. Neutron dosimetry in biology

    International Nuclear Information System (INIS)

    Sigurbjoernsson, B.; Smith, H.H.; Gustafsson, A.

    1965-01-01

    To study adequately the biological effects of different energy neutrons it is necessary to have high-intensity sources which are not contaminated by other radiations, the most serious of which are gamma rays. An effective dosimetry must provide an accurate measure of the absorbed dose, in biological materials, of each type of radiation at any reactor facility involved in radiobiological research. A standardized biological dosimetry, in addition to physical and chemical methods, may be desirable. The ideal data needed to achieve a fully documented dosimetry has been compiled by H. Glubrecht: (1) Energy spectrum and intensity of neutrons; (2) Angular distribution of neutrons on the whole surface of the irradiated object; (3) Additional undesired radiation accompanying the neutrons; (4) Physical state and chemical composition of the irradiated object. It is not sufficient to note only an integral dose value (e.g. in 'rad') as the biological effect depends on the above data

  4. INDIVIDUAL DOSIMETRY SERVICE

    CERN Multimedia

    2000-01-01

    Personnel in the distribution groups Aleph, Delphi, L3, Opal who also work for other experiments than at LEP, should contact their dispatchers to explain their activities for the future, after LEP dismantling in order to be maintained on the regular distribution list at Individual DosimetryWe inform all staff and users under regular dosimetric control that the dosimeters for the monitoring period MAY/JUNE will be available from their usual dispatchers on Tuesday 2 May.Please have your films changed before the 12 May.The colour of the dosimeter valid in is MAY/JUNE is YELLOW.Individual Dosimetry Service will be closed on Friday 28 April.

  5. Nuclear medicine radiation dosimetry

    CERN Document Server

    McParland, Brian J

    2010-01-01

    Complexities of the requirements for accurate radiation dosimetry evaluation in both diagnostic and therapeutic nuclear medicine (including PET) have grown over the past decade. This is due primarily to four factors: growing consideration of accurate patient-specific treatment planning for radionuclide therapy as a means of improving the therapeutic benefit, development of more realistic anthropomorphic phantoms and their use in estimating radiation transport and dosimetry in patients, design and use of advanced Monte Carlo algorithms in calculating the above-mentioned radiation transport and

  6. Pharmacokinetics of linezolid in critically ill patients.

    Science.gov (United States)

    Sazdanovic, Predrag; Jankovic, Slobodan M; Kostic, Marina; Dimitrijevic, Aleksandra; Stefanovic, Srdjan

    2016-06-01

    Linezolid is an oxazolidinone antibiotic active against Gram-positive bacteria, and is most commonly used to treat life-threatening infections in critically ill patients. The pharmacokinetics of linezolid are profoundly altered in critically ill patients, partly due to decreased function of vital organs, and partly because life-sustaining drugs and devices may change the extent of its excretion. This article is summarizes key changes in the pharmacokinetics of linezolid in critically ill patients. The changes summarized are clinically relevant and may serve as rationale for dosing recommendations in this particular population. While absorption and penetration of linezolid to tissues are not significantly changed in critically ill patients, protein binding of linezolid is decreased, volume of distribution increased, and metabolism may be inhibited leading to non-linear kinetics of elimination; these changes are responsible for high inter-individual variability of linezolid plasma concentrations, which requires therapeutic plasma monitoring and choice of continuous venous infusion as the administration method. Acute renal or liver failure decrease clearance of linezolid, but renal replacement therapy is capable of restoring clearance back to normal, obviating the need for dosage adjustment. More population pharmacokinetic studies are necessary which will identify and quantify the influence of various factors on clearance and plasma concentrations of linezolid in critically ill patients.

  7. Development and validation of an LC-MS/MS method for the determination of mesalazine in beagle dog plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Qin, Juan; Di, Xin; Wang, Xin; Liu, Youping

    2015-02-01

    A simple, specific and sensitive LC-MS/MS method was developed and validated for the determination of mesalazine in beagle dog plasma. The plasma samples were prepared by protein precipitation, then the separation of the analyte was achieved on a Waters Spherisorb C6 column (150 × 4.6 mm, 5 µm) with a mobile phase consisting of 0.2% formic acid in water-methanol (20:80, v/v). The flow rate was set at 1.0 mL/min with a split ratio of 3:2. Mass spectrometric detection was achieved by a triple-quadrupole mass spectrometer equipped with an electrospray source interface in positive ionization mode. Quantitation was performed using selected reaction monitoring of precursor-product ion transitions at m/z 154 → m/z 108 for mesalazine and m/z 285 → m/z 193 for diazepam (internal standard). The linear calibration curve of mesalazine was obtained over the concentration range 50-30,000 ng/mL. The matrix effect of mesalazine was within ±9.8%. The intra- and inter-day precisions were dogs after rectal administration of mesalazine suppository. Copyright © 2014 John Wiley & Sons, Ltd.

  8. Pharmacokinetics of metformin during pregnancy.

    Science.gov (United States)

    Eyal, Sara; Easterling, Thomas R; Carr, Darcy; Umans, Jason G; Miodovnik, Menachem; Hankins, Gary D V; Clark, Shannon M; Risler, Linda; Wang, Joanne; Kelly, Edward J; Shen, Danny D; Hebert, Mary F

    2010-05-01

    Our objective was to evaluate the pharmacokinetics of metformin during pregnancy. Serial blood and urine samples were collected over one steady-state dosing interval in women treated with metformin during early to late pregnancy (n = 35) and postpartum (n = 16). Maternal and umbilical cord blood samples were obtained at delivery from 12 women. Metformin concentrations were also determined in breast milk samples obtained over one dosing interval in 6 women. Metformin renal clearance increased significantly in mid (723 +/- 243 ml/min, P pregnancy (625 +/- 130 ml/min, P metformin net secretion clearance (480 +/- 190 ml/min, P pregnancy versus postpartum, respectively. Metformin concentrations at the time of delivery in umbilical cord plasma ranged between nondetectable (metformin through breast milk was 0.13 to 0.28 mg, and the relative infant dose was metformin pharmacokinetics are affected by pregnancy-related changes in renal filtration and net tubular transport and can be roughly estimated by the use of creatinine clearance. At the time of delivery, the fetus is exposed to metformin concentrations from negligible to as high as maternal concentrations. In contrast, infant exposure to metformin through the breast milk is low.

  9. Pharmacokinetics of Snake Venom

    OpenAIRE

    Suchaya Sanhajariya; Stephen B. Duffull; Geoffrey K. Isbister

    2018-01-01

    Understanding snake venom pharmacokinetics is essential for developing risk assessment strategies and determining the optimal dose and timing of antivenom required to bind all venom in snakebite patients. This review aims to explore the current knowledge of snake venom pharmacokinetics in animals and humans. Literature searches were conducted using EMBASE (1974–present) and Medline (1946–present). For animals, 12 out of 520 initially identified studies met the inclusion criteria. In general, ...

  10. Pharmacokinetic comparison of seven 8-methoxypsoralen brands

    DEFF Research Database (Denmark)

    Menne, T; Andersen, Klaus Ejner; Larsen, E

    1981-01-01

    The pharmacokinetics of seven 8-MOP brands were evaluated in 7 volunteers using an incomplete bloc design. After a single oral dose the 8-MOP plasma level was followed for 3 hours. The plasma concentration was measured with a gas chromatographic - mass spectrometric method, using an isotopic...... dilution technique. The different brands could be divided into three groups. Two gave a high maximum concentration, four a medium, and one a low concentration. The large interbrand variation observed in this study can explain the variations in the results of the treatment and the differing numbers...

  11. Personnel photographic film dosimetry

    International Nuclear Information System (INIS)

    Keirim-Markus, I.B.

    1981-01-01

    Technology of personnel photographic film dosimetry (PPD) based on the photographic effect of ionizing radiation is described briefly. Kinds of roentgen films used in PPD method are enumerated, compositions of a developer and fixing agents for these films are given [ru

  12. Dosimetry and Calibration Section

    International Nuclear Information System (INIS)

    Otto, T.

    1998-01-01

    The two tasks of the Dosimetry and Calibration Section at CERN are the Individual Dosimetry Service which assures the personal monitoring of about 5000 persons potentially exposed to ionizing radiation at CERN, and the Calibration Laboratory which verifies all the instruments and monitors. This equipment is used by the sections of the RP Group for assuring radiation protection around CERN's accelerators, and by the Environmental Section of TISTE. In addition, nearly 250 electronic and 300 quartz fibre dosimeters, employed in operational dosimetry, are calibrated at least once a year. The Individual Dosimetry Service uses an extended database (INDOS) which contains information about all the individual doses ever received at CERN. For most of 1997 it was operated without the support of a database administrator as the technician who had assured this work retired. The Software Support Section of TIS-TE took over the technical responsibility of the database, but in view of the many other tasks of this Section and the lack of personnel, only a few interventions for solving immediate problems were possible

  13. Dosimetry of pion beams

    International Nuclear Information System (INIS)

    Dicello, J.F.

    1975-01-01

    Negative pion beams are probably the most esoteric and most complicated type of radiation which has been suggested for use in clinical radiotherapy. Because of the limited availability of pion beams in the past, even to nuclear physicists, there exist relatively fewer basic data for this modality. Pion dosimetry is discussed

  14. High frequency electromagnetic dosimetry

    CERN Document Server

    Sánchez-Hernández, David A

    2009-01-01

    Along with the growth of RF and microwave technology applications, there is a mounting concern about the possible adverse effects over human health from electromagnetic radiation. Addressing this issue and putting it into perspective, this groundbreaking resource provides critical details on the latest advances in high frequency electromagnetic dosimetry.

  15. Group: radiation dosimetry

    International Nuclear Information System (INIS)

    Caldas, L.V.E.

    1990-01-01

    The main activities of the radiation dosimetry group is described, including the calibration of instruments, sources and radioactive solutions and the determination of neutron flux; development, production and market dosimetric materials; development radiation sensor make the control of radiation dose received by IPEN workers; development new techniques for monitoring, etc. (C.G.C.)

  16. Glucinium dosimetry in beryl

    International Nuclear Information System (INIS)

    Kremer, M.

    1949-05-01

    The application of the method developed by Kolthoff and Sandell (1928) for the dosimetry of glucinium (beryllium) in beryl gives non-reproducible results with up to 20% discrepancies. This method recommends to separate beryllium and aluminium using 8 hydroxyquinoline and then to directly precipitate glucinium in the filtrate using ammonia. One possible reason of the problems generated by this method should be the formation of a volatile complex between beryllium and the oxine. This work shows that when the oxine is eliminated before the precipitation with ammonia the dosimetry of beryllium becomes accurate. The destruction of the oxine requires the dry evaporation of the filtrate, which is a long process. Thus the search for a reagent allowing the quantitative precipitation of beryllium in its solutions and in presence of oxine has been made. It has been verified also that the quantitative precipitation of the double beryllium and ammonium phosphate is not disturbed by the oxine in acetic buffer. This method, which gives good results, has also the advantage to separate beryllium from the alkaline-earth compounds still present in the filtrate. The report details the operation mode of the method: beryllium dosimetry using ammonium phosphate, aluminium-beryllium separation, application to beryl dosimetry (ore processing, insolubilization of silica, precipitation with ammonia, precipitation with oxine, precipitation of PO 4 NH 4 Gl, preciseness). (J.S.)

  17. Instrumentation in thermoluminescence dosimetry

    International Nuclear Information System (INIS)

    Julius, H.W.

    1986-01-01

    In the performance of a thermoluminescence dosimetry (TLD) system the equipment plays an important role. Crucial parameters of instrumentation in TLD are discussed in some detail. A review is given of equipment available on the market today - with some emphasis on automation - which is partly based on information from industry and others involved in research and development. (author)

  18. Solid state radiation dosimetry

    International Nuclear Information System (INIS)

    Moran, P.R.

    1976-01-01

    Important recent developments provide accurate, sensitive, and reliable radiation measurements by using solid state radiation dosimetry methods. A review of the basic phenomena, devices, practical limitations, and categories of solid state methods is presented. The primary focus is upon the general physics underlying radiation measurements with solid state devices

  19. Dosimetry and shielding

    International Nuclear Information System (INIS)

    Farinelli, U.

    1977-01-01

    Today, reactor dosimetry and shielding have wide areas of overlap as concerns both problems and methods. Increased interchange of results and know-how would benefit both. The areas of common interest include calculational methods, sensitivity studies, theoretical and experimental benchmarks, cross sections and other nuclear data, multigroup libraries and procedures for their adjustment, experimental techniques and damage functions. This paper reviews the state-of-the-art and the latest development in each of these areas as far as shielding is concerned, and suggests a number of interactions that could be profitable for reactor dosimetry. Among them, re-evaluation of the potentialities of calculational methods (in view of the recent developments) in predicting radiation environments of interest; the application of sensitivity analysis to dosimetry problems; a common effort in the field of theoretical benchmarks; the use of the shielding one-material propagation experiments as reference spectra for detector cross sections; common standardization of the detector nuclear data used in both fields; the setting up of a common (or compatible) multigroup structure and library applicable to shielding, dosimetry and core physics; the exchange of information and experience in the fields of cross section errors, correlations and adjustment; and the intercomparison of experimental techniques

  20. Influence of chronic renal failure on captopril pharmacokinetics and clinical and biological effects in hypertensive patients.

    OpenAIRE

    Giudicelli, J F; Chaignon, M; Richer, C; Giroux, B; Guedon, J

    1984-01-01

    The pharmacokinetic parameters of unchanged plasma captopril and the kinetics of the drug effects on plasma converting enzyme activity (PCEA), plasma renin activity (PRA), plasma aldosterone (PA) and mean blood pressure (MBP) were studied over 24 h after oral administration in three groups of hypertensive patients: with normal renal function (group 1, plasma creatinine less than 110 mumol/l, n = 10), with moderate chronic renal failure (group 2, 135 less than plasma creatinine less than 450 m...

  1. A simple LC-MS/MS method facilitated by salting-out assisted liquid-liquid extraction to simultaneously determine trans-resveratrol and its glucuronide and sulfate conjugates in rat plasma and its application to pharmacokinetic assay.

    Science.gov (United States)

    Qiu, Zhixia; Yu, Jiaojiao; Dai, Yu; Yang, Yue; Lu, Xiaoyu; Xu, Jiaqiu; Qin, Zhiying; Huang, Fang; Li, Ning

    2017-11-01

    A simple LC-MS/MS method facilitated by salting-out assisted liquid-liquid extraction (SALLE) was applied to simultaneously investigate the pharmacokinetics of trans-resveratrol (Res) and its major glucuronide and sulfate conjugates in rat plasma. Acetonitrile-methanol (80:20, v/v) and ammonium acetate (10 mol L -1 ) were used as extractant and salting-out reagent to locate the target analytes in the supernatant after the aqueous and organic phase stratification, then the analytes were determined via gradient elution by LC-MS/MS in negative mode in a single run. The analytical method was validated with good selectivity, acceptable accuracy (>85%) and low variation of precision (extraction efficiency of target glucuronide and sulfate conjugates (>80%). The method was successfully applied to determine Res and its four conjugated metabolites in rat after Res administration (intragastric, 50 mg kg -1 ; intravenous, 10 mg kg -1 ). The systemic exposures to Res conjugates were much higher than those to Res (AUC 0-t , i.v., 7.43 μm h; p.o., 8.31 μm h); Res-3-O-β-d-glucuronide was the major metabolite (AUC 0-t , i.v., 66.1 μm h; p.o., 333.4 μm h). The bioavailability of Res was estimated to be ~22.4%. The reproducible SALLE method simplified the sample preparation, drastically improved the accuracy of the concomitant assay and gave full consideration of extraction recovery to each target analyte in bio-samples. Copyright © 2017 John Wiley & Sons, Ltd.

  2. An Optimized and Sensitive Pharmacokinetic Quantitative Method of Investigating Gastrodin, Parishin, and Parishin B, C and E in Beagle Dog Plasma using LC-MS/MS after Intragastric Administration of Tall Gastrodia Capsules

    Directory of Open Access Journals (Sweden)

    Junqiu Liu

    2017-11-01

    Full Text Available Gastrodia elata Blume, called Tianma in China, has been widely used to treat headaches, convulsions and epilepsy for thousands of years. In the present study, a series of optimizations were employed to develop a rapid, sensitive, and reliable high-performance liquid chromatography-triple quadrupole mass spectrometry method, which was then used for the simultaneous determination of gastrodin, parishin, parishin B, parishin C and parishin E in beagle dog plasma after intragastric administration of tall Gastrodia capsules (Tianma brand. The chromatographic separation was achieved on a C18 column with gradient elution by using a mixture of 0.4% formic acid aqueous solution and acetonitrile as the mobile phase at a flow rate of 0.15 mL/min. A tandem mass spectrometric detection was conducted using multiple-reaction monitoring (MRM via electrospray ionization (ESI source in negative ionization mode. Samples were pre-treated by a single-step protein precipitation with methanol, and bergenin was used as internal standard (IS. Under the optimized conditions, the lower limit of quantification (LLOQ was 0.10 ng/mL for gastrodin, 0.40 ng/mL for parishin B, 0.02 ng/mL for parishin E and 0.20 ng/mL for parishin and parishin C, all of which previously were the highest levels of sensitivity. The methods were optimized for selectivity, calibration curves, accuracy and precision. Extraction recoveries, matrix effects and stability were within acceptable ranges. Pharmacokinetic parameters of the tested substances were also quantitatively determined. Finally, a possible metabolic pathway was induced based on correlations obtained from quantitative and qualitative data analysis in vivo.

  3. [Impact of ECMO on drugs pharmacokinetics].

    Science.gov (United States)

    Hasni, Nesrine; Lemaitre, Florian; Fernandez, Christine; Combes, Alain; Farinotti, Robert

    2011-01-01

    Extracorporeal membrane oxygenation (ECMO) is a life support system used in the treatment of patients of all ages with severe respiratory or cardiorespiratory failure. Despite the intensive use of drugs in the treatment of patients on ECMO, few studies have been conducted to determine the impact of this device on the pharmacokinetics of drugs. Publications in this field have shown pharmacokinetics changes resulting in an increase in volume of distribution of drugs and/or decreased clearance with consequent increase of their half-life. Reduced plasma concentrations of some drugs due to their adsorption on the different components of the circuit further complicates the determination of pharmacokinetic parameters of patients treated by ECMO. The literature published up to now on the pharmacokinetic changes associated with ECMO provide preliminary support for dosage adjustment. However, more research is needed to identify dosage strategies for this patient population. © 2011 Société Française de Pharmacologie et de Thérapeutique.

  4. Pharmacokinetics of thiamphenicol in dogs.

    Science.gov (United States)

    Castells, G; Intorre, L; Franquelo, C; Cristòfol, C; Pérez, B; Martí, G; Arboix, M

    1998-11-01

    To determine pharmacokinetic parameters of thiamphenicol (TAP) after IV and IM administration in dogs. 6 healthy 2- to 3-year-old male Beagles. IN a crossover design study, 3 dogs were given TAP IV, and 3 dogs were given TAP IM, each at a dosage of 40 mg/kg of body weight. Three weeks later, the same dogs were given a second dose by the opposite route. At preestablished times after TAP administration, blood samples were collected through a catheter placed in the cephalic vein, and TAP concentration was determined by use of a high-performance liquid chromatography. Results-Kinetics of TAP administered IV were fitted by a biexponential equation with a rapid first disposition phase followed by a slower disposition phase. Elimination half-life was short (1.7+/-0.3 hours), volume of distribution at steady state was 0.66+/-0.05 L/kg, and plasma clearance was 5.3+/-0.7 ml/min/kg. After IM administration, absorption was rapid. Peak plasma concentration (25.1+/-10.3 microg/ml) was reached about 45 minutes after drug administration. The apparent elimination half-life after IM administration (5.6+/-4.6 hours) was longer than that after IV administration probably because of the slow absorption rate from the muscle. Mean bioavailability after IM administration was 96+/-7%. The pharmacokinetic profile of TAP in dogs suggests that it may be therapeutically useful against susceptible microorganisms involved in the most common infections in dogs, such as tracheobronchitis, enterocolitis, mastitis, and urinary tract infections.

  5. Investigating pulmonary and systemic pharmacokinetics of inhaled olodaterol in healthy volunteers using a population pharmacokinetic approach.

    Science.gov (United States)

    Borghardt, Jens Markus; Weber, Benjamin; Staab, Alexander; Kunz, Christina; Formella, Stephan; Kloft, Charlotte

    2016-03-01

    Olodaterol, a novel β2-adrenergic receptor agonist, is a long-acting, once-daily inhaled bronchodilator approved for the treatment of chronic obstructive pulmonary disease. The aim of the present study was to describe the plasma and urine pharmacokinetics of olodaterol after intravenous administration and oral inhalation in healthy volunteers by population pharmacokinetic modelling and thereby to infer its pulmonary fate. Plasma and urine data after intravenous administration (0.5-25 μg) and oral inhalation (2.5-70 μg via the Respimat® inhaler) were available from a total of 148 healthy volunteers (single and multiple dosing). A stepwise model building approach was applied, using population pharmacokinetic modelling. Systemic disposition parameters were fixed to estimates obtained from intravenous data when modelling data after inhalation. A pharmacokinetic model, including three depot compartments with associated parallel first-order absorption processes (pulmonary model) on top of a four-compartment body model (systemic disposition model), was found to describe the data the best. The dose reaching the lung (pulmonary bioavailable fraction) was estimated to be 49.4% [95% confidence interval (CI) 46.1, 52.7%] of the dose released from the device. A large proportion of the pulmonary bioavailable fraction [70.1% (95% CI 66.8, 73.3%)] was absorbed with a half-life of 21.8 h (95% CI 19.7, 24.4 h). The plasma and urine pharmacokinetics of olodaterol after intravenous administration and oral inhalation in healthy volunteers were adequately described. The key finding was that a high proportion of the pulmonary bioavailable fraction had an extended pulmonary residence time. This finding was not expected based on the physicochemical properties of olodaterol. © 2015 The British Pharmacological Society.

  6. Plasma pharmacokinetics, faecal excretion and efficacy of pyrantel pamoate paste and granule formulations following per os administration in donkeys naturally infected with intestinal strongylidae.

    Science.gov (United States)

    Gokbulut, Cengiz; Aksit, Dilek; Smaldone, Giorgio; Mariani, Ugo; Veneziano, Vincenzo

    2014-09-15

    The plasma disposition, faecal excretion and efficacy of two formulations of pyrantel pamoate in donkeys were examined in a controlled trial. Three groups of seven donkeys received either no medication (control) or pyrantel paste or granule formulations at horse dosage of 20mg/kg B.W. (equals 6.94 mg/kg PYR base) of body weight. Heparinized blood and faecal samples were collected at various times between 1 and 144 h after treatment. The samples were analysed by high-performance liquid chromatography. The last detectable plasma concentration (tmax) of paste formulation was significantly earlier (36.00 h) compared with granule formulation (46.29 h). Although, there was no significant difference on terminal half lives (t1/2: 12.39 h vs. 14.86 h), tmax (14.86 h vs. 14.00) and MRT (24.80 h vs. 25.44 h) values; the Cmax (0.09 μg/ml) AUC (2.65 μgh/ml) values of paste formulation were significantly lower and smaller compared with those of granule formulation (0.21 μg/ml and 5.60 μgh/ml), respectively. The highest dry faecal concentrations were 710.46 μg/g and 537.21 μg/g and were determined at 48 h for both paste and granule formulation of PYR in donkeys, respectively. Pre-treatment EPG of 1104, 1061 and 1139 were observed for the control, PYR paste and PYR granule groups, respectively. Pre-treatment EPG were not significantly different (P>0.1) between groups. Post-treatment EPG for both PYR treatment groups were significantly different (P95% efficacy) until day 28. In all studied donkeys, coprocultures performed at day-3 revealed the presence of Cyathostomes, S. vulgaris. Faecal cultures performed on different days from C-group confirmed the presence of the same genera. Coprocultures from treated animals revealed the presence of few larvae of Cyathostomes. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Textbook of dosimetry. 4. ed.

    International Nuclear Information System (INIS)

    Ivanov, V.I.

    1999-01-01

    This textbook of dosimetry is devoted to the students in physics and technical physics of high education institutions, confronted with different application of atomic energy as well as with protection of population and environment against ionizing radiations. Atomic energy is highly beneficial for man but unfortunately incorporates potential dangers which manifest in accidents, the source of which is either insufficient training of the personnel, a criminal negligence or insufficient reliability of the nuclear facilities. The majority of the incident and accident events have had as origin the personnel errors. This was the case with both the 'Three Miles Island' (1979) and Chernobyl (1986) NPP accidents. The dosimetry science acquires a vital significance in accident situations since the data obtained by its procedures are essential in choosing the correct immediate actions, behaviour tactics, orientation of liquidation of accident consequences as well as in ensuring the health of population. An important accent is placed in this manual on clarification of the nature of physical processes taken place in dosimetric detectors, in establishing the relation between radiation field characteristics and the detector response as well as in defining different dosimetric quantities. The terminology and the units of physical quantities is based on the international system of units. The book contains the following 15 chapters: 1. Ionizing radiation field; 2. Radiation doses; 3. Physical bases of gamma radiation dosimetry; 4. Ionization dosimetric detectors; 5. Semiconductor dosimetric detectors; 6. Scintillation detection in the gamma radiation dosimetry; 7. Luminescent methods in dosimetry; 8. The photographic and chemical methods of gamma radiation dosimetry; 9. Neutron dosimetry; 10. Dosimetry of high intensity radiation; 11. Dosimetry of high energy Bremsstrahlung; 12. Measurement of the linear energy transfer; 13. Microdosimetry; 14. Dosimetry of incorporated

  8. Development and Validation of an HPLC Method for Simultaneous Quantification of Clopidogrel Bisulfate, Its Carboxylic Acid Metabolite, and Atorvastatin in Human Plasma: Application to a Pharmacokinetic Study

    Directory of Open Access Journals (Sweden)

    Octavian Croitoru

    2015-01-01

    Full Text Available A simple, sensitive, and specific reversed phase liquid chromatographic method was developed and validated for simultaneous quantification of clopidogrel, its carboxylic acid metabolite, and atorvastatin in human serum. Plasma samples were deproteinized with acetonitrile and ibuprofen was chosen as internal standard. Chromatographic separation was performed on an BDS Hypersil C18 column (250 × 4.6 mm; 5 μm via gradient elution with mobile phase consisting of 10 mM phosphoric acid (sodium buffer solution (pH = 2.6 adjusted with 85% orthophosphoric acid : acetonitrile : methanol with flow rate of 1 mL·min−1. Detection was achieved with PDA detector at 220 nm. The method was validated in terms of linearity, sensitivity, precision, accuracy, limit of quantification, and stability tests. Calibration curves of the analytes were found to be linear in the range of 0.008–2 μg·mL−1 for clopidogrel, 0.01–4 μg·mL−1 for its carboxylic acid metabolite, and 0.005–2.5 μg·mL−1 for atorvastatin. The results of accuracy (as recovery with ibuprofen as internal standard were in the range of 96–98% for clopidogrel, 94–98% for its carboxylic acid metabolite, and 90–99% for atorvastatin, respectively.

  9. Ultra-high-performance liquid chromatography tandem mass spectrometry method for the determination of gambogenic acid in dog plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Chen, Jin Pei; Wang, Dian Lei; Yang, Li Li; Wang, Chen Yin; Wang, Shan Shan

    2014-12-01

    A highly sensitive and rapid ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of gambogenic acid in dog plasma. Gambogic acid was used as an internal standard (IS). After a simple liquid-liquid extraction by ethyl acetate, the analyte and internal standard were separated on an Acquity BEH C18 (100 × 2.1 mm, 1.7 µm; Waters ) column at a flow rate of 0.2 mL/min, using 0.1% formic acid-methanol (10:90, v/v) as mobile phase. Electrospray ionization source was applied and operated in the positive ion mode. Multiple reaction monitoring mode with the transitions m/z 631.3 → 507.3 and m/z 629.1 → 573.2 was used to quantify gambogenic acid and the internal standard, respectively. The calibration curves were linear in the range of 5-1000 ng/mL, with a coefficient of determination (r) of 0.999 and good calculated accuracy and precision. The low limit of quantification was 5 ng/mL. The intra-and inter-day precisions (relative standard deviations) were dogs at a dose of 1 mg/kg. Copyright © 2014 John Wiley & Sons, Ltd.

  10. UNCERTAINTIES IN TRICHLOROETHYLENE PHARMACOKINETIC MODELS

    Science.gov (United States)

    Understanding the pharmacokinetics of a chemical¯its absorption, distribution, metabolism, and excretion in humans and laboratory animals ¯ is critical to the assessment of its human health risks. For trichloroethylene (TCE), numerous physiologically-based pharmacokinetic (PBPK)...

  11. Internal emitter dosimetry: are patient-specific calculations necessary?

    International Nuclear Information System (INIS)

    Sgouros, G.

    1996-01-01

    Full text: The question of whether patient-specific calculations are needed in internal emitter dosimetry arises when radionuclides are used for therapy. In diagnostic procedures the absorbed dose delivered to normal tissue is far below hazardous levels. In internal emitter therapy, the need for patient-specific dosimetry may arise if a large variability in biodistribution, normal tissue toxicity or efficacy is anticipated. Patient-specificity may be accomplished at the level of pharmacokinetics, anatomy/tumor-geometry or both. At the first level, information regarding the biodistribution of a particular radiolabeled agent is obtained and used to determine the maximum activity that may be administered for treatment. The classical example of this is radioiodine therapy for thyroid cancer. In radioiodine therapy, the therapy dose is preceded by a tracer dose of I-131-iodide which is used to measure patient kinetics by imaging and whole-body counting. Absorbed dose estimates obtained from these data are used to constrain the therapy dose to meet safety criteria established in a previously performed dose-response study. The most ambitious approach to patient-specific dosimetry, requires a three-dimensional set of images representing radionuclide distribution (SPECT or PET) and a corresponding set of registered images representing anatomy (CT or MRI). The spatial distribution of absorbed dose or dose-rate may then be obtained by convolution of a point-kernel with the radioactivity distribution or by Monte Carlo calculation. The spatial absorbed dose or dose-rate distribution may be represented as a set of images, as isodose contours, or as dose-volume histograms. The 3-D Monte Carlo approach is, in principle, the most patient-specific; it accounts for patient anatomy and tumor geometry as well as for the spatial distribution of radioactivity. It is also, however, the most logistically and technically demanding. Patients are required to undergo CT or MRI and at least one

  12. Secondary standard dosimetry laboratory at INFLPR

    Energy Technology Data Exchange (ETDEWEB)

    Scarlat, F.; Minea, R.; Scarisoreanu, A.; Badita, E.; Sima, E.; Dumitrascu, M.; Stancu, E.; Vancea, C., E-mail: scarlat.f@gmail.com [National Institute for Laser, Plasma and Radiation Physics - INFLPR, Bucharest (Romania)

    2011-07-01

    National Institute for Laser, Plasma and Radiation Physics (INFLPR) has constructed a High Energy Secondary Standard Dosimetry Laboratory SSDL-STARDOOR - for performing dosimetric calibrations according to ISO IEC SR/EN 17025:2005 standards. This is outfitted with UNIDOS Secondary Standard Dosimeter from PTW (Freiburg Physikalisch-Technische Werksttaten) calibrated at the PTB-Braunschweig (German Federal Institute of Physics and Metrology). A radiation beam of the quality of Q used by our laboratory as calibration source are provided by INFLPR 7 MeV electron beam linear accelerator mounted in our facility. (author)

  13. Enantioselective pharmacokinetics of sibutramine in rat.

    Science.gov (United States)

    Noh, Keumhan; Bae, Kyoungjin; Min, Bokyoung; Kim, Eunyoung; Kwon, Kwang-il; Jeong, Taecheon; Kang, Wonku

    2010-02-01

    Racemic sibutramine is widely used to treat obesity owing to its inhibition of serotonin and noradrenaline reuptake in synapses. Although the enantioselective effects of sibutramine and its two active desmethyl-metabolites, monodesmethylsibutramine (MDS) and didesmethylsibutramine (DDS), on anorexia and energy expenditure have been elucidated, the enantioselective pharmacokinetics of sibutramine are still unclear. Therefore, we aimed to characterize the enantioselective pharmacokinetics of sibutramine and its metabolites in plasma and urine following an intravenous and a single oral administration of sibutramine in rats. The absolute bioavailability of sibutramine was only about 7%. The pharmacologically less effective S-isomer of DDS was predominant in the plasma: the C ( max ) and the AUC ( inf ) were 28 and 30 times higher than those of the R-isomer, respectively (psibutramine metabolites MDS and DDS were present at lower concentrations, owing to their rapid biotransformation to hydroxylated and/or carbamoylglucuronized forms and their faster excretion in the urine. The present study is the first to elucidate the enantioselective pharmacokinetics of sibutramine in rats.

  14. Pharmacokinetics of enterolignans in healthy men and women consuming a single dose of secoisolariciresinol diglucoside

    NARCIS (Netherlands)

    Kuijsten, A.; Arts, I.C.W.; Vree, T.B.; Hollman, P.C.H.

    2005-01-01

    High concentrations of enterolignans in plasma are associated with a lower risk of acute coronary events. However, little is known about the absorption and excretion of enterolignans. The pharmacokinetic parameters and urinary excretion of enterodiol and enterolactone were evaluated after

  15. Modern methods of personnel dosimetry

    International Nuclear Information System (INIS)

    Kraus, W.; Herrmann, D.; Kiesewetter, W.

    The physical properties of radiation detectors for personnel dosimetry are described and compared. The suitability of different types of dosimeters for operational and central monitoring of normal occupational exposure, for accident and catastrophe dosimetry and for background and space-flight dosimetry is discussed. The difficulties in interpreting the dosimeter reading with respect to the dose in individual body organs are discussed briefly. 430 literature citations (up to Spring 1966) are given

  16. The dosimetry of ionizing radiation

    CERN Document Server

    1990-01-01

    A continuation of the treatise The Dosimetry of Ionizing Radiation, Volume III builds upon the foundations of Volumes I and II and the tradition of the preceeding treatise Radiation Dosimetry. Volume III contains three comprehensive chapters on the applications of radiation dosimetry in particular research and medical settings, a chapter on unique and useful detectors, and two chapters on Monte Carlo techniques and their applications.

  17. Comparative pharmacokinetic profiles of selected irreversible tyrosine kinase inhibitors, neratinib and pelitinib, with apigenin in rat plasma by UPLC-MS/MS.

    Science.gov (United States)

    Maher, Hadir M; Alzoman, Nourah Z; Shehata, Shereen M; Abahussain, Ashwag O

    2017-04-15

    Neratinib (NER) and pelitinib (PEL) are irreversible tyrosine kinase inhibitors (TKIs) that have been recently employed in cancer treatment. Apigenin (API), among other flavonoids, is known to have antioxidant, anti-proliferative, and carcinogenic effect. API can potentiate the antitumor effect of chemotherapeutic agents and/or alleviate the side effects of many anticancer agents. Since TKIs are mostly metabolized by CYP3A4 enzymes and that API could alter the enzymatic activity, potential drug interactions could be expected following their co-aministration. In the present study, a bioanalytical UPLC-MS/MS method has been developed and validated for the quantification of NER and PEL in rat plasma, using domperidone (DOM) as an internal standard. Sample preparation was carried out using solid phase extraction (SPE) with C18 cartridges with good extraction recovery of not less than 92.42% (NER) and 89.73% (PEL). Chromatographic analysis was performed on a Waters BEH C18 column with a mobile phase composed of acetonitrile and water, (70:30, v/v), each with 0.1% formic acid. Quantitation was performed using multiple reaction monitoring (MRM) of the transitions from protonated precursor ions [M+H] + , at m/z 557.30 (NER), m/z 468.21 (PEL), and at m/z 426.27 (DOM), to selected product ions at m/z 112.05 (NER), m/z 395.22 (PEL), and at m/z 175.18 (DOM). The method was fully validated as per the FDA guidelines over the concentration range of 0.5-200ng/mL with very low lower limit of quantification (LLOQ) of 0.5ng/mL for both NER and PEL. The intra- and inter-day assay precision and accuracy were evaluated for both drugs and the calculated values of percentage relative standards deviations (%RSD) and relative errors (%E r ) were within the acceptable limits (<15%) for concentrations other than LLOQ and 20% for LLOQ. The applicability of the method was extended to study the possibility of drug interactions following the oral co-administration of NER/PEL with API. Thus, this

  18. Interlaboratory niobium dosimetry comparison

    International Nuclear Information System (INIS)

    Wille, P.

    1980-01-01

    For an interlaboratory comparison of neutron dosimetry using niobium the 93 sup(m)Nb activities of irradiated niobium monitors were measured. This work was performed to compare the applied techniques of dosimetry with Nb in different laboratories. The niobium monitors were irradiated in the fast breeder EBRII, USA and the BR2, Belgium. The monitors were dissolved and several samples were prepared. Their niobium contents were determined by the 94 Nb-count rates. since the original specific count rate was known. The KX radiations of the 93 sup(m)Nb of the samples and of a calibrated Nb-foil were compared. This foil was measured by PTB, Braunschweig and CBNM, Geel, which we additionally compared with the KX radiation of 88 Sr produced by a thin 88 Y source from a 88 Y-standard solution (PTB). (orig.) [de

  19. Neutron beam measurement dosimetry

    International Nuclear Information System (INIS)

    Amaro, C.R.

    1995-01-01

    This report describes animal dosimetry studies and phantom measurements. During 1994, 12 dogs were irradiated at BMRR as part of a 4 fraction dose tolerance study. The animals were first infused with BSH and irradiated daily for 4 consecutive days. BNL irradiated 2 beagles as part of their dose tolerance study using BPA fructose. In addition, a dog at WSU was irradiated at BMRR after an infusion of BPA fructose. During 1994, the INEL BNCT dosimetry team measured neutron flux and gamma dose profiles in two phantoms exposed to the epithermal neutron beam at the BMRR. These measurements were performed as a preparatory step to the commencement of human clinical trials in progress at the BMRR

  20. Hanford External Dosimetry Program

    International Nuclear Information System (INIS)

    Fix, J.J.

    1990-10-01

    This document describes the Hanford External Dosimetry Program as it is administered by Pacific Northwest Laboratory (PNL) in support of the US Department of Energy (DOE) and its Hanford contractors. Program services include administrating the Hanford personnel dosimeter processing program and ensuring that the related dosimeter data accurately reflect occupational dose received by Hanford personnel or visitors. Specific chapters of this report deal with the following subjects: personnel dosimetry organizations at Hanford and the associated DOE and contractor exposure guidelines; types, characteristics, and procurement of personnel dosimeters used at Hanford; personnel dosimeter identification, acceptance testing, accountability, and exchange; dosimeter processing and data recording practices; standard sources, calibration factors, and calibration processes (including algorithms) used for calibrating Hanford personnel dosimeters; system operating parameters required for assurance of dosimeter processing quality control; special dose evaluation methods applied for individuals under abnormal circumstances (i.e., lost results, etc.); and methods for evaluating personnel doses from nuclear accidents. 1 ref., 14 figs., 5 tabs

  1. Thermo-luminescent dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Reither, M; Schorn, B; Schneider, E

    1981-01-01

    The development of paediatric radiology which began in the late 195O's has been characterised by the need to limit the dose of ionising radiation to which the child is subjected. The aim has been to keep radiation exposure as low as possible by the introduction of suitable techniques and by the development of new methods. It is therefore surprising that studies in dosimetry in the paediaytric age range have only been carried out in recent years. One reason for this may have been the fact that a suitable technique of measurement was not available at the time. The introduction of solid state dosimetry based on thermo-luminescence, first into radiotherapy (1968) and subsequently into radiodiagnosis, has made it possible to abandon the previously widely used ionisation chamber. The purpose of the present paper is to indicate the suitability of this form of dose measurement for paediatric radiological purposes and to stimulate its application in this field.

  2. Legal aspects of dosimetry

    International Nuclear Information System (INIS)

    Pomarola, H.

    1976-01-01

    The use of ionizing radiations is regulated in France in all fields of application. The main principles governing inspection activities in the food industry are outlined. Conventional preservation methods are mentioned, after which a discussion is devoted to the preservation of food products by irradiation treatment and the increasing importance given to this technique. Consumer protection automatically implies the obligatory use of dosimetry by inspection organisms if the irradiated merchandise is likely to serve for human or animal consumption. Irradiation treatment permits are granted in a context of specific statutory texts mentioned here. Supervision is constant, but always both realistic and flexible. Each aspect of this treatment is discussed in maximum detail if not quite exhaustively, with special emphasis on dosimetry as an indispensable safety factor [fr

  3. WIPP radiation dosimetry program

    International Nuclear Information System (INIS)

    Wu, C.F.

    1991-01-01

    Radiation dosimetry is the process by which various measurement results and procedures are applied to quantify the radiation exposure of an individual. Accurate and precise determination of radiation dose is a key factor to the success of a radiation protection program. The Waste Isolation Pilot Plant (WIPP), a Department of Energy (DOE) facility designed for permanent repository of transuranic wastes in a 2000-foot-thick salt bed 2150 feet underground, has established a dosimetry program developed to meet the requirements of DOE Order 5480.11, ''Radiation Protection for Occupational Workers''; ANSI/ASME NQA-1, ''Quality Assurance Program Requirements for Nuclear Facilities''; DOE Order 5484.1, ''Environmental Protection, Safety, and Health Protection Information Reporting Requirements''; and other applicable regulations

  4. Quantitative imaging for clinical dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Bardies, Manuel [INSERM U601, 9 Quai Moncousu, 44093 Nantes (France)]. E-mail: manu@nantes.inserm.fr; Flux, Glenn [Department of Physics, Royal Marsden NHS Trust, Sutton (United Kingdom); Lassmann, Michael [Department of Nuclear Medicine, Julis-Maximilians University, Wuerzburg (Germany); Monsieurs, Myriam [Department of Health Physics, University of Ghent, 9000 Ghent (Belgium); Savolainen, Sauli [Department of Physical Sciences, University of Helsinki and HUS, Helsinki Medical Imaging Center, Helsinki University Central Hospital (Finland); Strand, Sven-Erik [Medical Radiation Physics, Department of Clinical Sciences Lund, Lund University (Sweden)

    2006-12-20

    Patient-specific dosimetry in nuclear medicine is now a legal requirement in many countries throughout the EU for targeted radionuclide therapy (TRT) applications. In order to achieve that goal, an increased level of accuracy in dosimetry procedures is needed. Current research in nuclear medicine dosimetry should not only aim at developing new methods to assess the delivered radiation absorbed dose at the patient level, but also to ensure that the proposed methods can be put into practice in a sufficient number of institutions. A unified dosimetry methodology is required for making clinical outcome comparisons possible.

  5. Sixth symposium on neutron dosimetry

    International Nuclear Information System (INIS)

    1987-01-01

    This booklet contains all abstracts of papers presented in 13 sessions. Main topics: Cross sections and Kerma factors; analytical radiobiology; detectors for personnel monitoring; secondary charged particles and microdosimetric basis of q-value for neutrons; personnel dosimetry; concepts for radiation protection; ambient monitoring; TEPC and ion chambers in radiation protection; beam dosimetry; track detectors (CR-39); dosimetry at biomedical irradiation facilities; health physics at therapy facilities; calibration for radiation protection; devices for beam dosimetry (TLD and miscellaneous); therapy and biomedical irradiation facilities; treatment planning. (HP)

  6. Dosimetry for Crystals Irradiation

    CERN Document Server

    Lecomte, Pierre

    2005-01-01

    Before shipment to CMS, all PbWO4 crystals produced in China are irradiated there with 60 Co , in order to insure that the induced absorption coefficient is within specifications. Acceptance tests at CERNand at ENEA also include irradiation with gamma rays from 60 Co sources. There were initially discrepancies in quoted doses and doserates as well as in induced absorption coefficients. The present work resolves the discrepancies in irradiation measurements and defines common dosimetry methods for consistency checks between irradiation facilities.

  7. INDIVIDUAL DOSIMETRY SERVICE

    CERN Multimedia

    1999-01-01

    Personnel in the distribution groups Aleph, Delphi, L3, Opal who also work for other experiments than at LEP, should contact the Individual Dosimetry ServiceWe inform all staff and users under regular dosimetric control that the dosimeters for the monitoring period JANUARY/FEBRUARY will be available from their usual dispatchers on Monday the third of January 2000.Please have your films changed:before the 12 January.The colour of the dosimeter valid in JANUARY/FEBRUARY is WHITE.

  8. INDIVIDUAL DOSIMETRY SERVICE

    CERN Multimedia

    2000-01-01

    Personnel in the distribution groups Aleph, Delphi, L3, Opal who also work for other experiments than at LEP, should contact the Individual Dosimetry Service.We inform all staff and users under regular dosimetric control that the dosimeters for the monitoring period MARCH/APRIL will be available from their usual dispatchers on the third of March 2000.Please have your films changed before the 13th of March.The colour of the dosimeter valid in MARCH/APRIL is BLUE.

  9. Personal radon daughter dosimetry

    International Nuclear Information System (INIS)

    Stocker, H.

    1979-12-01

    The conventional means of radon daughter exposure estimatikn for uranium miners in Canada is by grab sampling and time weighting. Personal dosimetry is a possible alternative method with its own advantages and limitations. The author poses basic questions with regard to two methods of radon daughter detection, thermoluminescent chips and track-etch film. An historical review of previous and current research and development programs in Canada and in other countries is presented, as are brief results and conclusions of each dosimeter evaluation

  10. Personnel radiation dosimetry

    International Nuclear Information System (INIS)

    1987-01-01

    The book contains the 21 technical papers presented at the Technical Committee Meeting to Elaborate Procedures and Data for the Intercomparison of Personnel Dosimeters organizaed by the IAEA on 22-26 April 1985. A separate abstract was prepared for each of these papers. A list of areas in which additional research and development work is needed and recommendations for an IAEA-sponsored intercomparison program on personnel dosimetry is also included

  11. Radiochromic film dosimetry

    International Nuclear Information System (INIS)

    Soares, Christopher G.

    2006-01-01

    The object of this paper is to give a new user some practical information on the use of radiochromic films for medical applications. While various aspects of radiochromic film dosimetry for medical applications have been covered in some detail in several other excellent review articles which have appeared in the last few years [Niroomand-Rad, A., Blackwell, C.R., Coursey, B.M., Gall, K.P., McLaughlin, W.L., Meigooni, A.S., Nath, R., Rodgers, J.E., Soares, C.G., 1998. Radiochromic dosimetry: recommendations of the AAPM Radiation Therapy Committee Task Group 55. Med. Phys. 25, 2093-2115; Dempsey, J.F., Low, D.A., Mutic, S., Markman, J., Kirov, A.S., Nussbaum, G.H., Williamson, J.F., 2000. Validation of a precision radiochromic film dosimetry system for quantitative two-dimensional imaging of acute exposure dose distributions. Med. Phys. 27, 2462-2475; Butson, M.J., Yu, P.K.N., Cheung, T., Metcalfe, P., 2003. Radiochromic film for medical radiation dosimetry. Mater. Sci. Eng. R41, 61-120], it is the intent of the present author to present material from a more user-oriented and practical standpoint. That is, how the films work will be stressed much less than how to make the films work well. The strength of radiochromic films is most evident in applications where there is a very high dose gradient and relatively high absorbed dose rates. These conditions are associated with brachytherapy applications, measurement of small fields, and at the edges (penumbra regions) of larger fields

  12. Tubocurarine and pancuronium: a pharmacokinetic view.

    Science.gov (United States)

    Shanks, C A; Somogyi, A A; Ramzan, M I; Triggs, E J

    1980-02-01

    This review is an attempt to bring together the pharmacokinetic data on d-tubocurarine and pancuronium with clinical observations on relaxant dosage and effect. The modelling techniques used here represent an oversimplification of the relationships between relaxant plasma concentration and response as they do not predict either the time of onset of paralysis or its peak intensity. However, they do enable calculation of a bolus dose of relaxant required to achieve a particular intensity of paralysis for the average patient once pseudo-distribution equilibrium has been achieved. This has been further extended to predict the cumulation of the relaxants with subsequent dosage in average patients. Suggested regimens incorporating bolus and infusion doses of the relaxants to achieve continuous neuromuscular blockade have been calculated also. Averaged pharmacokinetic parameters derived from patients with renal or hepatic dysfunction have been used to predict the likely duration and intensities of paralysis for the relaxants.

  13. Pharmacokinetics of oral and intravenous melatonin in healthy volunteers

    DEFF Research Database (Denmark)

    Andersen, Lars Peter Holst; Werner, Mads Utke; Rosenkilde, Mette Marie

    2016-01-01

    BACKGROUND: The aim was to investigate the pharmacokinetics of oral and iv melatonin in healthy volunteers. METHODS: The study was performed as a cohort crossover study. The volunteers received either 10 mg oral melatonin or 10 mg intravenous melatonin on two separate study days. Blood samples were...... collected at different time points following oral administration and short iv infusion, respectively. Plasma melatonin concentrations were determined by RIA technique. Pharmacokinetic analyses were performed by "the method of residuals" and compartmental analysis. The pharmacokinetic variables: k a, t 1....../2 absorption, t max, C max, t 1/2 elimination, AUC 0-∞, and bioavailability were determined for oral melatonin. C max, t 1/2 elimination, V d, CL and AUC 0-∞ were determined for intravenous melatonin. RESULTS: Twelve male volunteers completed the study. Baseline melatonin plasma levels did not differ...

  14. Pharmacokinetics of rilmenidine in healthy subjects

    International Nuclear Information System (INIS)

    Genissel, P.; Bromet, N.; Fourtillan, J.B.; Mignot, A.; Albin, H.

    1988-01-01

    Rilmenidine is a novel alpha 2-adrenoceptor agonist, used in the treatment of mild or moderate hypertension at the oral dose of 1 mg once or twice daily. The pharmacokinetic parameters were investigated after single or repeated administration in healthy subjects, using labeled and unlabeled compounds. Rilmenidine was rapidly and extensively absorbed, with an absolute bioavailability factor close to 1 and a maximal plasma concentration achieved within 2 hours. Rilmenidine was not subject to presystemic metabolism. Distribution was independent of the free fraction because rilmenidine was weakly bound to plasma proteins (less than 10%). The volume of distribution was approximately 5 l.kg-1 (315 liters). Elimination was rapid with a total body plasma clearance of approximately 450 ml.min-1 and an elimination half-life of approximately 8 hours. Renal excretion was the major elimination process (two-thirds of the total clearance). Metabolism was very poor, with a renal elimination of rilmenidine as the parent drug (urinary fraction of rilmenidine was about 65% and no metabolite plasma levels were detected). Linear pharmacokinetics were demonstrated for rilmenidine from 0.5 to 2 mg but, at 3 mg, a slight deviation from linearity was observed. In repeated administration, the linear disposition of rilmenidine with dose was confirmed

  15. Pharmacokinetics of procaterol in thoroughbred horses.

    Science.gov (United States)

    Kusano, K; Nomura, M; Toju, K; Ishikawa, Y; Minamijima, Y; Yamashita, S; Nagata, S

    2016-06-01

    Procaterol (PCR) is a beta-2-adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 μg/kg) and oral (2.0 μg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography-mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady-state volume of the distribution was 1.21 ± 0.23 L/kg, and the elimination half-life was 2.85 ± 1.35 h. Heart rate rapidly increased after intravenous administration and gradually decreased thereafter. A strong correlation between heart rate and plasma concentration of PCR was observed. Plasma concentrations of PCR after oral administration were not quantifiable in all horses. Urine concentrations of PCR following intravenous and oral administrations were quantified in all horses until 32 h after administration. Urine PCR concentrations were not significantly different on and after 24 h between intravenous and oral administrations. These results suggest that the bioavailability of orally administrated PCR in horses is very poor, and the drug was eliminated from the body slowly based on urinary concentrations. This report is the first study to demonstrate the pharmacokinetic character of PCR in thoroughbred horses. © 2015 John Wiley & Sons Ltd.

  16. Dosimetry: an ARDENT topic

    CERN Multimedia

    CERN Bulletin

    2012-01-01

    The first annual ARDENT workshop took place in Vienna from 20 to 23 November. The workshop gathered together the Early-Stage Researchers (ESR) and their supervisors, plus other people involved from all the participating institutions.   “The meeting, which was organised with the local support of the Austrian Institute of Technology, was a nice opportunity for the ESRs to get together, meet each other, and present their research plans and some preliminary results of their work,” says Marco Silari, a member of CERN Radiation Protection Group and the scientist in charge of the programme. Two full days were devoted to a training course on radiation dosimetry, delivered by renowned experts. The workshop closed with a half-day visit to the MedAustron facility in Wiener Neustadt. ARDENT (Advanced Radiation Dosimetry European Network Training) is a Marie Curie ITN project funded under EU FP7 with €4 million. The project focuses on radiation dosimetry exploiting se...

  17. Dosimetry in dentistry.

    Science.gov (United States)

    Asha, M L; Chatterjee, Ingita; Patil, Preeti; Naveen, S

    2015-01-01

    The purpose of this paper was to review various dosimeters used in dentistry and the cumulative results of various studies done with various dosimeters. Several relevant PubMed indexed articles from 1999 to 2013 were electronically searched by typing "dosimeters", "dosimeters in dentistry", "properties of dosimeters", "thermoluminescent and optically stimulated dosimeters", "recent advancements in dosimetry in dentistry." The searches were limited to articles in English to prepare a concise review on dental dosimetry. Titles and abstracts were screened, and articles that fulfilled the criteria of use of dosimeters in dental applications were selected for a full-text reading. Article was divided into four groups: (1) Biological effects of radiation, (2) properties of dosimeters, (3) types of dosimeters and (4) results of various studies using different dosimeters. The present review on dosimetry based on various studies done with dosimeters revealed that, with the advent of radiographic technique the effective dose delivered is low. Therefore, selection of radiological technique plays an important role in dental dose delivery.

  18. Dosimetry in life sciences

    International Nuclear Information System (INIS)

    1975-01-01

    The uses of radiation in medicine and biology have grown in scope and diversity to make the Radiological Sciences a significant factor in both research and medical practice. Of critical importance in the applications and development of biomedical and radiological techniques is the precision with which the dose may be determined at all points of interest in the absorbing medium. This has developed as a result of efficacy of investigations in clinical radiation therapy, concern for patient safety and diagnostic accuracy in diagnostic radiology and the advent of clinical trials and research into the use of heavily ionizing radiations in biology and medicine. Since the last IAEA Symposium on Dosimetry Techniques applied to Agriculture, Industry, Biology and Medicine, held in Vienna in 1972, it has become increasingly clear that advances in the techniques and hardware of biomedical dosimetry have been rapid. It is for these reasons that this symposium was organized in a concerted effort to focus on the problems, developments and areas of further research in dosimetry in the Life Sciences. (author)

  19. Dosimetry in life sciences

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1975-06-15

    The uses of radiation in medicine and biology have grown in scope and diversity to make the Radiological Sciences a significant factor in both research and medical practice. Of critical importance in the applications and development of biomedical and radiological techniques is the precision with which the dose may be determined at all points of interest in the absorbing medium. This has developed as a result of efficacy of investigations in clinical radiation therapy, concern for patient safety and diagnostic accuracy in diagnostic radiology and the advent of clinical trials and research into the use of heavily ionizing radiations in biology and medicine. Since the last IAEA Symposium on Dosimetry Techniques applied to Agriculture, Industry, Biology and Medicine, held in Vienna in 1972, it has become increasingly clear that advances in the techniques and hardware of biomedical dosimetry have been rapid. It is for these reasons that this symposium was organized in a concerted effort to focus on the problems, developments and areas of further research in dosimetry in the Life Sciences. (author)

  20. Pharmacokinetics and toxicology of continuously infused nitroimidazoles

    International Nuclear Information System (INIS)

    Eifel, P.J.; Brown, J.M.

    1984-01-01

    The pharmacokinetics and toxicology of misonidazole (MISO) and SR-2508 given by continuous intraperitoneal infusion were studied in female C 3 H mice. The survival (time to death) of animals receiving continuous infusions of SR-2508 and MISO was compared and related to plasma concentration, rate of infusion and total amount of drug delivered. Brain and plasma concentrations were determined by HPLC. For SR-2508, plasma concentration was directly proportional to the infusion rate. However, as the infusion rate of MISO was doubled, the plasma concentration of MISO increased approximately 6-fold, reflecting a substantial increase in the apparent half-life. The brain/plasma concentration ratio in animals infused for up to 6 days with SR-2508 remained constant, at approximately 0.09. At plasma concentrations of 0.08-1.5 mM, animals receiving SR-2508 survived approximately 3 times as long as animals exposed to a comparable plasma concentration of MISO. Even at the lowest infusion rates employed in this study, the survival of mice receiving SR-2508 was much shorter than would have been predicted if the toxicity of these two drugs were solely related to the integral brain exposure. The low brain/plasma concentration ratio of SR-2508 was maintained throughout long continuous exposures

  1. Individual dosimetry and calibration

    International Nuclear Information System (INIS)

    Otto, T.

    1997-01-01

    In 1996, the Dosimetry and Calibration Section was, as in previous years, mainly engaged in routine tasks: the distribution of over 6000 dosimeters (with a total of more than 10,000 films) every two months and the calibration of about 900 fixed and mobile instruments used in the radiation survey sections of RP group. These tasks were, thanks to an experienced team, well mastered. Special efforts had to be made in a number of areas to modernize the service or to keep it in line with new prescriptions. The Individual Dosimetry Service had to assure that CERN's contracting firms comply with the prescriptions in the Radiation Safety Manual (1996) that had been inspired by the Swiss Ordinance of 1994: Companies must file for authorizations with the Swiss Federal Office for Public Health requiring that in every company an 'Expert in Radiation Protection' be nominated and subsequently trained. CERN's Individual Dosimetry Service is accredited by the Swiss Federal Authorities and works closely together with other, similar services on a rigorous quality assurance programme. Within this framework, CERN was mandated to organize this year the annual Swiss 'Intercomparison of Dosimeters'. All ten accredited dosimetry services - among others those of the Paul Scherrer Institute (PSI) in Villigen and of the four Swiss nuclear power stations - sent dosimeters to CERN, where they were irradiated in CERN's calibration facility with precise photon doses. After return to their origin they were processed and evaluated. The results were communicated to CERN and were compared with the originally given doses. A report on the results was subsequently prepared and submitted to the Swiss 'Group of Experts on Personal Dosimetry'. Reference monitors for photon and neutron radiation were brought to standard laboratories to assure the traceability of CERN's calibration service to the fundamental quantities. For photon radiation, a set of ionization chambers was calibrated in the reference field

  2. Advances in biomedical dosimetry

    International Nuclear Information System (INIS)

    1981-01-01

    Full text: Radiation dosimetry, the accurate determination of the absorbed dose within an irradiated body or a piece of material, is a prerequisite for all applications of ionizing radiation. This has been known since the very first radiation applications in medicine and biology, and increasing efforts are being made by radiation researchers to develop more reliable, effective and safe instruments, and to further improve dosimetric accuracy for all types of radiation used. Development of new techniques and instrumentation was particularly fast in the field of both medical diagnostic and therapeutic radiology. Thus, in Paris in October the IAEA held the latest symposium in its continuing series on dosimetry in medicine and biology. The last one was held in Vienna in 1975. High-quality dosimetry is obviously of great importance for human health, whether the objectives lie in the prevention and control of risks associated with the nuclear industry, in medical uses of radioactive substances or X-ray beams for diagnostic purposes, or in the application of photon, electron or neutron beams in radiotherapy. The symposium dealt with the following subjects: General aspects of dosimetry; Special physical and biomedical aspects; Determination of absorbed dose; Standardization and calibration of dosimetric systems; and Development of dosimetric systems. The forty or so papers presented and the discussions that followed them brought out a certain number of dominant themes, among which three deserve particular mention. - The recent generalization of the International System of Units having prompted a fundamental reassessment of the dosimetric quantities to be considered in calibrating measuring instruments, various proposals were advanced by the representatives of national metrology laboratories to replace the quantity 'exposure' (SI unit = coulomb/kg) by 'Kerma' or 'absorbed dose' (unit joule/kg, the special name of which is 'gray'), this latter being closer to the practical

  3. A comparison of the pharmacokinetics of Aspen Ceftriaxone and ...

    African Journals Online (AJOL)

    Medicines Control Council (MCC) requires proof of equivalence ... clinical pharmacokinetics (PK) of a generic ceftriaxone formulation with the originator. .... on performance of the quality control samples). ... Endogenous components of plasma had an insignificant effect .... Clinical features and prognostic factors in adults with.

  4. Clinical pharmacokinetics of nisoldipine coat-core.

    Science.gov (United States)

    Heinig, R

    1998-09-01

    Nisoldipine, a calcium antagonist of the dihydropyridine type, is the active ingredient of the controlled release nisoldipine coat-core (CC) formulation. In humans, the absorption from nisoldipine CC occurs across the entire gastrointestinal tract with an increase in bioavailability in the colon because of the lower concentrations of metabolising enzymes in the distal gut wall. Although nisoldipine is almost completely absorbed, its absolute bioavailability from the CC tablet is only 5.5%, as a result of significant first-pass metabolism in the gut and liver. Nisoldipine is a high-clearance drug with substantial interindividual and relatively lower intraindividual variability in pharmacokinetics, dependent on liver blood flow. Nisoldipine is highly (> 99%) protein bound. Its elimination is almost exclusively via the metabolic route and renal excretion of metabolites dominates over excretion in the faeces. Although nisoldipine is administered as a racemic mixture, its plasma concentrations are almost entirely caused by the eutomer as a result of highly stereoselective intrinsic clearance. Nisoldipine CC demonstrates linear pharmacokinetics in the therapeutic dose range and its steady-state pharmacokinetics are predictable from single dose data. Steady-state is reached with the second dose when the drug is given once daily and the peak-trough fluctuations in plasma concentration is minimal. Plasma-concentrations of nisoldipine increase with age. Careful dose titration according to individual clinical response is recommended in the elderly. Nisoldipine CC should not be used in patients with liver cirrhosis, though dosage adjustments in patients with renal impairment are not necessary. Inter-ethnic differences in its pharmacokinetics are not evident. Owing to inhibition of metabolising enzymes, a small dosage adjustment decrement for nisoldipine CC may be required when it is given in combination with cimetidine. Concomitant ingestion of nisoldipine with grapefruit

  5. Pharmacokinetics of Melatonin

    DEFF Research Database (Denmark)

    Andersen, Lars Peter Holst; Gögenur, Ismail; Rosenberg, Jacob

    2016-01-01

    Despite widespread clinical application of melatonin, several unanswered questions remain regarding the pharmacokinetics of this drug. This lack of knowledge may contribute to the inconsistency of results in previous clinical studies. Currently, a t max value of 30-45 min and a t ½elimination of ...

  6. Pharmacokinetic evaluation of pemetrexed

    DEFF Research Database (Denmark)

    Sørensen, Jens Benn

    2011-01-01

    correlates with renal function and it may be safely used with vitamin supplementation in patients with creatinine clearance ≥ 45 ml/min. The pharmacokinetics of pemetrexed is also largely unchanged in third-space fluids and can be feasibly and safely administered in combination with several other cytotoxic...

  7. Pharmacokinetic evaluation of pemetrexed

    DEFF Research Database (Denmark)

    Sørensen, Jens Benn

    2011-01-01

    correlates with renal function and it may be safely used with vitamin supplementation in patients with creatinine clearance = 45 ml/min. The pharmacokinetics of pemetrexed is also largely unchanged in third-space fluids and can be feasibly and safely administered in combination with several other cytotoxic...

  8. Special workshop on lung dosimetry

    International Nuclear Information System (INIS)

    Fisher, D.R.

    1983-01-01

    A Special Workshop on Lung Dosimetry was convened in Salt Lake City, Utah, on April 21-22, 1982, to stimulate the use of improved radiation dosimetry and to formulate a stronger basis for dose-response relationships for inhaled radionuclides. The two-day workshop was held in conjunction with the 30th Annual Meeting of the Radiation Research Society. Publication is planned

  9. Minocycline pharmacokinetics and pharmacodynamics in dogs

    DEFF Research Database (Denmark)

    Maaland, Marit Gaastra; Guardabassi, Luca; Papich, Mark G.

    2014-01-01

    BACKGROUND: Although minocycline is not licensed for use in dogs, this tetracycline has therapeutic potential against meticillin-resistant Staphylococcus pseudintermedius. HYPOTHESIS/OBJECTIVES: The aim of this study was to establish rational dosage recommendations for minocycline use in dogs....... Specific objectives were to generate and analyse minocycline pharmacokinetic (PK) data on plasma and interstitial fluid (ISF) concentrations, plasma protein binding and pharmacodynamic (PD) data on antimicrobial activity against S. pseudintermedius. ANIMALS: Six healthy dogs from a research colony were...... used in this study. METHODS: Dogs were administered 5 mg/kg intravenously and 10 mg/kg orally (p.o.) of minocycline hydrochloride in separate crossover experiments. In vivo drug concentrations in plasma and in ISF collected by ultrafiltration were measured by high-performance liquid chromatography...

  10. Population pharmacokinetics of olprinone in healthy male volunteers

    Directory of Open Access Journals (Sweden)

    Kunisawa T

    2014-03-01

    Full Text Available Takayuki Kunisawa,1 Hidefumi Kasai,2 Makoto Suda,2 Manabu Yoshimura,3 Ami Sugawara,3 Yuki Izumi,3 Takafumi Iida,3 Atsushi Kurosawa,3 Hiroshi Iwasaki3 1Surgical Operation Department, Asahikawa Medical University Hospital, Hokkaido, Japan; 2Clinical Study Management Division, Bell Medical Solutions Inc, Tokyo, Japan; 3Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan Background: Olprinone decreases the cardiac preload and/or afterload because of its vasodilatory effect and increases myocardial contractility by inhibiting phosphodiesterase III. Purpose: The objective of this study was to characterize the population pharmacokinetics of olprinone after a single continuous infusion in healthy male volunteers. Methods: We used 500 plasma concentration data points collected from nine healthy male volunteers for the study. The population pharmacokinetic analysis was performed using the nonlinear mixed effect model (NONMEM® software. Results: The time course of plasma concentration of olprinone was best described using a two-compartment model. The final pharmacokinetic parameters were total clearance (7.37 mL/minute/kg, distribution volume of the central compartment (134 mL/kg, intercompartmental clearance (7.75 mL/minute/kg, and distribution volume of the peripheral compartment (275 mL/kg. The interindividual variability in the total clearance was 12.4%, and the residual error variability (exponential and additive were 22.2% and 0.129 (standard deviation. The final pharmacokinetic model was assessed using a bootstrap method and visual predictive check. Conclusion: We developed a population pharmacokinetic model of olprinone in healthy male adults. The bootstrap method and visual predictive check showed that this model was appropriate. Our results might be used to develop the population pharmacokinetic model in patients. Keywords: phosphodiesterase III inhibitor, men, pharmacokinetic model

  11. Aqueous chemical dosimetry

    International Nuclear Information System (INIS)

    Matthews, R.W.

    1982-01-01

    Aqueous chemical dosimetry based on ceric and ferrous sulfate solutions and on a number of fluorescence-induced systems is reviewed. Particular attention is given to the factors affecting the response of these dosimeters to radiation and the corrections necessary for more accurate dosimetry under various irradiation conditions. The effect of cerous and ceric ion, oxygen, and sulfuric acid concentration on the ceric dosimeter is discussed together with the effects of temperature, energy of radiation, degraded energy spectra, and peroxysulfuric acids. Practical aspects of ceric/cerous dosimetry are given. Although ferrous sulfate solution is the most important and widely studied reference dosimeter, general agreement has not been reached on the ''best'' value for the molar extinction coefficient of ferric ions nor on the correction necessary to the G(Fe 3 - ) value for irradiations at temperatures significantly different from 25 0 C. New data are presented which indicate that the larger temperature coefficients given in the literature are more accurate. The ferrous sulfate system has been of great importance in establishing the primary radiolytic yields for 0.4 M sulfuric acid solution; it is shown how the failure to take into account the effect of oxygen and ferrous sulfate concentrations has led to erroneously high estimates of the zero solute concentration values in acid solutions. Some of the methods for extending the dose ranges measurable with ferrous sulfate-based solutions are reviewed. Substances which on irradiation give highly fluorescent products are among the most sensitive aqueous chemical dosimeters. These include benzoate and terephthalate solutions and the more recent coumarin and trimesate solutions. Advantages and disadvantages system are discussed. (author)

  12. 醋酸环丙孕酮/炔雌醇复方片剂在人体的药代动力学%Pharmacokinetics of compound cyproterone acetate/ethinylestradiol tablets in human plasma

    Institute of Scientific and Technical Information of China (English)

    谭文明; 丁黎; 张正行; 杨劲

    2014-01-01

    目的 建立人血浆中醋酸环丙孕酮的HPLC-ESI-MS测定方法和丹酰氯衍生化血浆中炔雌醇的HPLC-APCI-MS测定方法,测定女性志愿者口服复方醋酸环丙孕酮片1片后的药代动力学参数,并对受试制剂和参比制剂的生物等效性进行评价.方法 血浆样品中的炔雌醇以乙酸乙酯提取后,与丹酰氯发生衍生化反应,进行HPLC-APCI-MS分析,流动相为10 mmol·L-1乙酸铵缓冲液(1%甲酸)-甲醇(3:97).检测离子分别为m/z 530.3(炔雌醇的丹酰氯衍生物)、m/z 404.3(内标,对羟基联苯的丹酰氯衍生物).结果 在10.43~625.8 pg·ml-1范围内炔雌醇的丹酰氯衍生物与内标的丹酰氯衍生物峰面积比值与浓度呈良好的线性关系,最低定量限为10.43 pg·ml-1.结论 本实验建立的分析方法灵敏、准确、简便,且统计学结果表明两种制剂生物等效.%Objective To develop an HPLC-ESI-MS assay for rapid determination of cyproterone acetate in human plasma and develop an HPLC-APCI-MS assay for determination of ethinylestradiol after derivatization with dansyl chloride and investigate the pharmacokinetics and bioequivalence of two compound cyproterone acetate tablets (containing 2 mg cyproterone acetate and 35 μ g ethinylestradiol) in 20 healthy women volunteers.Methods For ethinylestradiol,after its being extracted with ethyl acetate,the residue was derivatived with dansyl chloride,and separated by HPLC on a reversed-phase C18 column with a mobile phase of 10 mmol · L-1 ammonium acetate buffer solution (1% formic acid)-methanol (3:97).HPLC-APCIMS was performed in the selected ion monitoring (SIM) mode using target ions at m/z 530.3 for 3-dansylethinylestradiol,m/z 404..3 for 4-dansyl-hydroxybiphenyl.Results For ethinylestradiol,calibration curves were linear over the range 10.43-625.8 pg · ml-1,the lower limit of quantification in plasma was 10.43 pg · ml-1.Conclusion The assay is proved to be sensitive,accurate and convenient.The two

  13. Heavy-ion dosimetry

    International Nuclear Information System (INIS)

    Schimmerling, W.

    1980-03-01

    This lecture deals with some of the more important physical characteristics of relativistic heavy ions and their measurement, with beam delivery and beam monitoring, and with conventional radiation dosimetry as used in the operation of the BEVALAC biomedical facility for high energy heavy ions (Lyman and Howard, 1977; BEVALAC, 1977). Even so, many fundamental aspects of the interaction of relativistic heavy ions with matter, including important atomic physics and radiation chemical considerations, are not discussed beyond the reminder that such additional understanding is required before an adequte perspective of the problem can be attained

  14. Individual dosimetry and calibration

    International Nuclear Information System (INIS)

    Hoefert, M.; Nielsen, M.

    1996-01-01

    In 1995 both the Individual Dosimetry and Calibration Sections worked under the condition of a status quo and concentrated fully on the routine part of their work. Nevertheless, the machine for printing the bar code which will be glued onto the film holder and hence identify the people when entering into high radiation areas was put into operation and most of the holders were equipped with the new identification. As far as the Calibration Section is concerned the project of the new source control system that is realized by the Technical Support Section was somewhat accelerated

  15. NRPB patient dosimetry service

    International Nuclear Information System (INIS)

    Shrimpton, P.; Hillier, M.; Bungay, D.; Wall, B.

    1994-01-01

    For nearly 20 years, thermoluminescent dosemeters (TLDs) have been used by NRPB to investigate the doses received by patients undergoing diagnostic examinations with x-rays, and these measurements have formed the basis for national recommendations on patient protection. Monitoring typical levels of patient dose should represent an essential element of routine quality assurance in x-ray departments. In order to promote more widespread measurements in hospitals, NRPB has drawn on a wealth of experience to establish a high-quality service providing TLDs for medical dosimetry by post. (author)

  16. Internal dosimetry and control

    International Nuclear Information System (INIS)

    Rich, B.L.

    1990-05-01

    This internal dosimetry and control report provides guidance for EG ampersand G Idaho, Inc., field programs in detecting, evaluating, and controlling personnel exposure resulting from uptake of radionuclides by the body. Procedures specific to each program or facility are required to define the details of guidance from this report. Fundamental principles related to philosophy, policies, monitoring guidelines, and dose evaluation are discussed. Specific numerical guides and action levels are developed to guide the programs in evaluating the significance of specific analytical results. The requirement to thoroughly document the results and provide a formal technical base for each policy and/or practice is outlined and explained. 8 refs., 3 figs., 7 tabs

  17. Dosimetry in Radiology

    International Nuclear Information System (INIS)

    Andisco, D.; Blanco, S.; Buzzi, A.E

    2014-01-01

    The steady growth in the use of ionizing radiation in diagnostic imaging requires to maintain a proper management of patient’s dose. Dosimetry in Radiology is a difficult topic to address, but vital for proper estimation of the dose the patient is receiving. The awareness that every day is perceived in our country on these issues is the appropriate response to this problem. This article describes the main dosimetric units used and easily exemplifies doses in radiology through internationally known reference values. (authors) [es

  18. INDIVIDUAL DOSIMETRY SERVICE

    CERN Multimedia

    2000-01-01

    Personnel in the distribution groups Aleph, Delphi, L3, Opal who also work for other experiments than at LEP, should contact their dispatchers to explain their activities for the future, after LEP dismantling in order to be maintained on the regular distribution list at Individual Dosimetry ServiceWe inform all staffs and users under regular dosimetric control that the dosimeters for the monitoring period JULY/AUGUST are available from their usual dispatchers.Please have your films changed before the 10th of July.The colour of the dosimeter valid in JULY/AUGUST is PINK.

  19. Fast neutron dosimetry

    International Nuclear Information System (INIS)

    DeLuca, P.M. Jr.; Pearson, D.W.

    1992-01-01

    This progress report concentrates on two major areas of dosimetry research: measurement of fast neutron kerma factors for several elements for monochromatic and white spectrum neutron fields and determination of the response of thermoluminescent phosphors to various ultra-soft X-ray energies and beta-rays. Dr. Zhixin Zhou from the Shanghai Institute of Radiation Medicine, People's Republic of China brought with him special expertise in the fabrication and use of ultra-thin TLD materials. Such materials are not available in the USA. The rather unique properties of these materials were investigated during this grant period

  20. Tritium dosimetry and standardization

    International Nuclear Information System (INIS)

    Balonov, M.I.

    1983-01-01

    Actual problem of radiation hygiene such as an evaluation of human irradiation hazard due to a contact with tritium compounds both in industrial and public spheres is under discussion. Sources of tritium release to environment are characterized. Methods of tritium radiation monitoring are discussed. Methods of dosimetry of internal human exposure resulted from tritium compounds are developed on the base of modern representations on metbolism and tritium radiobiological effect. A system of standardization of permissible intake of tritium compounds for personnel and persons of population is grounded. Some protection measures are proposed as applied to tritium overdosage

  1. Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide in Healthy Subjects.

    Science.gov (United States)

    Dolder, Patrick C; Schmid, Yasmin; Steuer, Andrea E; Kraemer, Thomas; Rentsch, Katharina M; Hammann, Felix; Liechti, Matthias E

    2017-10-01

    Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. The aim of the present study was to characterize the pharmacokinetics and exposure-response relationship of oral LSD. We analyzed pharmacokinetic data from two published placebo-controlled, double-blind, cross-over studies using oral administration of LSD 100 and 200 µg in 24 and 16 subjects, respectively. The pharmacokinetics of the 100-µg dose is shown for the first time and data for the 200-µg dose were reanalyzed and included. Plasma concentrations of LSD, subjective effects, and vital signs were repeatedly assessed. Pharmacokinetic parameters were determined using compartmental modeling. Concentration-effect relationships were described using pharmacokinetic-pharmacodynamic modeling. Geometric mean (95% confidence interval) maximum plasma concentration values of 1.3 (1.2-1.9) and 3.1 (2.6-4.0) ng/mL were reached 1.4 and 1.5 h after administration of 100 and 200 µg LSD, respectively. The plasma half-life was 2.6 h (2.2-3.4 h). The subjective effects lasted (mean ± standard deviation) 8.2 ± 2.1 and 11.6 ± 1.7 h for the 100- and 200-µg LSD doses, respectively. Subjective peak effects were reached 2.8 and 2.5 h after administration of LSD 100 and 200 µg, respectively. A close relationship was observed between the LSD concentration and subjective response within subjects, with moderate counterclockwise hysteresis. Half-maximal effective concentration values were in the range of 1 ng/mL. No correlations were found between plasma LSD concentrations and the effects of LSD across subjects at or near maximum plasma concentration and within dose groups. The present pharmacokinetic data are important for the evaluation of clinical study findings (e.g., functional magnetic resonance imaging studies) and the interpretation of LSD intoxication. Oral LSD presented dose-proportional pharmacokinetics and first-order elimination up to 12 h. The effects of LSD were related

  2. Dosimetry of industrial sources

    International Nuclear Information System (INIS)

    Vega C, H.R.; Rodriguez J, R.; Manzanares A, E.; Hernandez V, R.; Ramirez G, J.; Rivera M, T.

    2007-01-01

    The gamma rays are produced during the disintegration of the atomic nuclei, its high energy allows them to cross thick materials. The capacity to attenuate a photons beam allows to determine the density, in line, of industrial interest materials as the mining. By means of two active dosemeters and a TLDs group (passive dosimetry) the dose rates of two sources of Cs-137 used for determining in line the density of mining materials were determined. With the dosemeters the dose levels in diverse points inside the grave that it harbors the sources and by means of calculations the isodoses curves were determined. In the phase of calculations was supposed that both sources were punctual and the isodose curves were calculated for two situations: naked sources and in their Pb packings. The dosimetry was carried out around two sources of 137 Cs. The measured values allowed to develop a calculation procedure to obtain the isodoses curves in the grave where the sources are installed. (Author)

  3. Clinical dosimetry using mosfets

    International Nuclear Information System (INIS)

    Ramani, Ramaseshan; Russell, Stephen; O'Brien, Peter

    1997-01-01

    Purpose: The use of metal oxide-silicon field effect transistors (MOSFETs) as clinical dosimeters is demonstrated for a number of patients with targets at different clinical sites. Methods and Materials: Commercially available MOSFETs were characterized for energy response, angular dependency of response, and effect of accumulated dose on sensitivity and some inherent properties of MOSFETs. The doses determined both by thermoluminescence dosimetry (TLD) and MOSFETs in clinical situation were evaluated and compared to expected doses determined by calculation. Results: It was observed that a standard calibration of 0.01 Gy/mV gave MOSFET determined doses which agreed with expected doses to within 5% at the 95% confidence limit for photon beams from 6 to 25 MV and electron beams from 5 to 14 MeV. An energy-dependent variation in response of up to 28% was observed between two orientations of a MOSFET. The MOSFET doses compared very well with the doses estimated by TLDs, and the patients tolerated MOSFETs very well. A standard deviation of 3.9% between expected dose and MOSFET determined dose was observed, while for TLDs the standard deviation was 5.1%. The advantages and disadvantages of using MOSFETs for clinical dosimetry are discussed in detail. Conclusion: It was concluded that MOSFETs can be used as clinical dosimeters and can be a good alternative to TLDs. However, they have limitations under certain clinical situations

  4. Information from the Dosimetry Service

    CERN Multimedia

    2006-01-01

    Please note the following opening hours of the Service: From 31st July onwards: Every morning from 8:30 to 12:00 The Service is closed in the afternoons. We should like to remind you that dosimeters cannot be sent to customers by internal mail. Short-term dosimeters (VCTs) must always be returned to the Service after use and must not be left on the racks in the experimental areas or in the secretariats. Dosimetry Service Tel 72155 Bldg. 24 E 011 Dosimetry.service@cern.ch http://cern.ch/rp-dosimetry

  5. Foundations of ionizing radiation dosimetry

    International Nuclear Information System (INIS)

    Denisenko, O.N.; Pereslegin, I.A.

    1985-01-01

    Foundations of dosimetry in application to radiotherapy are presented. General characteristics of ionizing radiations and main characteristics of ionizing radiation sources, mostly used in radiotherapy, are given. Values and units for measuring ionizing radiation (activity of a radioactive substance, absorbed dose, exposure dose, integral dose and dose equivalent are considered. Different methods and instruments for ionizing radiation dosimetry are discussed. The attention is paid to the foundations of clinical dosimetry (representation of anatomo-topographic information, choice of radiation conditions, realization of radiation methods, corrections for a configuration and inhomogeneity of a patient's body, account of biological factors of radiation effects, instruments of dose field formation, control of irradiation procedure chosen)

  6. Techniques for radiation measurements: Micro-dosimetry and dosimetry

    International Nuclear Information System (INIS)

    Waker, A. J.

    2006-01-01

    Experimental Micro-dosimetry is concerned with the determination of radiation quality and how this can be specified in terms of the distribution of energy deposition arising from the interaction of a radiation field with a particular target site. This paper discusses various techniques that have been developed to measure radiation energy deposition over the three orders of magnitude of site-size; nano-meter, micrometer and millimetre, which radiation biology suggests is required to fully account for radiation quality. Inevitably, much of the discussion will concern the use of tissue-equivalent proportional counters and variants of this device, but other technologies that have been studied, or are under development, for their potential in experimental Micro-dosimetry are also covered. Through an examination of some of the quantities used in radiation metrology and dosimetry the natural link with Micro-dosimetric techniques will be shown and the particular benefits of using Micro-dosimetric methods for dosimetry illustrated. (authors)

  7. Skin dosimetry - radiological protection aspects of skin dosimetry

    International Nuclear Information System (INIS)

    Dennis, J.A.

    1991-01-01

    Following a Workshop in Skin Dosimetry, a summary of the radiological protection aspects is given. Aspects discussed include routine skin monitoring and dose limits, the need for careful skin dosimetry in high accidental exposures, techniques for assessing skin dose at all relevant depths and the specification of dose quantities to be measured by personal dosemeters and the appropriate methods to be used in their calibration. (UK)

  8. Pharmacokinetics of high-dose intravenous melatonin in humans

    DEFF Research Database (Denmark)

    Andersen, Lars P H; Werner, Mads U; Rosenkilde, Mette Marie

    2016-01-01

    This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60......, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments...... of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221...

  9. Pharmacokinetics of oral terbinafine in adult horses.

    Science.gov (United States)

    Younkin, T J; Davis, E G; Kukanich, B

    2017-08-01

    The primary study objective was to compare the pharmacokinetics of p.o. terbinafine alone to p.o. terbinafine administered with p.o. cimetidine in healthy adult horses. The second objective was to assess the pharmacokinetics of terbinafine when administered per rectum in two different suspensions at 30 mg/kg to adult horses. Six healthy adult horses were included in this crossover study. Plasma terbinafine concentrations were quantified with liquid chromatography and mass spectrometry. The half-life (geometric mean) was 8.38 and 10.76 h, for p.o. alone and p.o. with cimetidine, respectively. The mean maximum plasma concentrations were 0.291 μg/mL at 1.54 h and 0.418 μg/mL at 1.28 h for p.o. alone and p.o. with cimetidine, respectively. Terbinafine with cimetidine had an average C MAX 44% higher and the relative F was 153% compared p.o. terbinafine alone, but was not statistically different (P > 0.05). Terbinafine was infrequently detected when administered per rectum in two different suspensions (water or olive oil). Minor adverse effects included oral irritation, fever, and colic. All resolved spontaneously. More pharmacokinetic studies are indicated assessing drug-drug interactions and using multiple dosing intervals to improve our knowledge of effective oral dosing, the potential for drug accumulation, and systemic adverse effect of terbinafine in horses. © 2016 John Wiley & Sons Ltd.

  10. Clinical pharmacokinetics of 5-methyltetrahydrohomofolate

    International Nuclear Information System (INIS)

    Loo, T.L.; Jiushi, L.; Lu, K.; Savaraj, N.

    1983-01-01

    DL-N5-Methyltetrahydrohomofolate (MTHHF; NSC-139490; N- [(4-[(2-(2-amino-3,4,5,6,7,8-hexahydro-4-oxo-5-methyl-6- pteridinyl)ethyl) amino) benzoyl)] -L-glutamate), a new folate antagonist of relatively low toxicity, is active against experimental tumor systems resistant to methotrexate and consequently now in clinical trial. We investigated its clinical pharmacokinetics in six patients; four of them received by rapid i.v. infusion tracer doses of [N5-methyl- 14 C]MTHHF ranging from 13 to 16 mg/sq m, and 2 received 150 mg/sq m; the total radioactivity dose was 100 to 200 mu Ci/patient. MTHHF was assayed by radiochemical and chromatographic techniques. The elimination of MTHHF from the plasma followed a triexponential pattern, with a harmonic mean initial half-life of 20.1 min, an intermediary half-life of 4.5 hr, and a terminal half-life of 74.6 hr. The apparent volume of distribution was 1.6 liters/kg, suggesting rapid and extensive tissue binding. This, together with the low total clearance of 0.2 ml/kg/min, contributed to the long half-life of this agent. Although 68% of the administered dose was excreted in the urine on the first day, only an additional 1% was excreted on the ensuing 3 days. In the two patients who received the higher dose, very little MTHHF was found in the cerebrospinal fluid. In concentrations ranging from 25 to 500 micrograms/ml, the drug was about 50% bound to plasma protein. MTHHF was not metabolized in humans as also reported in animals. These results suggest that MTHHF is excreted in the bile to certain extent. Moreover, since it tends to localize and persist in the body, to forestall cumulative toxicity, frequent administration of this agent should be undertaken only with caution

  11. Alanine dosimetry for clinical applications. Proceedings

    International Nuclear Information System (INIS)

    Anton, M.

    2006-05-01

    The following topics are dealt with: Therapy level alanine dosimetry at the UK Nationational Physical Laboratory, alanine as a precision validation tool for reference dosimetry, composition of alanine pellet dosimeters, the angular dependence of the alanine ESR spectrum, the CIAE alanine dosimeter for radiotherapy level, a correction for temporal evolution effects in alanine dosimetry, next-generation services foe e-traceability to ionization radiation national standards, establishing e-traceability to HIST high-dose measurement standards, alanine dosimetry of dose delivery from clinical accelerators, the e-scan alanine dosimeter reader, alanine dosimetry at ISS, verification of the integral delivered dose for IMRT treatment in the head and neck region with ESR/alanine dosimetry, alanine dosimetry in helical tomotherapy beams, ESR dosimetry research and development at the University of Palermo, lithium formate as a low-dose EPR radiation dosimeter, sensitivity enhancement of alanine/EPR dosimetry. (HSI)

  12. Results of the dosimetry intercomparison

    International Nuclear Information System (INIS)

    Dure, Elsa S.

    2000-07-01

    The appropriate way to verify the accuracy of the results of dose reported by the laboratories that offer lend personal dosimetry service is in the periodic participation of round of intercomparison dosimetry, undertaken by laboratories whose standards are trace (Secondary Laboratory). The Laboratory of External Personal Dosimetry of the CNEA-PY has participated in three rounds of intercomparison. The first two were organized in the framework of the Model Project RLA/9/030 RADIOLOGICAL WASTE SECURITY, and the irradiations were carried out in the Laboratory of Regional Calibration of the Center of Nuclear Technology Development, Belo Horizonte-Brazil (1998) and in the National Laboratory of Metrology of the ionizing radiations of the Institute of Radioprotection and Dosimetry, Rio de Janeiro-Brazil (1999). The third was organized by the IAEA and the irradiations were made in the Physikalisch-Technische Bundesanstalt PTB, Braunschweig - Federal Republic of Germany (1999-2000) [es

  13. Fast neutron spectrometry and dosimetry

    International Nuclear Information System (INIS)

    Blaize, S.; Ailloud, J.; Mariani, J.; Millot, J.P.

    1958-01-01

    We have studied fast neutron spectrometry and dosimetry through the recoil protons they produce in hydrogenated samples. In spectrometric, we used nuclear emulsions, in dosimetric, we used polyethylene coated with zinc sulphide and placed before a photomultiplier. (author) [fr

  14. Internal dosimetry technical basis manual

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-20

    The internal dosimetry program at the Savannah River Site (SRS) consists of radiation protection programs and activities used to detect and evaluate intakes of radioactive material by radiation workers. Examples of such programs are: air monitoring; surface contamination monitoring; personal contamination surveys; radiobioassay; and dose assessment. The objectives of the internal dosimetry program are to demonstrate that the workplace is under control and that workers are not being exposed to radioactive material, and to detect and assess inadvertent intakes in the workplace. The Savannah River Site Internal Dosimetry Technical Basis Manual (TBM) is intended to provide a technical and philosophical discussion of the radiobioassay and dose assessment aspects of the internal dosimetry program. Detailed information on air, surface, and personal contamination surveillance programs is not given in this manual except for how these programs interface with routine and special bioassay programs.

  15. Internal dosimetry technical basis manual

    International Nuclear Information System (INIS)

    1990-01-01

    The internal dosimetry program at the Savannah River Site (SRS) consists of radiation protection programs and activities used to detect and evaluate intakes of radioactive material by radiation workers. Examples of such programs are: air monitoring; surface contamination monitoring; personal contamination surveys; radiobioassay; and dose assessment. The objectives of the internal dosimetry program are to demonstrate that the workplace is under control and that workers are not being exposed to radioactive material, and to detect and assess inadvertent intakes in the workplace. The Savannah River Site Internal Dosimetry Technical Basis Manual (TBM) is intended to provide a technical and philosophical discussion of the radiobioassay and dose assessment aspects of the internal dosimetry program. Detailed information on air, surface, and personal contamination surveillance programs is not given in this manual except for how these programs interface with routine and special bioassay programs

  16. Dosimetry systems for radiation processing

    International Nuclear Information System (INIS)

    McLaughlin, W.L.; Desrosiers, M.F.

    1995-01-01

    Dosimetry serves important functions in radiation processing, where large absorbed doses and dose rates from photon and electron sources have to be measured with reasonable accuracy. Proven dosimetry systems are widely used to perform radiation measurements in development of new processes, validation, qualification and verification (quality control) of established processes and archival documentation of day-to-day and plant-to-plant processing uniformity. Proper calibration and traceability of routine dosimetry systems to standards are crucial to the success of many large-volume radiation processes. Recent innovations and advances in performance of systems that enhance radiation measurement assurance and process diagnostics include dose-mapping media (new radiochromic film and solutions), optical waveguide systems for food irradiation, solid-state devices for real-time and passive dosimetry over wide dose-rate and dose ranges, and improved analytical instruments and data acquisition. (author)

  17. Dosimetry for radiation processing

    International Nuclear Information System (INIS)

    Kumar, A.; Reddy, A.R.

    1994-01-01

    The last few years have seen a significant increase in the use of ionising radiation in industrial processes and also international trade in irradiated products. With this, the demand for internationally accepted dosimetric techniques, accredited to international standards has also increased which is further stimulated by the emergence of ISO-9000 series of standards in industries. The present paper describes some of the important dosimetric techniques used in radiation processing, the role of IAEA in evolving internationally accepted standards and work carried out at the Defence Laboratories, Jodhpur in the development of a cheap, broad dose range and simple dosimeter for routine dosimetry. For this polyhydroxy alcohols viz., mannitol, sorbitol and inositol were studied using the spectrophotometric read out method. Out of the alcohols studied mannitol was found to be most promising covering a dose range of 0.01 kGy - 100 kGy. (author). 26 refs., 3 figs., 1 tab

  18. Dosimetry of fast neutrons

    International Nuclear Information System (INIS)

    Jahr, R.

    1975-03-01

    Following an explanation of the physical fundamentals of neutron dosimetry, the special needs in medicine and biology are gone into. It is shown that the dose equivalent used in radiation protection simplifies in an undue manner the complicated dependence of the biological effects. The reason for this is the fact that the RBE for heavy recoil nuclei, amongst others, depends on the energy and sort of particle, whereas it is approximately equal to one for electrons independent of the energy. It is thus necessary in the fields of biology and medicine to have additional information on energy spectra of the neutrons as well as of all charged secondary particles as a function of the position in the phantom. These are obtained partly by calculation and partly by special dosemeters. The accuracy achieved so far is 5%. (ORU/LH) [de

  19. Dosimetry of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ramirez C, G; Restrepo, J; Aguirre, C A [Hospital Universitario del Valle, Cali (Colombia)

    1996-08-01

    The systemic therapy of breast cancer has also changed profoundly during the last 60 years, and in this time the integration of treatment modalities involve a major area of investigation. The dosimetry of breast cancer presents different complications which can range from the Physician`s handling of the neoplasia up to the simple aspects of physical simulation, contour design, radiation fields, irregular surfaces and computer programs containing mathematical equations which differ little or largely with the reality of the radiation distribution into the volume to be irradiated. We have studied the problem using two types of measurements to determine how the radiation distribution is in irregular surfaces, and designing an easier skill to be used with each patient, in order to optimize the treatment with respect to the simulation and verification process. (author). 7 refs.

  20. Radioiodotherapy: dosimetry planning

    International Nuclear Information System (INIS)

    Apyan, A.; Mileshin, O.; Klyopov, A.; Shishkanov, N.; Matusevich, E.; Roziev, A.

    2001-01-01

    The results of treatment of 142 case histories of 125 patients who had been treated with radioactive iodine at the Medical Radiological Research Center of Russian Academy of Medicine Sciences from 1983 to 1999 are given in the presentation. Among the patients, 35 cases of diffuse toxic goiter with signs of thyrotoxicosis of a mild degree, 25 cases of Diffuse toxic goiter with severe thyrotoxicosis, 6 cases of differentiated thyroid cancer with metastases to lymph-nodes of the neck, 30 cases of thyroid cancer with metastases to lymph-nodes of the neck and lung and 1 case of thyroid cancer with metastases to bones were diagnosed. This paper gives recommendations for individual dosimetry planning for radioiodine-therapy. (authors)

  1. Advances in electron dosimetry

    International Nuclear Information System (INIS)

    Harder, D.

    1980-04-01

    Starting from the two most important interactions of electrons with matter, energy loss and scattering, a review is given of a number of effects which are important in electron dosimetry. For determining the absorbed dose in a phantom by means of ionization chambers, imformation is required on the electron spectrum at the location of the measurement, on the stopping powers of different materials and on disturbances such as the displacement of the effective point of measurements from the centre of the chamber. By means of figures and photographs of electron traces in bubble chambers, the origin of the formation of the absorbed dose maximum in a phantom is explained. It is shown, how by multiple scattering, the similarity of dose distributions in different media can be explained and how by Monte-Carlo calculations absorbed dose distributions in the surroundings of inhomogeneities (e.g. cavities) in a phantom can be determined. (orig.) [de

  2. The Vinca dosimetry experiment

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1962-03-15

    On 15 October 1958 there occurred a very brief uncontrolled run of the zero-power reactor at the Boris Kidric Institute of Nuclear Science, Vinca, near Belgrade, Yugoslavia. During this run six persons received various doses of radiation. They were subsequently given medical treatment of a novel kind at the Curie Hospital, Paris. In atomic energy operations to date, very few accidents involving excessive radiation exposure to human beings have occurred. In fact, the cases of acute radiation injury are limited to about 30 known high exposures, few of which were in the lethal or near-lethal range. Since direct experiment to determine the effects of ionizing radiation on man is unacceptable, information on these effects has to be based on a consideration of data relating to accidental exposures, viewed in the light of the much more extensive data obtained from experiments on animals. Therefore, any direct information on the effects of radiation on humans is very valuable. The international dosimetry project described in this report was carried out at Vinca, Yugoslavia, under the auspices of the International Atomic Energy Agency to determine the precise amount of radiation to which the persons had been exposed during the accident. These dosimetry data, together with the record of the carefully observed clinical effects, are of importance both for the scientific study of radiation effects on man and for the development of methods of therapy. The experiment and measurements were carried out at the end of April 1960. The project formed part of the Agency's research programme in the field of health and safety. The results of the experiment are made available through this report to all Member States.

  3. The Vinca dosimetry experiment

    International Nuclear Information System (INIS)

    1962-03-01

    On 15 October 1958 there occurred a very brief uncontrolled run of the zero-power reactor at the Boris Kidric Institute of Nuclear Science, Vinca, near Belgrade, Yugoslavia. During this run six persons received various doses of radiation. They were subsequently given medical treatment of a novel kind at the Curie Hospital, Paris. In atomic energy operations to date, very few accidents involving excessive radiation exposure to human beings have occurred. In fact, the cases of acute radiation injury are limited to about 30 known high exposures, few of which were in the lethal or near-lethal range. Since direct experiment to determine the effects of ionizing radiation on man is unacceptable, information on these effects has to be based on a consideration of data relating to accidental exposures, viewed in the light of the much more extensive data obtained from experiments on animals. Therefore, any direct information on the effects of radiation on humans is very valuable. The international dosimetry project described in this report was carried out at Vinca, Yugoslavia, under the auspices of the International Atomic Energy Agency to determine the precise amount of radiation to which the persons had been exposed during the accident. These dosimetry data, together with the record of the carefully observed clinical effects, are of importance both for the scientific study of radiation effects on man and for the development of methods of therapy. The experiment and measurements were carried out at the end of April 1960. The project formed part of the Agency's research programme in the field of health and safety. The results of the experiment are made available through this report to all Member States

  4. Dosimetry in radionuclide therapy

    International Nuclear Information System (INIS)

    Riccabona, G.

    2001-01-01

    While it is known that therapeutic effects of radionuclides are due to absorbed radiation dose and to radiosensitivity, individual dosimetry in 'Gy' is practiced rarely in clinical Nuclear Medicine but 'doses' are described in 'mCi' or 'MBq', which is only indirectly related to 'Gy' in the target. To estimate 'Gy', the volume of the target, maximum concentration of the radiopharmaceutical in it and residence time should be assessed individually. These parameters can be obtained usually only with difficulty, involving possibly also quantitative SPET or PET, modern imaging techniques (sonography, CT, MRT), substitution of y- or positron emitting radiotracers for β - emitting radiopharmaceuticals as well as whole-body distribution studies. Residence time can be estimated by obtaining data on biological half-life of a comparable tracer and transfer of these data in the physical characteristics of the therapeutic agent. With all these possibilities for gross dosimetry the establishment of a dose-response-relation should be possible. As distribution of the radiopharmaceutical in lesions is frequently inhomogenous and microdosimetric conditions are difficult to assess in vivo as yet, it could be observed since decades that empirically set, sometimes 'fixed' doses (mCi or MBq) can also be successful in many diseases. Detailed dosimetric studies, however, are work- and cost-intensive. Nevertheless, one should be aware at a time when more sophisticated therapeutic possibilities in Nuclear Medicine arise, that we should try to estimate radiation dose (Gy) in our new methods even as differences in individual radiosensitivity cannot be assessed yet and studies to define individual radiosensitivity in lesions should be encouraged. (author)

  5. Dosimetry in intravascular brachytherapy

    International Nuclear Information System (INIS)

    Campos, Laelia Pumilla Botelho

    2000-03-01

    Among the cardiovascular diseases responsible for deaths in the adult population in almost all countries of the world, the most common is acute myocardial infarction, which generally occurs because of the occlusion of one or more coronary arteries. Several diagnostic techniques and therapies are being tested for the treatment of coronary artery disease. Balloon angioplasty has been a popular treatment which is less invasive than traditional surgeries involving revascularization of the myocardium, thus promising a better quality of life for patients. Unfortunately, the rate of restenosis (re-closing of the vessel) after balloon angioplasty is high (approximately 30-50% within the first year after treatment).Recently, the idea of delivering high radiation doses to coronary arteries to avoid or delay restenosis has been suggested. Known as intravascular brachytherapy, the technique has been used with several radiation sources, and researchers have obtained success in decreasing the rate of restenosis in some patient populations. In order to study the radiation dosimetry in the patient and radiological protection for the attending staff for this therapy, radiation dose distributions for monoenergetic electrons and photons (at nine discrete energies) were calculated for blood vessels of diameter 0.15, o,30 and 0.45 cm with balloon and wire sources using the radiation transport code MCNP4B. Specific calculations were carried out for several candidate radionuclides as well. Two s tent sources (metallic prosthesis that put inside of patient's artery through angioplasty) employing 32 P are also simulated. Advantages and disadvantages of the various radionuclides and source geometries are discussed. The dosimetry developed here will aid in the realization of the benefits obtained in patients for this promising new technology. (author)

  6. High energy dosimetry

    International Nuclear Information System (INIS)

    Ruhm, W.

    2010-01-01

    Full text: Currently, quantification of doses from high-energy radiation fields is a topical issue. This is so because high-energy neutrons play an important role for radiation exposure of air crew members and personnel outside the shielding of ion therapy facilities. In an effort to study air crew exposure from cosmic radiation in detail, two Bonner Sphere Spectrometers (BSSs) have recently been installed to measure secondary neutrons from cosmic radiation, one at the environmental research station 'Schneefernerhaus' at an altitude of 2650 m on the Zugspitze mountain, Germany, the other at the Koldewey station close to the North Pole on Spitsbergen. Based on the measured neutron fluence distributions and on fluence-to-dose conversion coefficients, mean ambient dose equivalent rate values of 75.0 ± 2.9 nSv/h and 8.7 ± 0.6 nSv/h were obtained for October 2008, respectively. Neutrons with energies above about 20 MeV contribute about 50% to dose, at 2650 m. Ambient dose equivalent rates measured by means of a standard rem counter and an extended rem counter at the Schneefernerhaus confirm this result. In order to study the response of state-of-the-art radiation instrumentation in such a high-energy radiation field, a benchmark exercise that included both measurements in and simulation of the stray neutron radiation field at the high-energy particle accelerator at GSI, Germany, were performed. This CONRAD (COordinated Network for RAdiation Dosimetry) project was funded by the European Commission, and the organizational framework was provided by the European Radiation Dosimetry Group, EURADOS. The Monte Carlo simulations of the radiation field and the experimental determination of the neutron spectra with various Bonner Sphere Spectrometers suggest the neutron fluence distributions to be very similar to those of secondary neutrons from cosmic radiation. The results of this intercomparison exercise in terms of ambient dose equivalent are also discussed

  7. Fifth international radiopharmaceutical dosimetry symposium

    International Nuclear Information System (INIS)

    Watson, E.E.; Schlafke-Stelson, A.T.

    1992-05-01

    This meeting was held to exchange information on how to get better estimates of the radiation absorbed dose. There seems to be a high interest of late in patient dosimetry; discussions were held in the light of revised risk estimates for radiation. Topics included: Strategies of Dose Assessment; Dose Estimation for Radioimmunotherapy; Dose Calculation Techniques and Models; Dose Estimation for Positron Emission Tomography (PET); Kinetics for Dose Estimation; and Small Scale Dosimetry and Microdosimetry. (VC)

  8. Dosimetry of high energy radiation

    CERN Document Server

    Sahare, P D

    2018-01-01

    High energy radiation is hazardous to living beings and a threat to mankind. The correct estimation of the high energy radiation is a must and a single technique may not be very successful. The process of estimating the dose (the absorbed energy that could cause damages) is called dosimetry. This book covers the basic technical knowledge in the field of radiation dosimetry. It also makes readers aware of the dangers and hazards of high energy radiation.

  9. Hanford internal dosimetry program manual

    International Nuclear Information System (INIS)

    Carbaugh, E.H.; Sula, M.J.; Bihl, D.E.; Aldridge, T.L.

    1989-10-01

    This document describes the Hanford Internal Dosimetry program. Program Services include administrating the bioassay monitoring program, evaluating and documenting assessments of internal exposure and dose, ensuring that analytical laboratories conform to requirements, selecting and applying appropriate models and procedures for evaluating internal radionuclide deposition and the resulting dose, and technically guiding and supporting Hanford contractors in matters regarding internal dosimetry. 13 refs., 16 figs., 42 tabs

  10. Clinical Population Pharmacokinetics and Toxicodynamics of Linezolid

    Science.gov (United States)

    Boak, Lauren M.; Rayner, Craig R.; Grayson, M. Lindsay; Paterson, David L.; Spelman, Denis; Khumra, Sharmila; Capitano, Blair; Forrest, Alan; Li, Jian

    2014-01-01

    Thrombocytopenia is a common side effect of linezolid, an oxazolidinone antibiotic often used to treat multidrug-resistant Gram-positive bacterial infections. Various risk factors have been suggested, including linezolid dose and duration of therapy, baseline platelet counts, and renal dysfunction; still, the mechanisms behind this potentially treatment-limiting toxicity are largely unknown. A clinical study was conducted to investigate the relationship between linezolid pharmacokinetics and toxicodynamics and inform strategies to prevent and manage linezolid-associated toxicity. Forty-one patients received 42 separate treatment courses of linezolid (600 mg every 12 h). A new mechanism-based, population pharmacokinetic/toxicodynamic model was developed to describe the time course of plasma linezolid concentrations and platelets. A linezolid concentration of 8.06 mg/liter (101% between-patient variability) inhibited the synthesis of platelet precursor cells by 50%. Simulations predicted treatment durations of 5 and 7 days to carry a substantially lower risk than 10- to 28-day therapy for platelet nadirs of linezolid therapy and large between-patient variability, close monitoring of patients for development of toxicity is important. Dose individualization based on plasma linezolid concentration profiles and platelet counts should be considered to minimize linezolid-associated thrombocytopenia. Overall, oxazolidinone therapy over 5 to 7 days even at relatively high doses was predicted to be as safe as 10-day therapy of 600 mg linezolid every 12 h. PMID:24514086

  11. Pharmacokinetics of BMEDA after Intravenous Administration in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Chih-Hsien Chang

    2014-01-01

    Full Text Available The pharmacokinetics of N,N-bis(2-mercapatoethly-N',N'-diethylenediamine (BMEDA, a molecule that can form a chelate with rhenium-188 (188Re to produce the 188Re-BMEDA-liposomes, was studied. In this work, beagles received a single injection of BMEDA, at doses of 1, 2, or 5 mg/kg; the concentration of BMEDA in the beagles’ plasma was then analyzed and determined by liquid chromatography-mass spectrometry/mass spectrometry. Based on the pharmacokinetic parameters of BMEDA, we found that male and female animals shared similar patterns indicating that the pharmacokinetics of BMEDA is independent of gender differences. In addition, the pharmacokinetics of BMEDA was seen to be non-linear because the increase of mean AUC0–t and AUC0–∞ values tend to be greater than dose proportional while the mean Vss and CL values of BMEDA appeared to be dose dependent. The information on the pharmacokinetics of BMEDA generated from this study will serve as a basis to design appropriate pharmacology and toxicology studies for future human use.

  12. Internal dosimetry, past and future

    International Nuclear Information System (INIS)

    Johnson, J.R.

    1989-03-01

    This paper is a review of the progress in the dosimetry of internally deposited radionuclides (internal dosimetry) since World War II. Previous to that, only naturally occurring radionuclides were available and only a limited number of studies of biokinetics and dosimetry were done. The main radionuclides studied were 226 Ra, 228 Ra, and 224 Ra but natural uranium was also studied mainly because of its toxic effect as a heavy metal, and not because it was radioactive. The effects of 226 Ra in bone, mainly from the radium dial painters, also formed the only bases for the radiotoxicity of radionuclides in bone for many years, and it is still, along with 224 Ra, the main source of information on the effects of alpha emitters in bone. The publications of the International Commission on Radiological Protection that have an impact on internal dosimetry are used as mileposts for this review. These series of publications, more than any other, represent a broad consensus of opinion within the radiation protection community at the time of their publication, and have formed the bases for radiation protection practice throughout the world. This review is not meant to be exhaustive; it is meant to be a personnel view of the evolution of internal dosimetry, and to present the author's opinion of what the future directions in internal dosimetry will be. 39 refs., 2 tabs

  13. Cefazolin pharmacokinetics in cats under surgical conditions.

    Science.gov (United States)

    Albarellos, Gabriela A; Montoya, Laura; Passini, Sabrina M; Lupi, Martín P; Lorenzini, Paula M; Landoni, María F

    2017-10-01

    Objectives The aim of this study was to determine the plasma pharmacokinetic profile, tissue concentrations and urine elimination of cefazolin in cats under surgical conditions after a single intravenous dose of 20 mg/kg. Methods Intravenous cefazolin (20 mg/kg) was administered to nine young mixed-breed cats 30 mins before they underwent surgical procedures (ovariectomy or orchiectomy). After antibiotic administration, samples from blood, some tissues and urine were taken. Cefazolin concentrations were determined in all biological matrices and pharmacokinetic parameters were estimated. Results Initial plasma concentrations were high (C p(0) , 134.80 ± 40.54 µg/ml), with fast and moderately wide distribution (distribution half-life [t ½(d) ] 0.16 ± 0.15 h; volume of distribution at steady state [V (d[ss]) ] 0.29 ± 0.10 l/kg) and rapid elimination (body clearance [Cl B ], 0.21 ± 0.06 l/h/kg; elimination half-life [t ½ ], 1.18 ± 0.27 h; mean residence time 1.42 ± 0.36 h). Thirty to 60 mins after intravenous administration, cefazolin tissue concentrations ranged from 9.24 µg/ml (subcutaneous tissue) to 26.44 µg/ml (ovary). The tissue/plasma concentration ratio ranged from 0.18 (muscle) to 0.58 (ovary). Cefazolin urine concentrations were high with 84.2% of the administered dose being eliminated in the first 6 h postadministration. Conclusions and relevance Cefazolin plasma concentrations remained above a minimum inhibitory concentration of ⩽2 µg/ml up to 4 h in all the studied cats. This suggests that a single intravenous dose of 20 mg/kg cefazolin would be adequate for perioperative prophylactic use in cats.

  14. Clinical Pharmacokinetics of Paclitaxel Monotherapy

    DEFF Research Database (Denmark)

    Stage, Tore B; Bergmann, Troels K; Kroetz, Deanna L

    2018-01-01

    Paclitaxel is an anticancer agent efficacious in the treatment of ovarian, breast, and lung cancer. Due to a strong link between the pharmacokinetics and therapeutic efficacy of paclitaxel, we reviewed the literature on paclitaxel pharmacokinetics. Systematic data mining was performed to extract ...

  15. 11. International conference on solid radiation dosimetry

    International Nuclear Information System (INIS)

    Krylova, I.V.

    1996-01-01

    The main problems discussed during the international conference on solid radiation dosimetry which took place in June 1995 in Budapest are briefly considered. These are the basic physical processes, materials applied for dosimetry, special techniques, personnel monitoring, monitoring of environmental effects, large-dose dosimetry, clinic dosimetry, track detector used for dosimetry, dosimetry in archaeology and geology, equipment and technique for dosimetric measurements. The special attention was paid to superlinearity in the TLD-100 (LiF, Mg, Ti) response function when determining doses of gamma radiation, heavy charged particles, low-energy particle fluxes in particular. New theoretical models were considered

  16. Pharmacokinetics of Snake Venom

    Directory of Open Access Journals (Sweden)

    Suchaya Sanhajariya

    2018-02-01

    Full Text Available Understanding snake venom pharmacokinetics is essential for developing risk assessment strategies and determining the optimal dose and timing of antivenom required to bind all venom in snakebite patients. This review aims to explore the current knowledge of snake venom pharmacokinetics in animals and humans. Literature searches were conducted using EMBASE (1974–present and Medline (1946–present. For animals, 12 out of 520 initially identified studies met the inclusion criteria. In general, the disposition of snake venom was described by a two-compartment model consisting of a rapid distribution phase and a slow elimination phase, with half-lives of 5 to 48 min and 0.8 to 28 h, respectively, following rapid intravenous injection of the venoms or toxins. When the venoms or toxins were administered intramuscularly or subcutaneously, an initial absorption phase and slow elimination phase were observed. The bioavailability of venoms or toxins ranged from 4 to 81.5% following intramuscular administration and 60% following subcutaneous administration. The volume of distribution and the clearance varied between snake species. For humans, 24 out of 666 initially identified publications contained sufficient information and timed venom concentrations in the absence of antivenom therapy for data extraction. The data were extracted and modelled in NONMEM. A one-compartment model provided the best fit, with an elimination half-life of 9.71 ± 1.29 h. It is intended that the quantitative information provided in this review will provide a useful basis for future studies that address the pharmacokinetics of snakebite in humans.

  17. PK/DB: database for pharmacokinetic properties and predictive in silico ADME models.

    Science.gov (United States)

    Moda, Tiago L; Torres, Leonardo G; Carrara, Alexandre E; Andricopulo, Adriano D

    2008-10-01

    The study of pharmacokinetic properties (PK) is of great importance in drug discovery and development. In the present work, PK/DB (a new freely available database for PK) was designed with the aim of creating robust databases for pharmacokinetic studies and in silico absorption, distribution, metabolism and excretion (ADME) prediction. Comprehensive, web-based and easy to access, PK/DB manages 1203 compounds which represent 2973 pharmacokinetic measurements, including five models for in silico ADME prediction (human intestinal absorption, human oral bioavailability, plasma protein binding, blood-brain barrier and water solubility). http://www.pkdb.ifsc.usp.br

  18. Radiotherapy gel dosimetry

    International Nuclear Information System (INIS)

    Baldock, C.

    2002-01-01

    shapes and sizes while sparing normal tissue. The situation is further complicated if the normal tissues are critical organs or are particularly sensitive to radiation. Radiotherapy techniques employed to obtain a closer conformation of the dose distribution to the tumour volume are referred to as conformal radiotherapy techniques. The clinical implementation of conformal therapy has been delayed by limitations in the verification of conformal dose distributions calculated by treatment planning systems prior to the irradiation of the patient and the verification of complex treatments during its delivery to the patient. There are several aspects of conformal therapy that complicate dose verification. To achieve the dose distributions conforming to complex 3D volumes, high dose gradients arise in the treatment volume. Further, overdose or underdose regions can exist when separate radiation fields are used to deliver additional radiation. These aspects require that practical dose measurement (dosimetry) techniques be able to integrate dose over time and easily measure dose distributions in 3D with high spatial resolution. Traditional dosimeters, such as ion chambers, thermoluminescent dosimeters and radiographic film do not fulfil these requirements. Novel gel dosimetry techniques are being developed in which dose distributions can potentially be determined in vitro in 3D using anthropomorphic phantoms to simulate a clinically irradiated situation. As long ago as the 1950's, radiation-induced colour change in dyes was used to investigate radiation doses in gels. It was subsequently shown that radiation induced changes in nuclear magnetic resonance (NMR) relaxation properties of gels infused with conventional Fricke dosimetry solutions could be measured using magnetic resonance imaging (MRI). In Fricke gels, Fe 2+ ions in ferrous sulphate solutions are usually dispersed throughout a gelatin, agarose or PVA matrix. Radiation-induced changes in the dosimeters are considered to

  19. Systemic and ocular pharmacokinetics of N-4-benzoylaminophenylsulfonylglycine (BAPSG), a novel aldose reductase inhibitor

    OpenAIRE

    Sunkara, Gangadhar; Ayalasomayajula, Surya P.; Rao, Cheruku S.; Vennerstrom, Jonathan L.; DeRuiter, Jack; Kompella, Uday B.

    2004-01-01

    To better develop N-[4-(benzoylamino)phenylsulfonyl]glycine (BAPSG), a potent and selective aldose reductase inhibitor capable of delaying the progression of ocular diabetic complications, the objective of this study was to assess its pharmacokinetics. The plasma pharmacokinetics of BASPG was assessed in male Sprague-Dawley rats following intravenous, intraperitoneal and oral routes of administration and its distribution to various tissues including those of the eye was studied following intr...

  20. Characterising an aluminium oxide dosimetry system.

    Science.gov (United States)

    Conheady, Clement F; Gagliardi, Frank M; Ackerly, Trevor

    2015-09-01

    In vivo dosimetry is recommended as a defence-in-depth strategy in radiotherapy treatments and is currently employed by clinics around the world. The characteristics of a new optically stimulated luminescence dosimetry system were investigated for the purpose of replacing an aging thermoluminescence dosimetry system for in vivo dosimetry. The stability of the system was not sufficient to satisfy commissioning requirements and therefore it has not been released into clinical service at this time.

  1. Dosimetry in nuclear power plants

    International Nuclear Information System (INIS)

    Lastra B, J. A.

    2008-12-01

    To control the occupationally exposed personnel dose working at the Laguna Verde nuclear power plant, two types of dosemeters are used, the thermoluminescent (TLD) which is processed monthly, and the direct reading dosemeter that is electronic and works as daily control of personal dose. In the case of the electronic dosemeters of direct reading conventional, the readings and dose automatic registers and the user identity to which he was assigned to each dosemeter was to carry out the restricted area exit. In activities where the ionizing radiation sources are not fully characterized, it is necessary to relocate the personal dosemeter or assigned auxiliary dosemeters (TLDs and electronics) to determine the dose received by the user to both whole body and in any specific area of it. In jobs more complicated are used a tele dosimetry system where the radiation protection technician can be monitoring the user dose to remote control, the data transmission is by radio. The dosimetry activities are documented in procedures that include dosemeter inventories realization, the equipment and dosemeters calibration, the dosimetry quality control and the discrepancies investigation between the direct reading and TLD systems. TLD dosimetry to have technical expertise in direct and indirect dosimetry and two technicians in TLD dosimetry; electronic dosimetry to have 4 calibration technicians. For the electronic dosemeters are based on a calibrator source of Cesium-137. TLD dosemeters to have an automatic radiator, an automatic reader which can read up to 100 TLD dosemeters per hour and a semiautomatic reader. To keep the equipment under a quality process was development a process of initial entry into service and carried out a periodic verification of the heating cycles. It also has a maintenance contract for the equipment directly with the manufacturer to ensure their proper functioning. The vision in perspective of the dosimetry services of Laguna Verde nuclear power plant

  2. Neutron personnel dosimetry

    International Nuclear Information System (INIS)

    Griffith, R.V.

    1982-01-01

    The measurement of neutron exposures to personnel is an issue that has received increased attention in the last few years. It is important to consider key aspects of the whole dosimetry system when developing dose estimates. This begins with selection of proper dosimeters and survey instruments, and extends through the calibration methods. One must match the spectral response and sensitivity of the dosimeter to the spectral characteristics of the neutron fields. Threshold detectors that are insensitive to large fractions of neutrons in the lower energy portion of reactor spectra should be avoided. Use of two or more detectors with responses that complement each other will improve measurement quality. It is important to understand the spectral response of survey instruments, so that spectra which result in significant overresponse do not lead to overestimation of dose. Calibration sources that do not match operational field spectra can contribute to highly erroneous results. In those situations, in-field calibration techniques should be employed. Although some detection developments have been made in recent years, a lot can be done with existing technology until fully satisfactory, long term solutions are obtained

  3. Fast neutron dosimetry

    International Nuclear Information System (INIS)

    DeLuca, P.M. Jr.; Pearson, D.W.

    1991-01-01

    During 1988--1990 the magnetic resonance dosimetry project was completed, as were the 250 MeV proton shielding measurements. The first cellular experiment using human cells in vitro at the 1 GeV electron storage ring was also accomplished. More detail may be found in DOE Report number-sign DOE/EV/60417-002 and the open literature cited in the individual progress subsections. We report Kinetic Energy Released in Matter (KERMA), factor measurements in several elements of critical importance to neutron radiation therapy and radiation protection for space habitation and exploration for neutron energies below 30 MeV. The results of this effort provide the only direct measurements of the oxygen and magnesium kerma factors above 20 MeV neutron energy, and the only measurements of the iron kerma factor above 15 MeV. They provide data of immediate relevance to neutron radiotherapy and impose strict criteria for normalizing and testing nuclear models used to calculate kerma factors at higher neutron energies

  4. Dosimetry in radioisotope placentography

    International Nuclear Information System (INIS)

    Sastry, K.G.K.; Reddy, A.R.; Nagaratnam, A.

    1976-01-01

    Radionuclide investigation of the placenta is being widely used in recent years for the diagnosis and management of vaginal bleeding in the third trimester of pregnancy. One is, therefore, concerned about the radiation exposure to the foetus during such procedures. In the present communication a precise method of estimation of radiation doses is presented. A concept termed 'effective absorbed dose constant' is utilized to enable the absorbed fractions and equilibrium absorbed dose constants to be more easily employed in radiation dose estimations. Tables of the effective absorbed dose constants for radionuclides like 131 I, 123 I, sup(113m)Tc, sup(99m)Tc, 67 Ga, and 51 Cr, are given for different masses and shapes. Masses of different organs of both mother and foetus at different periods of pregnancy and the biological turnover data for different radiopharmaceuticals are reviewed and typical values are presented. Radiation doses to different organs of both mother and foetus at the 30th week of pregnancy are finally estimated for 131 I-HSA, 123 I-SHA, sup(99m)Tc-HSA and sup(113m)In-chloride. The advantage of the effective absorbed dose constants in radiation dosimetry in general is discussed. The relative merits of different radiopharmaceuticals for placental investigations are brought out in comparison with antenatal pelvimetric and abdominal X-ray investigations, from the point of view of radiation doses. (author)

  5. Pharmacokinetics of fexofenadine

    DEFF Research Database (Denmark)

    Lappin, Graham; Shishikura, Yoko; Jochemsen, Roeline

    2010-01-01

    with an oral unlabelled therapeutic dose (120mg). Plasma was collected from all 3 periods and analysed for both total (14)C content and parent drug by accelerator mass spectrometry (AMS). For period 3, plasma samples were also analysed using HPLC-fluorescence to determine total drug concentration. Urine...

  6. Miniature semiconductor detectors for in vivo dosimetry

    International Nuclear Information System (INIS)

    Rosenfeld, A. B.; Cutajar, D.; Lerch, M. L. F.; Takacs, G.; Cornelius, I. M.; Yudelev, M.; Zaider, M.

    2006-01-01

    Silicon mini-semiconductor detectors are found in wide applications for in vivo personal dosimetry and dosimetry and Micro-dosimetry of different radiation oncology modalities. These applications are based on integral and spectroscopy modes of metal oxide semiconductor field effect transistor and silicon p-n junction detectors. The advantages and limitations of each are discussed. (authors)

  7. Fundamentals of x-ray dosimetry

    International Nuclear Information System (INIS)

    Roesch, W.C.

    1976-01-01

    Fundamental information about x-ray dosimetry is presented. Definitions are given and expanded on for dose, absorbed dose including microdosimetry, radiation physics (properties of the radiation that are important to dosimetry), and dosimetry (how the properties are dealt with in determining dose). 5 figs, 12 refs

  8. Dose- and time-dependent pharmacokinetics of apigenin trimethyl ether.

    Science.gov (United States)

    Elhennawy, Mai Gamal; Lin, Hai-Shu

    2018-06-15

    Apigenin trimethyl ether (5,7,4'-trimethoxyflavone, ATE), one of the key polymethoxyflavones present in black ginger (rhizome of Kaempferia parviflora) possesses various health-promoting activities. To optimize its medicinal application, the pharmacokinetics of ATE was assessed in Sprague-Dawley rats with emphases to identify the impacts from dose and repeated dosing on its major pharmacokinetic parameters. Plasma ATE levels were monitored by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Upon single intravenous administration (2 mg/kg), plasma levels of ATE declined through an apparent first-order process while dose-escalation to 4 and 8 mg/kg led to its non-linear disposition, which could be described by the Michaelis-Menten model. Similarly, dose-dependent oral pharmacokinetics was confirmed and when the dose was escalated from 5 to 15 and 45 mg/kg, much longer mean residence time (MRT 0→last ), higher dose-normalized maximal plasma concentration (C max /Dose) and exposure (AUC/Dose) were observed at 15 and/or 45 mg/kg. One-week daily oral administration of ATE at 15 mg/kg caused its accelerated elimination and the plasma exposure (AUC) after intravenous (2 mg/kg) and oral administration (15 mg/kg) dropped ~40 and 60%, respectively. As ATE displayed both dose- and time-dependent pharmacokinetics, caution is needed in the medicinal applications of ATE and/or black ginger. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. [Pharmacokinetic of four alkaloids of Yanshu injection in Beagel dogs].

    Science.gov (United States)

    Liu, Jiping; Xue, Mei; Huang, Xin; Wang, Shu; Jiang, Zhenzhou; Zhang, Luyong

    2012-06-01

    For studying the pharmacokinetic of Yanshu injections in Beagel dogs, a sensitive and reproducible LC-MS method for quantitative determination of matrine, oxymatrine, sophocarpine and oxysophocarpine in dog's plasma were developed and validated using monocrotaline as an internal standard after iv of Yanshu injections (Sophorae Flavescentis Radix and Heterosmilacis Japonicae Rhizoma). The separation of plasma samples was performed on a CN column by isocratic elution with methanol-10 mmol x L(-1) NH4Ac-0.02% HCOOH-H2O 90:10 as the mobile phase. The plasma concentration of four kinds of alkaloids were calculated in dog plasta by detection of healthy dogs given Yanshu injection fluid after in twelve hours of plasma samples, All data of concentration-time of four kinds of alkaloids were treated with pharmacokinetics program DAS 2. 0. MT, OMT, SP and OSP have a good linear relationship in 0.01-16.0, 0.02-60.0, 0.01-4.0, 0.02-16.0 mg x L(-1), respectively. The average recoveries were more than 90% and the RSD of precision and stability of the test were less than 6.4% iv 1.2 g x kg(-1) Yanshu injection, four kinds of alkaloids in rats meet the two-compartment open pharmacokinetic model, Cmax and the concentration of the original liquid in the proportion of the basic line, the AUC(0-infinity) of matrine and oxymatrine, sophocarpine and oxysophocarpine compared to the original both in the proportion of liquid increases, the MRT(0-infinity) and t(1/2z) of matrine and sophocarpine were less than oxymatrine and oxysophocarpine; four kinds of alkaloids apparent volume of distribution matrine > oxymatrine, sophocarpine > oxysophocarpine. A method with high recovery rate and good stabilitywas established to determine the blood concentration of MT, OMT, SP, OSP in Yanshu injection and applied in its pharmacokinetics successfully.

  10. Information from the Dosimetry Service

    CERN Multimedia

    2006-01-01

    Please note the following opening hours of the Service: In June: Every morning from 8:30 to 12:00 In July: Mondays, Wednesdays and Fridays from 8:30 to 11:30 Closed all day on Tuesdays and Thursdays From 31st July onwards: Every morning from 8:30 to 12:00 The Service is closed in the afternoons. We should like to remind you that dosimeters cannot be sent to customers by internal mail. Short-term dosimeters (VCTs) must always be returned to the Service after use and must not be left on the racks in the experimental areas or in the secretariats. Dosimetry Service Tel 72155 Bldg. 24 E 011 Dosimetry.service@cern.ch http://cern.ch/rp-dosimetry

  11. Fundamentals of Dosimetry. Chapter 3

    Energy Technology Data Exchange (ETDEWEB)

    Yoshimura, E. M. [Universidade de São Paulo, São Paulo (Brazil)

    2014-09-15

    Determination of the energy imparted to matter by radiation is the subject of dosimetry. The energy deposited as radiation interacts with atoms of the material, as seen in the previous chapter. The imparted energy is responsible for the effects that radiation causes in matter, for instance, a rise in temperature, or chemical or physical changes in the material properties. Several of the changes produced in matter by radiation are proportional to the absorbed dose, giving rise to the possibility of using the material as the sensitive part of a dosimeter. Also, the biological effects of radiation depend on the absorbed dose. A set of quantities related to the radiation field is also defined within the scope of dosimetry. It will be shown in this chapter that, under special conditions, there are simple relations between dosimetric and field description quantities. Thus, the framework of dosimetry is the set of physical and operational quantities that are studied in this chapter.

  12. External audit in radiotherapy dosimetry

    International Nuclear Information System (INIS)

    Thwaites, D.I.; Western General Hospital, Edinburgh

    1996-01-01

    Quality audit forms an essential part of any comprehensive quality assurance programme. This is true in radiotherapy generally and in specific areas such as radiotherapy dosimetry. Quality audit can independently test the effectiveness of the quality system and in so doing can identify problem areas and minimize their possible consequences. Some general points concerning quality audit applied to radiotherapy are followed by specific discussion of its practical role in radiotherapy dosimetry, following its evolution from dosimetric intercomparison exercises to routine measurement-based on-going audit in the various developing audit networks both in the UK and internationally. Specific examples of methods and results are given from some of these, including the Scottish+ audit group. Quality audit in radiotherapy dosimetry is now well proven and participation by individual centres is strongly recommended. Similar audit approaches are to be encouraged in other areas of the radiotherapy process. (author)

  13. Insulin aspart pharmacokinetics

    DEFF Research Database (Denmark)

    Rasmussen, Christian Hove; Roge, Rikke Meldgaard; Ma, Zhulin

    2014-01-01

    Background: Insulin aspart (IAsp) is used by many diabetics as a meal-time insulin to control postprandial glucose levels. As is the case with many other insulin types, the pharmacokinetics (PK), and consequently the pharmacodynamics (PD), is associated with clinical variability, both between...... to investigate and quantify the properties of the subcutaneous depot. Data from Brange et al. (1990) are used to determine the effects of insulin chemistry in subcutis on the absorption rate. Intravenous (i.v.) bolus and infusion PK data for human insulin are used to understand and quantify the systemic...... distribution and elimination (Porksen et al., 1997; Sjostrand et al., 2002). PK and PD profiles for type 1 diabetics from Chen et al. (2005) are analyzed to demonstrate the effects of IAsp antibodies in terms of bound and unbound insulin. PK profiles from Thorisdottir et al. (2009) and Ma et al. (2012b...

  14. Effect of gemfibrozil on the pharmacokinetics of mitiglinide in rats.

    Science.gov (United States)

    Jin, L; Cao, Q

    2012-01-01

    A sensitive and specific method was developed and validated for the determination of mitiglinide in plasma using LC-MS/MS. The effect of gemfibrozil on the pharmacokinetics of orally administered mitiglinide in rats was investigated. The validated method in positive electrospray ionization mode using MRM and fully validated according to commonly accepted criteria. The desired sensitivity of mitiglinide was achieved with an LOQ of 0.5 ng/mL and the short run time was suitable for analysis of the large batches of samples. The method was successfully used to analyze rats plasma samples for application in pharmacokinetic studies. Pharmacokinetic parameters of mitiglinide were determined in rats following oral (0.25, 0.5, 1 mg/kg) administration to rats in the presence and absence of gemfibrozil (1 mg/kg). Compared to those animals in an oral control group (given mitiglinide alone), the area under the plasma concentration-time curve (AUC) of mitiglinide were increased significantly by 2.8, 3.5, 4.1-fold (0.25, 0.5, 1 mg/kg) by gemfibrozil, respectively. Consequently, the bioavailability of mitiglinide in the presence of gemfibrozil was significantly enhanced compared to that in oral control group (only mitiglinide). Gemfibrozil significantly enhanced the oral bioavailability of mitiglinide, suggesting that concurrent use of gemfibrozil and mitiglinide should be monitored closely for potential drug interactions. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Dosimetry standards for radiation processing

    International Nuclear Information System (INIS)

    Farrar, H. IV

    1999-01-01

    For irradiation treatments to be reproducible in the laboratory and then in the commercial environment, and for products to have certified absorbed doses, standardized dosimetry techniques are needed. This need is being satisfied by standards being developed by experts from around the world under the auspices of Subcommittee E10.01 of the American Society for Testing and Materials (ASTM). In the time period since it was formed in 1984, the subcommittee has grown to 150 members from 43 countries, representing a broad cross-section of industry, government and university interests. With cooperation from other international organizations, it has taken the combined part-time effort of all these people more than 13 years to complete 24 dosimetry standards. Four are specifically for food irradiation or agricultural applications, but the majority apply to all forms of gamma, x-ray, Bremsstrahlung and electron beam radiation processing, including dosimetry for sterilization of health care products and the radiation processing of fruits, vegetables, meats, spices, processed foods, plastics, inks, medical wastes and paper. An additional 6 standards are under development. Most of the standards provide exact procedures for using individual dosimetry systems or for characterizing various types of irradiation facilities, but one covers the selection and calibration of dosimetry systems, and another covers the treatment of uncertainties. Together, this set of standards covers essentially all aspects of dosimetry for radiation processing. The first 20 of these standards have been adopted in their present form by the International Organization of Standardization (ISO), and will be published by ISO in 1999. (author)

  16. 'Hot particle' intercomparison dosimetry

    International Nuclear Information System (INIS)

    Kaurin, D.G.L.; Baum, J.W.; Charles, M.W.; Darley, D.P.J.; Durham, J.S.; Scannell, M.J.; Soares, C.G.

    1996-01-01

    Dosimetry measurements of four 'hot particles' were made at different density thickness values using five different methods. The hot particles had maximum dimensions of 650 μm and maximum beta energies of 0.97, 046, 0.36, and 0.32 MeV. Absorbers were used to obtain the dose at different depths for each dosimeter. Measurements were made using exoelectron dosimeters, an extrapolation chamber, NE Extremity Tape Dosimeters (tm), Eberline RO-2 and RO-2A survey meters, and two sets of GafChromic (tm) dye film with each set read out at a different institution. From these results the dose was calculated averaged over 1 cm 2 of tissue at 18, 70, 125, and 400 μm depth. Comparisons of tissue-dose averaged over 1 cm 2 for 18, 70, and 125 μm depth based on interpolated measured values, were within 30% for the GafChromic (tm) dye film, extrapolation chamber, NE Extremity Tape Dosimeters (tm), and Eberline RO-2 and 2A (tm) survey meters except for the hot particle with 0.46 MeV maximum beta energy. The results for this source showed differences of up to 60%. The extrapolation chamber and NE Extremity Tape dosimeters under-responded for measurements at 400 μm by about a factor of 2 compared with the GafChromic dye films for two hot particles with maximum beta energy of 0.32 and 0.36 MeV which each emitted two 100% 1 MeV photons per disintegration. Tissue doses determined using exoelectron dosimeters were a factor of 2 to 5 less than those determined using other dosimeters, possibly due to failures of the equipment. (author)

  17. Pharmacokinetics of clomipramine during pregnancy

    NARCIS (Netherlands)

    Ter Horst, P G J; Proost, J H; Smit, J P; Vries, M T; de Jong-van den Berg, Lolkje; Wilffert, B

    2015-01-01

    Clomipramine is one of the drugs for depression during pregnancy; however, pharmacokinetic data of clomipramine and its active metabolite desmethylclomipramine in this vulnerable period are lacking. In this study, we describe clomipramine and desmethylclomipramine concentrations including their

  18. Personal dosimetry and information platforms

    International Nuclear Information System (INIS)

    Sanchez Hidalgo, M.; Galan Montenegro, P.; Bodineau Gil, C.; Hernandez Rodriguez, R.; Jimenez Nartin, A.; Cano Sanchez, J. J.

    2011-01-01

    One question often raised by the hospital personnel dosimetry is the high incidence in the no monthly turnover of dosimeters, which is currently a high number of administrative dose assignments. The high number of workers with personal dosimetry and in many cases, the dispersion of workplaces makes it impossible to personalized management. To make a more direct and personal, and transmit information quickly and with guaranteed reception, has developed and implemented a system of personalized dosimetric information through messaging Short Message Service (SMS) and access to the history of dosimetric dosimetric and management through web space Service Hospital Radio physics.

  19. External dosimetry sources and shielding

    International Nuclear Information System (INIS)

    Calisto, Washington

    1994-01-01

    A definition of external dosimetry r external sources dosimetry,physical and mathematical treatment of the interaction of gamma radiation with a minimal area in that direction. Concept of attenuation coefficient, cumulated effect by polyenergetic sources, exposition rate, units, cumulated dose,shielding, foton shielding, depth calculation, materials used for shielding.Beta shielding, consideration of range and maximum β energy , low stopping radiation by use of low Z shielding. Tables for β energy of β emitters, I (tau) factor, energy-range curves for β emitters in aqueous media, gamma attenuation factors for U, W and Pb. Y factor for bone tissue,muscle and air, build-up factors

  20. Characterization of internal dosimetry practices

    International Nuclear Information System (INIS)

    Traub, R.J.; Heid, K.R.; Mann, J.C.

    1983-01-01

    Current practices in internal dosimetry at DOE facilities were evaluated with respect to consistency among DOE Contractors. All aspects of an internal dosimetry program were addressed. Items considered include, but are not necessarily limited to, record systems and ease of information retrieval; ease of integrating internal dose and external dose; modeling systems employed, including ability to modify models depending on excretion data, and verification of computer codes utilized; bioassay procedures, including quality control; and ability to relate air concentration data to individual workers and bioassay data. Feasibility of uranium analysis in solution by laser fluorescence excitation at uranium concentrations of one part per billion was demonstrated

  1. Information from the Dosimetry Service

    CERN Multimedia

    2006-01-01

    CERN Staff and Users can now consult their dose records for an individual or an organizational unit with HRT. Please see more information on our web page: http://cern.ch/rp-dosimetry. The Dosimetry Service is open every morning from 8.30 to 12.00 and is closed in the afternoons. We would like to remind you that dosimeters cannot be sent to customers by internal mail. Short-term dosimeters (VCT's) must always be returned to the Service after use and must not be left on the racks in the experimental areas or in the secretariats.

  2. Information from the Dosimetry Service

    CERN Multimedia

    2006-01-01

    CERN Staff and Users can now consult their dose records for an individual or an organizational unit with HRT. Please see more information on our web page http://cern.ch/rp-dosimetry. The Dosimetry Service is open every morning from 8.30 - 12.00, and closed in the afternoons. We would like to remind you that dosimeters cannot be sent to customers by internal mail. Short-term dosimeters (VCT's) must always be returned to the Service after use and must not be left on the racks in the experimental areas or in the secretariats.

  3. Calorimetric dosimetry of reactor radiation

    International Nuclear Information System (INIS)

    Radak, B.; Markovic, V.; Draganic, I.

    1961-01-01

    Calorimetric dosimetry of reactor radiation is relatively new reactor dosimetry method and the number of relevant papers is rather small. Some difficulties in applying standard methods (chemical dosemeters, ionization chambers) exist because of the complexity of radiation. In general application of calorimetric dosemeters for measuring absorbed doses is most precise. In addition to adequate choice of calorimetric bodies there is a possibility of determining the yields of each component of the radiation mixture in the total absorbed dose. This paper contains a short review of the basic calorimetry methods and some results of measurements at the RA reactor in Vinca performed by isothermal calorimeter [sr

  4. Radiation dosimetry and radiation biophysics

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    Radiation dosimetry and radiation biophysics are two closely integrated programs whose joint purpose is to explore the connections between the primary physical events produced by radiation and their biological consequences in cellular systems. The radiation dosimetry program includes the theoretical description of primary events and their connection with the observable biological effects. This program also is concerned with the design and measurement of physical parameters used in theory or to support biological experiments. The radiation biophysics program tests and uses the theoretical developments for experimental design, and provides information for further theoretical development through experiments on cellular systems

  5. Radiation dosimetry and radiation biophysics

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    Radiation dosimetry and radiation biophysics are two closely integrated programs whose joint purpose is to explore the connections between the primary physical events produced by radiation and their biological consequences in cellular systems. The radiation dosimetry program includes the theoretical description of primary events and their connection with the observable biological effects. This program also is concerned with design and measurement of those physical parameters used in the theory or to support biological experiments. The radiation biophysics program tests and makes use of the theoretical developments for experimental design. Also, this program provides information for further theoretical development through experiments on cellular systems

  6. Physiologic and Pharmacokinetic Changes in Pregnancy

    Directory of Open Access Journals (Sweden)

    Maged eCostantine

    2014-04-01

    Full Text Available Physiologic changes in pregnancy induce profound alterations to the pharmacokinetic properties of many medications. These changes affect distribution, absorption, metabolism, and excretion of drugs, and thus may impact their pharmacodynamic properties during pregnancy. Pregnant women undergo several adaptations in many organ systems. Some adaptations are secondary to hormonal changes in pregnancy, while others occur to support the gravid woman and her developing fetus. Some of the changes in maternal physiology during pregnancy include, for example, increased maternal fat and total body water, decreased plasma protein concentrations, especially albumin, increased maternal blood volume, cardiac output and blood flow to the kidneys and uteroplacental unit, and decreased blood pressure. The maternal blood volume expansion occurs at a larger proportion than the increase in red blood cell mass, which results in physiologic anemia and hemodilution. Other physiologic changes include increased tidal volume, partially compensated respiratory alkalosis, delayed gastric emptying and gastrointestinal motility, and altered activity of hepatic drug metabolizing enzymes. Understating these changes and their profound impact on the pharmacokinetic properties of drugs in pregnancy is essential to optimize maternal and fetal health.

  7. Alanine EPR dosimetry of therapeutic irradiators

    International Nuclear Information System (INIS)

    Bugay, O.; Bartchuk, V.; Kolesnik, S.; Mazin, M.; Gaponenko, H.

    1999-01-01

    The high-dose alanine EPR dosimetry is a very precise method in the dose range 1-100 kGy. The system is used generally as the standard high-dose transfer dosimetry in many laboratories. This is comparatively expensive technique so it is important to use it as a more universal dosimetry system also in the middle and low dose ranges. The problems of the middle-dose alanine dosimetry are discussed and the solution of several problems is proposed. The alanine EPR dosimetry has been applied to the dose measurements of medical irradiators in the Kiev City Oncology Center. (author)

  8. PHARMACOKINETIC RESEARCHES AND PRACTICAL MEDICINE

    Directory of Open Access Journals (Sweden)

    V. G. Belolipetskaya

    2015-12-01

    Full Text Available An article gives in a comprehensive manner the main idea of pharmacokinetics, as the science about rules of substances behavior in the internal environment of the organism, as well as of main parameters of pharmacokinetic researches. The article provides vivid and very  persuasive examples of high practical importance of this science both for creating new medical forms of drugs and for choosing the optimal of therapy regime.

  9. PHARMACOKINETIC RESEARCHES AND PRACTICAL MEDICINE

    Directory of Open Access Journals (Sweden)

    V. G. Belolipetskaya

    2005-01-01

    Full Text Available An article gives in a comprehensive manner the main idea of pharmacokinetics, as the science about rules of substances behavior in the internal environment of the organism, as well as of main parameters of pharmacokinetic researches. The article provides vivid and very  persuasive examples of high practical importance of this science both for creating new medical forms of drugs and for choosing the optimal of therapy regime.

  10. TestDose: A nuclear medicine software based on Monte Carlo modeling for generating gamma camera acquisitions and dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, Marie-Paule, E-mail: marie-paule.garcia@univ-brest.fr; Villoing, Daphnée [UMR 1037 INSERM/UPS, CRCT, 133 Route de Narbonne, 31062 Toulouse (France); McKay, Erin [St George Hospital, Gray Street, Kogarah, New South Wales 2217 (Australia); Ferrer, Ludovic [ICO René Gauducheau, Boulevard Jacques Monod, St Herblain 44805 (France); Cremonesi, Marta; Botta, Francesca; Ferrari, Mahila [European Institute of Oncology, Via Ripamonti 435, Milano 20141 (Italy); Bardiès, Manuel [UMR 1037 INSERM/UPS, CRCT, 133 Route de Narbonne, Toulouse 31062 (France)

    2015-12-15

    Purpose: The TestDose platform was developed to generate scintigraphic imaging protocols and associated dosimetry by Monte Carlo modeling. TestDose is part of a broader project (www.dositest.com) whose aim is to identify the biases induced by different clinical dosimetry protocols. Methods: The TestDose software allows handling the whole pipeline from virtual patient generation to resulting planar and SPECT images and dosimetry calculations. The originality of their approach relies on the implementation of functional segmentation for the anthropomorphic model representing a virtual patient. Two anthropomorphic models are currently available: 4D XCAT and ICRP 110. A pharmacokinetic model describes the biodistribution of a given radiopharmaceutical in each defined compartment at various time-points. The Monte Carlo simulation toolkit GATE offers the possibility to accurately simulate scintigraphic images and absorbed doses in volumes of interest. The TestDose platform relies on GATE to reproduce precisely any imaging protocol and to provide reference dosimetry. For image generation, TestDose stores user’s imaging requirements and generates automatically command files used as input for GATE. Each compartment is simulated only once and the resulting output is weighted using pharmacokinetic data. Resulting compartment projections are aggregated to obtain the final image. For dosimetry computation, emission data are stored in the platform database and relevant GATE input files are generated for the virtual patient model and associated pharmacokinetics. Results: Two samples of software runs are given to demonstrate the potential of TestDose. A clinical imaging protocol for the Octreoscan™ therapeutical treatment was implemented using the 4D XCAT model. Whole-body “step and shoot” acquisitions at different times postinjection and one SPECT acquisition were generated within reasonable computation times. Based on the same Octreoscan™ kinetics, a dosimetry

  11. ABT-773: pharmacokinetics and interactions with ranitidine and sucralfate.

    Science.gov (United States)

    Pletz, M W; Preechachatchaval, V; Bulitta, J; Allewelt, M; Burkhardt, O; Lode, H

    2003-03-01

    We assessed the pharmacokinetics and interaction of ABT-773 in 12 volunteers receiving ABT-773 alone or concomitantly with ranitidine or sucralfate. Data for 150 mg of ABT-773 were as follows: the maximum concentration of the drug in plasma (C(max)) was 318 ng/ml, its half-life was 5.66 h, and its area under the plasma concentration-time curve from 0 h to infinity (AUC(0- infinity )) was 1,662 ng. h/ml. Coadministration of ranitidine, reduced the C(max) (-25.7%) and AUC(0- infinity ) (-15.8%) significantly. Sucralfate had no impact on the bioavailability of ABT-773.

  12. Population pharmacokinetics of ifosfamide and its 2-and 3-dechloroethylated and 4-hydroxylated metabolites in resistant small-cell lung cancer patients

    NARCIS (Netherlands)

    Kerbusch, T; vanPutten, JWG; Groen, HJM; Huitema, ADR; Mathot, RAA; Beijnen, JH

    The aim of this study was to develop a population pharmacokinetic model that could describe the pharmacokinetics of ifosfamide, 2- and 3-dechloroethylifosfamide and 4-hydroxyifosfamide, and calculate their plasma exposure and urinary excretion. A group of 14 patients with small-cell lung cancer

  13. Population pharmacokinetic model of transdermal nicotine delivered from a matrix-type patch.

    Science.gov (United States)

    Linakis, Matthew W; Rower, Joseph E; Roberts, Jessica K; Miller, Eleanor I; Wilkins, Diana G; Sherwin, Catherine M T

    2017-12-01

    Nicotine addiction is an issue faced by millions of individuals worldwide. As a result, nicotine replacement therapies, such as transdermal nicotine patches, have become widely distributed and used. While the pharmacokinetics of transdermal nicotine have been extensively described using noncompartmental methods, there are few data available describing the between-subject variability in transdermal nicotine pharmacokinetics. The aim of this investigation was to use population pharmacokinetic techniques to describe this variability, particularly as it pertains to the absorption of nicotine from the transdermal patch. A population pharmacokinetic parent-metabolite model was developed using plasma concentrations from 25 participants treated with transdermal nicotine. Covariates tested in this model included: body weight, body mass index, body surface area (calculated using the Mosteller equation) and sex. Nicotine pharmacokinetics were best described with a one-compartment model with absorption based on a Weibull distribution and first-order elimination and a single compartment for the major metabolite, cotinine. Body weight was a significant covariate on apparent volume of distribution of nicotine (exponential scaling factor 1.42). After the inclusion of body weight in the model, no other covariates were significant. This is the first population pharmacokinetic model to describe the absorption and disposition of transdermal nicotine and its metabolism to cotinine and the pharmacokinetic variability between individuals who were administered the patch. © 2017 The British Pharmacological Society.

  14. Pharmacokinetic study of gallocatechin-7-gallate from Pithecellobium clypearia Benth. in rats

    Directory of Open Access Journals (Sweden)

    Chao Li

    2016-01-01

    Full Text Available The pharmacokinetic profile of gallocatechin-7-gallate (J10688 was studied in rats after intravenous administration. Male and female Sprague-Dawley (SD rats received 1, 3, and 10 mg/kg (i.v. of J10688 and plasma drug concentrations were determined by a high performance liquid chromatography-mass spectrometry (LC–MS method. The pharmacokinetic software Data Analysis System (Version 3.0 was used to calculate the pharmacokinetic parameters. For different i.v. doses of J10688, the mean peak plasma concentration (C0 values ranged from 11.26 to 50.82 mg/L, and mean area under the concentration-time curve (AUC0–t values ranged from 1.75 to 11.80 (mg·h/L. J10688 lacked dose-dependent pharmacokinetic properties within doses between 1 and 10 mg/kg, based on the power model. The method developed in this study was sensitive, precise, and stable. The pharmacokinetic properties of J10688 in SD rats were shown to have rapid distribution and clearance values. These pharmacokinetic results may contribute to an improved understanding of the pharmacological actions of J10688.

  15. Pharmacokinetic interaction between scutellarin and valsartan in rats.

    Science.gov (United States)

    Cui, Ming-Yu; Tian, Chong-Chong; Ju, Ai-Xia; Zhang, Chun-Ting; Li, Qiu-Hong

    2013-04-01

    Scutellarin is the main effective constituent of breviscapine, a flavonoid mixture isolated from the dried whole plant of Erigeron breviscapus (Vant.) Hand-Mazz, and valsartan is used as an antihypertensive drug. These two drugs have already been clinically used together to treat diabetic nephropathy (DN) in China, and the combined medications showed some enhanced protection against DN. The aim of this study is to investigate the potential pharmacokinetic interaction between scutellarin and valsartan in rats. Breviscapine injection (20 mg x kg(-1), i.v.) and valsartan (15 mg x kg-, i.g.), either alone or together were given to 18 male Sprague-Dawley rats. Concentrations of scutellarin and valsartan were quantified by HPLC, and pharmacokinetic parameters were calculated by non-compartmental methods. We found that the pharmacokinetic parameters of scutellarin altered significantly after co-administration of oral valsartan. The plasma clearance (CL(p)) and the bile clearance (CL(b)) of scutellarin were reduced significantly in the presence of valsartan. After oral administration of valsartan with or without intravenous scutellarin, however, the pharmacokinetic parameters of valsartan were comparable. In conclusion, our data suggests that the concurrent use of valsartan reduces the biliary excretion of scutellarin, and this may be due to the inhibitory effect of valsartan on the biliary excretion of scutellarin mediated by Mrp2 (Multidrug resistance-associated protein 2).

  16. Portal dosimetry in wedged beams

    NARCIS (Netherlands)

    Spreeuw, Hanno; Rozendaal, Roel; Camargo, Priscilla; Mans, Anton; Wendling, Markus; Olaciregui-Ruiz, Igor; Sonk