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Sample records for oral antidiabetic drugs

  1. Pharmacogenetics of oral antidiabetic drugs

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    M.L. Becker (Matthijs); E. Pearson (Ewan); I. Tkáč (Ivan)

    2013-01-01

    textabstractOral antidiabetic drugs (OADs) are used for more than a half-century in the treatment of type 2 diabetes. Only in the last five years, intensive research has been conducted in the pharmacogenetics of these drugs based mainly on the retrospective register studies, but only a handful of as

  2. Pharmacogenetics of Oral Antidiabetic Drugs

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    Matthijs L. Becker

    2013-01-01

    Full Text Available Oral antidiabetic drugs (OADs are used for more than a half-century in the treatment of type 2 diabetes. Only in the last five years, intensive research has been conducted in the pharmacogenetics of these drugs based mainly on the retrospective register studies, but only a handful of associations detected in these studies were replicated. The gene variants in CYP2C9, ABCC8/KCNJ11, and TCF7L2 were associated with the effect of sulfonylureas. CYP2C9 encodes sulfonylurea metabolizing cytochrome P450 isoenzyme 2C9, ABCC8 and KCNJ11 genes encode proteins constituting ATP-sensitive K+ channel which is a therapeutic target for sulfonylureas, and TCF7L2 is a gene with the strongest association with type 2 diabetes. SLC22A1, SLC47A1, and ATM gene variants were repeatedly associated with the response to metformin. SLC22A1 and SLC47A1 encode metformin transporters OCT1 and MATE1, respectively. The function of a gene variant near ATM gene identified by a genome-wide association study is not elucidated so far. The first variant associated with the response to gliptins is a polymorphism in the proximity of CTRB1/2 gene which encodes chymotrypsinogen. Establishment of diabetes pharmacogenetics consortia and reduction in costs of genomics might lead to some significant clinical breakthroughs in this field in a near future.

  3. Transporter-Mediated Drug–Drug Interactions with Oral Antidiabetic Drugs

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    Jörg König

    2011-10-01

    Full Text Available Uptake transporters (e.g., members of the SLC superfamily of solute carriers and export proteins (e.g., members of the ABC transporter superfamily are important determinants for the pharmacokinetics of drugs. Alterations of drug transport due to concomitantly administered drugs that interfere with drug transport may alter the kinetics of drug substrates. In vitro and in vivo studies indicate that many drugs used for the treatment of metabolic disorders and cardiovascular diseases (e.g., oral antidiabetic drugs, statins are substrates for uptake transporters and export proteins expressed in the intestine, the liver and the kidney. Since most patients with type 2 diabetes receive more than one drug, transporter-mediated drug-drug interactions are important molecular mechanisms leading to alterations in oral antidiabetic drug pharmacokinetics with the risk of adverse drug reactions. This review focuses on uptake transporters of the SLCO/SLC21 (OATP and SLC22 (OCT/OAT family of solute carriers and export pumps of the ABC (ATP-binding cassette transporter superfamily (especially P-glycoprotein as well as the export proteins of the SLC47 (MATE family and their role for transporter-mediated drug-drug interactions with oral antidiabetic drugs.

  4. Pharmacogenomics in type 2 diabetes: oral antidiabetic drugs.

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    Daniels, M A; Kan, C; Willmes, D M; Ismail, K; Pistrosch, F; Hopkins, D; Mingrone, G; Bornstein, S R; Birkenfeld, A L

    2016-10-01

    Type 2 diabetes mellitus (T2DM) is a fast progressing disease reaching pandemic proportions. T2DM is specifically harmful because of its severe secondary complications. In the course of the disease, most patients require treatment with oral antidiabetic drugs (OADs), for which a relatively large number of different options are available. The growing number of individuals affected by T2DM as well as marked interindividual differences in the response to treatment call for individualized therapeutic regimens that can maximize treatment efficacy and thus reduce side effects and costs. A large number of genetic polymorphisms have been described affecting the response to treatment with OADs; in this review, we summarize the most recent advances in this area of research. Extensive evidence exists for polymorphisms affecting pharmacokinetics and pharmacodynamics of biguanides and sulfonylureas. Data on incretin-based medications as well as the new class of sodium/glucose cotransporter 2 (SGLT2) inhibitors are just starting to emerge. With diabetes being a known comorbidity of several psychiatric disorders, we also review genetic polymorphisms possibly responsible for a common treatment response in both conditions. For all drug classes reviewed here, large prospective trials are necessary in order to consolidate the existing evidence and derive treatment schemes based on individual genetic traits.

  5. Racial differences in long-term adherence to oral antidiabetic drug therapy: a longitudinal cohort study

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    Meigs James B

    2009-02-01

    Full Text Available Abstract Background Adherence to oral antidiabetic medications is often suboptimal. Adherence differences may contribute to health disparities for black diabetes patients, including higher microvascular event rates, greater complication-related disability, and earlier mortality. Methods In this longitudinal retrospective cohort study, we used 10 years of patient-level claims and electronic medical record data (1/1/1992–12/31/2001 to assess differences in short- and long-term adherence to oral antidiabetic medication among 1906 newly diagnosed adults with diabetes (26% black, 74% white in a managed care setting in which all members have prescription drug coverage. Four main outcome measures included: (1 time from diabetes diagnosis until first prescription of oral antidiabetic medication; (2 primary adherence (time from first prescription to prescription fill; (3 time until discontinuation of oral antidiabetic medication from first prescription; and (4 long-term adherence (amount dispensed versus amount prescribed over a 24-month follow-up from first oral antidiabetic medication prescription. Results Black patients were as likely as whites to initiate oral therapy and fill their first prescription, but experienced higher rates of medication discontinuation (HR: 1.8, 95% CI: 1.2, 2.7 and were less adherent over time. These black-white differences increased over the first six months of therapy but stabilized thereafter for patients who initiated on sulfonylureas. Significant black-white differences in adherence levels were constant throughout follow-up for patients initiated on metformin therapy. Conclusion Racial differences in adherence to oral antidiabetic drug therapy persist even with equal access to medication. Early and continued emphasis on adherence from initiation of therapy may reduce persistent racial differences in medication use and clinical outcomes.

  6. Adding liraglutide to oral antidiabetic drug therapy: onset of treatment effects over time

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    Gallwitz, B; Vaag, A; Falahati, A;

    2010-01-01

    AIM: To investigate the onset of treatment effects over time observed for liraglutide in combination with oral antidiabetic drugs (OADs). METHODS: This analysis included patients from three phase 3, 26-week, randomised, double-blind, parallel-group trials. Prior to randomisation, patients underwent...

  7. Cost analysis study of oral antidiabetic drugs available in Indian market

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    Nisharani B Jadhav, Manisha S Bhosale, Charles V Adhav

    2013-01-01

    Full Text Available There exists a wide range of variation in the prices of drugs marketed in India and other countries of the world. Very few studies have been conducted to reveal such price variations in the open market. Aim & Objectives: To evaluate the cost of oral anti-diabetics of different generic classes and different brand names of one compound, To evaluate the difference in cost of different brands for the same active drug by calculating percentage variation of cost. Methods: Cost of a particular drug being manufactured by different companies, in the same strength, number and dosage form was compared. The difference in the maximum and minimum price of the same drug manufactured by different pharmaceutical companies and the percentage variation in price was calculated. Results: In Single drug therapy, among sulfonylurea group of drugs, Glimepiride (1 mg shows maximum price variation of 655.38%, while Glipizide (10mg shows variation of 38.88%. In Biguanides & Thizolidinediones groups of drugs, Metformin (500 mg & Pioglitazone (15 mg show maximum price variation of 308.33% & 542% respectively. In α-glucosidases inhibitor group of drugs, Miglitol shows maximum price variation of 135.50 %. In combination therapies, Glipizide & Metformin combination shows the maximum variation up to 399.04 %. Conclusion: The average percentage price variation of different brands of the same drug manufactured in India is very wide and the appraisal and management of marketing drugs should be directed toward maximizing the benefits of therapy and minimizing negative personal and economic consequences

  8. Adherence to oral anti-diabetic drugs among patients attending a Ghanaian teaching hospital

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    Bruce SP

    2015-03-01

    Full Text Available Background: The burden of diabetes mellitus, especially Type-2, continues to increase across the world. Medication adherence is considered an integral component in its management. Poor glycemic controls due to medication nonadherence accelerates the development of long-term complications which consequently leads to increased hospitalization and mortality. Objective: This study examined the level of adherence to oral antidiabetic drugs among patients who visited the teaching hospital and explored the probable contributory factors to non-adherence. Methods: A cross-sectional descriptive study using systematic sampling to collect quantitative data was undertaken. Questionnaires were administered to out-patients of the medical department of a teaching hospital in Ghana. Logistic regression was performed with statistical significance determined at p<0.05. Results: A total of 200 diabetic patients participated in the study. Using the Morisky Medication Adherence scale, the level of adherence determined was 38.5%. There were significant correlations between level of adherence and educational level [(OR=1.508; (CI 0.805- 2.825, P=0.019, and mode of payment [(OR=1.631; (CI 0.997- 2.669, P=0.05. Conclusion: Adherence in diabetic patients was low among respondents and this can be improved through education, counseling and reinforcement of self-care. There were several possible factors that contributed to the low adherence rate which could benefit from further studies.

  9. Oral antidiabetic therapy in a large Italian sample: drug supply and compliance for different therapeutic regimens

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    Vittorino Gaddi, A; Capello, F; Di Pietro, C; Cinconze, E; Rossi, E; De Sando, V; Cevenini, M; D'Alò, G

    2014-01-01

    Objectives: To define the main features of patients treated with oral antidiabetics, evaluating monotherapy (MT), loose-dose combination therapy (LDCT) and fixed-dose combination therapy (FDCT); to describe medication adherence to the different therapies; and to evaluate the differences in compliance with the prescribed therapy regimen among prevalent and incident patient cohorts. Study design: This study was a retrospective cohort analysis based on the ARNO database, a national record that tracks reimbursable prescription claims submitted from selected pharmacies to the Italian national health system. In total, 169,375 subjects, from an overall population of 4,040,624 were included in this study. The patients represented 12 different local health units. Each patient had at least one oral antidiabetic prescription claim (A10B ATC code). Methods: Patients were divided into four groups according to their treatment regimen during the recruitment period (1 January 2008-31 December 2008): MT, FDCT, LDCT and swi...

  10. Association of PAX4 genetic variants with oral antidiabetic drugs efficacy in Chinese type 2 diabetes patients.

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    Chen, M; Hu, C; Zhang, R; Jiang, F; Wang, J; Peng, D; Tang, S; Sun, X; Yan, J; Luo, Y; Bao, Y; Jia, W

    2014-10-01

    The aim of this study was to investigate the association of PAX4 variants with therapeutic effect of oral antidiabetic drugs in Chinese type 2 diabtes mellitus (T2DM) patients. A total of 209 newly diagnosed T2DM patients were randomly assigned to treatment with repaglinide or rosiglitazone for 48 weeks, and the therapeutic effects were compared. In the rosiglitazone cohort, rs6467136 GA+AA carriers showed greater decrease in 2-h glucose levels (P=0.0063) and higher cumulative attainment rates of target 2-h glucose levels (Plog rank=0.0093) than GG homozygotes. In the subgroup with defective β-cell function, rs6467136 GA+AA carriers exhibited greater decrements of 2-h glucose level and improvement of homeostasis model assessment of insulin resistance (P=0.0143). Moreover, GA+AA carriers were more likely to attain the target fasting and 2-h glucose level (Plog rank=0.0091 and 0.007, respectively). However, these single-nucleotide polymorphisms showed no effect on repaglinide efficacy. In conclusion, PAX4 variant rs6467136 was associated with the therapeutic effect of rosiglitazone in Chinese T2DM patients.

  11. Hypoglycaemia with oral antidiabetic drugs: results from prescription-event monitoring cohorts of rosiglitazone, pioglitazone, nateglinide and repaglinide.

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    Vlckova, Veronika; Cornelius, Victoria; Kasliwal, Rachna; Wilton, Lynda; Shakir, Saad A W

    2009-01-01

    Hypoglycaemia is an acute complication associated with intensive treatment of patients with diabetes mellitus. This complication poses a major challenge in diabetes management. Furthermore, severe hypoglycaemia may be life threatening. Although hypoglycaemia is more often associated with insulin treatment, oral hypoglycaemic agents have the potential to trigger hypoglycaemia. The aim of this study was to quantify the incidence of hypoglycaemic events and to describe the pattern of these incident events during the first 9 months of treatment with four oral antidiabetic drugs, rosiglitazone, pioglitazone, nateglinide and repaglinide, prescribed in general practice in England. We used data collected for prescription-event monitoring (PEM) studies of rosiglitazone, pioglitazone, nateglinide and repaglinide. PEM is an observational, non-interventional, incept cohort study. Observation time for each patient and incidence rate (IR) per 1000 patient-years of treatment for hypoglycaemia was calculated for each drug cohort. Smoothed hazard estimates were plotted over time. Case/non-case analysis was performed to describe and compare patients who had at least one hypoglycaemic event in the first 9 months of treatment with those who did not. The total number of patients included in the analysis was 14,373, 12,768, 4,549 and 5,727 in rosiglitazone, pioglitazone, nateglinide and repaglinide cohorts, respectively. From these, 276 patients experienced at least one episode of hypoglycaemia. The IR was between 50% and 100% higher in patients receiving treatment with meglitinides compared with those treated with the thiazolidinediones (TZDs) [IR = 9.94, 9.64, 15.71 and 20.32 per 1,000 patient-years for rosiglitazone, pioglitazone, nateglinide and repaglinide, respectively]. The plot of the hazard function and the estimated shape parameter from the Weibull regression model showed that pioglitazone, nateglinide and repaglinide had non-constant (decreasing) hazards over time, whereas

  12. Efficacy and safety of oral antidiabetic drugs in comparison to insulin in treating gestational diabetes mellitus: a meta-analysis.

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    Nalinee Poolsup

    Full Text Available OBJECTIVE: To assess the efficacy and safety of oral antidiabetic drugs (OADs in gestational diabetes mellitus (GDM in comparison to insulin. METHODS: A meta-analysis of randomized controlled trials was conducted. The efficacy and safety of OADs in comparison to insulin in GDM patients were explored. Studies were identified by conducting a literature search using the electronic databases of Medline, CENTRAL, CINAHL, LILACS, Scopus and Web of Science in addition to conducting hand search of relevant journals from inception until October 2013. RESULTS: Thirteen studies involving 2,151 patients met the inclusion criteria. These studies were randomized controlled trials of metformin and glyburide in comparison to insulin therapy. Our results indicated a significant increase in the risk for preterm births (RR, 1.51; 95% CI, 1.04-2.19, p = 0.03 with metformin compared to insulin. However, a significant decrease in the risk for gestational hypertension (RR, 0.54; 95% CI, 0.31-0.91, p = 0.02 was found. Postprandial glucose levels also decreased significantly in patients receiving metformin (MD, -2.47 mg/dL; 95% CI, -4.00, -0.94, p = 0.002. There was no significant difference between the two groups for the remaining outcomes. There were significant increases in the risks of macrosomia (RR, 2.34; 95% CI, 1.18-4.63, p = 0.03 and neonatal hypoglycemia (RR, 2.06; 95% CI, 1.27-3.34, p = 0.005 in the glyburide group compared to insulin whereas results for the other analyzed outcomes remained non-significant. CONCLUSION: The available evidence suggests favorable effects of metformin in treating GDM patients. Metformin seems to be an efficacious alternative to insulin and a better choice than glyburide especially those with mild form of disease.

  13. The Novel Oral Drug Subetta Exerts an Antidiabetic Effect in the Diabetic Goto-Kakizaki Rat: Comparison with Rosiglitazone

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    Bailbé, Danielle; Portha, Bernard

    2013-01-01

    The aim of the present study was to evaluate the potential antidiabetic effects of two-component drug Subetta and its components (release-active dilutions of antibodies to β-subunit insulin receptor (RAD of Abs to β-InsR) and to endothelial nitric oxide synthase (RAD of Abs to eNOS)) in Goto-Kakizaki (Paris colony) (GK/Par) diabetic rats. Subetta was administered orally for 28 days once daily (5 mL/kg) and compared to its two components (2.5 mL/kg), Rosiglitazone (5 mg/kg), and vehicle (5 mL water/kg). At day 28, fasting plasma glucose levels were significantly decreased only in Subetta and Rosiglitazone groups as compared to vehicle (P < 0.01): 147 ± 4 mg/dL and 145 ± 4 mg/dL and 165 ± 4 mg/dL, respectively. The data of glucose tolerance test showed that Subetta and RAD of Abs to β-InsR (similar to Rosiglitazone) prevented significantly (P < 0.01) the age-related spontaneous deterioration of glucose tolerance as seen in the control group. Subetta and RAD of Abs to β-InsR did not significantly modify the glucose-induced insulin secretion. Chronic administration of Subetta and RAD of Abs to β-InsR improves glucose control, to an extent similar to that of Rosiglitazone. We hypothesize that Subetta and RAD of Abs to β-InsR mostly act via an insulin-sensitizing effect upon target tissues. PMID:23762875

  14. EXPERIENCE WITH THE ROSINSULIN C IN COMBINATION WITH ORAL ANTIDIABETIC DRUGS IN PATIENTS WITH TYPE 2 DIABETES IN ROUTINE CLINICAL PRACTICE

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    O. D. Rymar

    2014-01-01

    Full Text Available This study aimed to estimate the efficacy and safety of intermediate-acting insulin Rosinsulin C in patients with type 2 diabetes mellitus inadequately controlled with oral antidiabetic drugs.The present study is a 6-month, prospective, uncontrolled, clinical experience evaluation study using insulin Rosinsulin С for type 2 diabetes patients in daily clinical practice. Episodes of hypoglycaemia, adverse events were recorded. The study included 28 patients with type 2 diabetes, 4 men and 24 women who treated with metformin in combination with sulfonylureas in the highest dose. Indicators of glycosylated hemoglobin (HbA1c of 8 to 14%, the median HbA1c was 11 (10; 13% of patients age 65 (57; 72 years, body mass index – 33 (30; 35 kg/m2, waist circumference – 105 (99; 111 cm, diabetes duration – 7 (2; 11 years. With the introduction of Rosinsulin С cartridges carried pen Autopen. At the start of the study and after 3 and 6 months, determined the level of HbA1c, fasting plasma glucose.After 6 months' treatment with Rosinsulin С in combination with oral antidiabetic drugs HbA1c was significantly lowered (–3% (p = 0,001, fasting plasma glucose level decreased by 5 mmol/L (p = 0,001. There was not severe hypoglycemia during the observation period.This research showed that Rosinsulin C is effective and safe in the treatment of patients with type 2 diabetes who were decompensated with oral antidiabetic drugs and can be recommended for use as the initiation of insulin therapy in routine clinical practice.

  15. Prescription factors associated with medication non-adherence in Japan assessed from leftover drugs in the SETSUYAKU-BAG campaign: Focus on oral antidiabetic drugs

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    Kaori Koyanagi

    2016-07-01

    Full Text Available Background: Medication adherence has an important influence on health outcomes in patients with chronic diseases. However, few studies have been performed in Japan to determine factors related to medication non-adherence. Objective: The aim of this study was to identify prescription factors related to medication non-adherence by investigating patient characteristics, all prescriptions, and prescriptions for oral antidiabetic drugs (OADs.Methods: A retrospective cross-sectional survey of prescription data about implementation of dosing regimen was performed at community pharmacies engaged in appropriate use of leftover drugs. We evaluated the amount of drugs originally prescribed and the reduced amount after use of leftover drugs, and then calculated prescription reduction ratio (PRR. We analyzed prescription factors contributing to non-adherence based on the PRR.Results: Prescription information for 1,207 patients was reviewed, revealing that patients were non-adherent to 58% of prescriptions. Lack of a drug copayment, fewer concurrent drugs, and drugs not in single-dose packaging were associated with non-adherence. Among the 1,207 patients, 234 prescriptions for diabetes and 452 OAD formulations were included. Forty-seven percent of prescriptions and 29% of the formulations were non-adherent. A higher dosing frequency and preprandial administration were associated with non-adherence. Among the OADs, adherence was lower for α-glucosidase inhibitors and biguanides than for sulfonylureas. Conclusions: Several factors related to patient characteristics, general drug prescriptions, and OAD prescriptions were associated with non-adherence. Further consideration will be needed to improve adherence to medication in Japan. Health care providers should perform more careful monitoring of adherence in patients with the factors identified by this study.

  16. Comparative genotoxic and cytotoxic effects of the oral antidiabetic drugs sitagliptin, rosiglitazone, and pioglitazone in patients with type-2 diabetes: a cross-sectional, observational pilot study.

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    Oz Gul, Ozen; Cinkilic, Nilufer; Gul, Cuma Bulent; Cander, Soner; Vatan, Ozgur; Ersoy, Canan; Yılmaz, Dilek; Tuncel, Ercan

    2013-09-18

    This cross-sectional, observational pilot study was designed to investigate the frequency of different endpoints of genotoxicity (sister-chromatid exchange, total chromosome aberrations, and micronucleus formation) and cytotoxicity (mitotic index, replication index, and nuclear division index) in the peripheral lymphocytes of patients with type-2 diabetes treated with different oral anti-diabetic agents for 6 months. A total of 104 patients who met the American Diabetes Association criteria for type-2 diabetes were enrolled in the study. Of the 104 patients, 33 were being treated with sitagliptin (100mg/day), 25 with pioglitazone (30mg/day), 22 with rosiglitazone (4mg/day), and 24 with medical nutrition therapy (control group). The results for all the genotoxicity endpoints were significantly different across the four study groups. Post hoc analysis revealed that the genotoxicity observed in the sitagliptin group was significantly higher than that observed in the medical nutrition therapy group, but lower than that occurring in subjects who received thiazolidinediones. All of the three cytotoxicity endpoints were significantly lower in patients treated by oral anti-diabetic agents compared with those who received medical nutrition therapy. However, the three indexes did not differ significantly in the sitagliptin, rosiglitazone, and pioglitazone groups. Taken together, these pilot data indicate that sitagliptin and thiazolidinediones may exert genotoxic and cytotoxic effects in patients with type-2 diabetes. Further investigations are necessary to clarify the possible long-term differences between oral anti-diabetic drugs in terms of genotoxicity and cytotoxicity, and how these can modulate the risk of developing diabetic complications in general and cancer in particular.

  17. Magnetic solid-phase extraction based on mesoporous silica-coated magnetic nanoparticles for analysis of oral antidiabetic drugs in human plasma.

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    de Souza, Karynne Cristina; Andrade, Gracielle Ferreira; Vasconcelos, Ingrid; de Oliveira Viana, Iara Maíra; Fernandes, Christian; de Sousa, Edésia Martins Barros

    2014-07-01

    In the present work, magnetic nanoparticles embedded into mesoporous silica were prepared in two steps: first, magnetite was synthesized by oxidation-precipitation method, and next, the magnetic nanoparticles were coated with mesoporous silica by using nonionic block copolymer surfactants as structure-directing agents. The mesoporous SiO2-coated Fe3O4 samples were functionalized using octadecyltrimethoxysilane as silanizing agent. The pure and functionalized silica nanoparticles were physicochemically and morphologically characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), N2 adsorption, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The resultant magnetic silica nanoparticles were applied as sorbents for magnetic solid-phase extraction (MSPE) of oral antidiabetic drugs in human plasma. Our results revealed that the magnetite nanoparticles were completely coated by well-ordered mesoporous silica with free pores and stable pore walls, and that the structural and magnetic properties of the Fe3O4 nanoparticles were preserved in the applied synthesis route. Indeed, the sorbent material was capable of extracting the antidiabetic drugs from human plasma, being useful for the sample preparation in biological matrices.

  18. Comparative evaluation of effects of combined oral anti-diabetic drugs (sulfonylurea plus pioglitazone and sulfonylurea plus metformin over lipid parameters in type 2 diabetic patients

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    Sukanta Sen

    2013-06-01

    Full Text Available Background: Type 2 diabetes is associated with significant cardiovascular morbidity and mortality. Dyslipidemia, which affects almost 50% of patients with type 2 diabetes, is a cardiovascular risk factor characterized by elevated triglyceride levels, low high-density lipoprotein (HDL cholesterol levels, and a preponderance of small, dense, low-density lipoprotein (LDL particles. In addition to their glucose-lowering properties, oral anti-diabetic agents may have effects on lipid levels, especially triglycerides (TGs, HDL-C, LDL-C and total cholesterol levels. Methods: A prospective, open-labeled, randomized, parallel-group study was carried out in sizable number of patients (n=40 of established type 2 diabetes on combined oral anti-diabetic drugs, to investigate the effects of combined oral anti-diabetic on lipid parameters who was not receiving any hypolipidemic agent in addition. Results: Statistically significant mean reduction of triglycerides (TGs of 25.1mg/dl (a 15.30% reduction from baseline value and by 13.5 mg/dl (a 8.94% reduction from baseline value in the SU (sulfonylurea plus PIO (pioglitazone and SU plus MET (metformin group respectively. Present study also shows improvement in HDL cholesterol with SU plus PIO group by 13.18% which is almost twice that observed in SU plus MET group (8.06%. Present study also shows increase in LDL cholesterol with SU plus PIO group by 2.10%, is just opposite to SU plus MET group (4.92 % decrease. With SU plus PIO group, a statistically significant mean reduction of total cholesterol (TC of 8.33mg/dl (5.14 % decrease and by 7.62 mg/dl (4.28% decrease in the SU plus MET group. Conclusions: Pioglitazone, a thiazolidinedione, has been shown to improve the lipid profile in patients with type 2 diabetes by increasing HDL-C levels and by decreasing triglyceride and total cholesterol levels in monotherapy or combination regimens with sulfonylurea. Metformin also has been shown to reduce LDL-C, TC, and TG

  19. Magnetic solid-phase extraction based on mesoporous silica-coated magnetic nanoparticles for analysis of oral antidiabetic drugs in human plasma

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    Souza, Karynne Cristina de; Andrade, Gracielle Ferreira [Centro de Desenvolvimento da Tecnologia Nuclear, CDTN/CNEN, Rua Professor Mário Werneck, s/n. Campus Universitário, Belo Horizonte, MG CEP 30.123-970 (Brazil); Vasconcelos, Ingrid; Oliveira Viana, Iara Maíra de; Fernandes, Christian [Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Martins Barros de Sousa, Edésia, E-mail: sousaem@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear, CDTN/CNEN, Rua Professor Mário Werneck, s/n. Campus Universitário, Belo Horizonte, MG CEP 30.123-970 (Brazil)

    2014-07-01

    In the present work, magnetic nanoparticles embedded into mesoporous silica were prepared in two steps: first, magnetite was synthesized by oxidation–precipitation method, and next, the magnetic nanoparticles were coated with mesoporous silica by using nonionic block copolymer surfactants as structure-directing agents. The mesoporous SiO{sub 2}-coated Fe{sub 3}O{sub 4} samples were functionalized using octadecyltrimethoxysilane as silanizing agent. The pure and functionalized silica nanoparticles were physicochemically and morphologically characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), N{sub 2} adsorption, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The resultant magnetic silica nanoparticles were applied as sorbents for magnetic solid-phase extraction (MSPE) of oral antidiabetic drugs in human plasma. Our results revealed that the magnetite nanoparticles were completely coated by well-ordered mesoporous silica with free pores and stable pore walls, and that the structural and magnetic properties of the Fe{sub 3}O{sub 4} nanoparticles were preserved in the applied synthesis route. Indeed, the sorbent material was capable of extracting the antidiabetic drugs from human plasma, being useful for the sample preparation in biological matrices. - Highlights: • SBA-15/Fe{sub 3}O{sub 4} was synthesized and functionalized with octadecyltrimethoxysilane. • Magnetite nanoparticles were completely coated by well-ordered mesoporous silica. • The samples were used as sorbent for magnetic solid-phase extraction (MSPE). • The sorbent material was capable of extracting drugs from human plasma. • The extraction ability makes the material a candidate to be employed as MSPE.

  20. Incidence of potential drug-drug interactions with antidiabetic drugs.

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    Samardzic, I; Bacic-Vrca, V

    2015-06-01

    In an effort to achieve normoglycemia more than one antidiabetic agent is usually needed. Diabetes is associated with several comorbidities and patients with diabetes are often treated with multiple medications. Therefore, patients with diabetes are especially exposed to drug-drug interactions (DDIs). The aim of this study was to analyse the incidence and type of potential DDIs of antidiabetic drugs in patients with diabetes. This retrospective study analyzed pharmacy record data of 225 patients with diabetes mellitus. Both type 1 and type 2 diabetic patients who were taking at least one antidiabetic agent during the period of six months were included. We investigated associated therapy in that period in order to identify potential DDIs with antidiabetic therapy. Potential interactions were identified by Lexicomp Lexi-Interat Online (Lexi-Comp, Inc., Hudson, USA) software which categorizes potential DDIs according to clinical significance in five types (A, B, C, D and X). Categories C, D and X are of clinical concern and always require medical attention (therapy monitoring, therapy modification or avoiding combination). We found that 80.9% of patients had at least one potential category C interaction while there were no D and X interactions. Most frequently encountered potential DDI (n = 176) included antidiabetic drugs and thiazide or thiazide like diuretics. Patients with diabetes are exposed to a large number of potential clinically significant DDIs that may require appropriate monitoring. Using databases of DDIs could be helpful in reducing the risk of potential clinically significant DDIs.

  1. Antidiabetic drugs and risk of cancer.

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    Tokajuk, Anna; Krzyżanowska-Grycel, Edyta; Tokajuk, Adrian; Grycel, Sławomir; Sadowska, Anna; Car, Halina

    2015-12-01

    Antidiabetic drugs are an important group of medications used worldwide. They differ from each other in the mechanisms of lowering blood glucose as well as in adverse effects that may affect the course of the treatment and its efficacy. In recent years, new drugs have been discovered in order to improve the maintenance of proper blood glucose level and to reduce unwanted effects of these drugs. Their growing administration is related to the increasing incidence of diabetes observed in all countries in the world. Epidemiological data indicate that diabetes increases the risk of cancer, as well as the risk of death linked with neoplasms. It is still unknown whether this is an effect of antidiabetic drugs or just the effect of diabetes itself. In recent years there have been numerous investigations and meta-analyzes, based on both comparative and cohort studies trying to establish the relationship between antidiabetic pharmacotherapy and the incidence and mortality due to cancer. According to their findings, most of antidiabetic drugs increase the risk of cancer while only few of them show antitumor properties. Different mechanisms of action of glucose-lowering drugs may be responsible for these effects. However, most of the published studies concerning the influence of these drugs on cancer incidence were designed with some limitations and differed from each other in the approach. In this review, we discuss the association between antidiabetic drugs used in monotherapy or polytherapy and cancer risk, and consider potential mechanisms responsible for the observed effects. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  2. Impact of rosiglitazone safety alerts on oral antidiabetic sales trends: a countrywide study in Portugal.

    Science.gov (United States)

    Herdeiro, Maria T; Soares, Sara; Silva, Tânia; Roque, Fátima; Figueiras, Adolfo

    2016-10-01

    Pharmacovigilance systems are important to monitor the safety of on-market drugs after approval. The aim of this study was to assess the impact of rosiglitazone safety alerts on trends in the sale of rosiglitazone and other oral antidiabetic drugs. An ecological study was conducted, using temporally aggregated data and linking safety alerts to countrywide sales of all oral antidiabetic drugs in Portugal from January 2002 to December 2012. Sales figures for oral antidiabetic drugs marketed in Portugal were supplied by IMS Health Portugal with a breakdown by active substance and fixed combinations. The number of defined daily doses per 1000 inhabitants per day (DIDs) of each oral antidiabetic drug sold to the estimated diabetic population using oral antidiabetic drugs in Portugal was calculated. Particular attention was paid to the case of rosiglitazone, with the results being adjusted for changes in rosiglitazone reimbursement policies. A total of four safety alerts were issued about rosiglitazone. Rosiglitazone sales registered an increase of 32.9% (0.202 DIDs; P sales fell. Following the January 2006 and January 2008 safety alerts, rosiglitazone sales described a long-term downward trend, with decreases of 3.75% (-0023 DIDs; P > 0.05) and 0.24% (-0.001 DIDs; P > 0.05), respectively. It is important to promote the dissemination and publication of drug safety alerts. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  3. Drug utilization pattern of antidiabetic agents in a tertiary care hospital of western Odisha, India

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    Ratna Agrawal

    2016-10-01

    Conclusions: The prescribing trend has been monotherapy with insulin followed by oral antidiabetic drugs in the form of glimepiride and metformin combination. [Int J Basic Clin Pharmacol 2016; 5(5.000: 2222-2226

  4. Comparison of the influence of oral antidiabetic drug and combined with basal insulin treatment on diabetic control and micro-inflammatory state in type 2 diabetes mellitus patients

    Institute of Scientific and Technical Information of China (English)

    Gang Wu; Dong-Liang Liu; Xiang-Jun Li; Xiao-Yun Fan

    2016-01-01

    Objective:To investigate the influence of oral antidiabetic drug and combined with basal insulin treatment on diabetic control and micro-inflammatory state in type 2 diabetes mellitus patients.Methods:From May 2014 to June 2015, 128 cases of Type 2 diabetes mellitus were recruited and divided randomly into two groups as observation group and control group. The observation group was given metformin (Glucophage, 0.25 tid) plus basal insulin (glargine) treatment, while the control group was given metformin (Glucophage, initial dose of 0.25 tid; the largest total dose of 2 g) plus other non-euglycemic OADs necessarily for 6 months to adjust dose and control blood glucose at target. The diabetic control indexes, islet function and micro-inflammatory factors were detected and analyzed.Results:After 6 months of medication, the observation group showed significantly lower level of FPG, and HbA1cthan the control group. While AUCc-p, HOMA-β and HOMA-IR of the observation group showed significant difference compared to that of the control group after treatment. Also the micro-inflammatory indexes including hs-CRP, IGF-1, IL-6 and TNF-α of the observation group after treatment were significantly lower than the control group .Conclusions:Type 2 diabetes given metformin plus glargine not only could control and steady blood glucose, but also significant decrease the micro-inflammation state.

  5. Change of initial oral antidiabetic therapy in type 2 diabetic patients

    NARCIS (Netherlands)

    A. Plat (Arian); F.J.A. Penning-Van Beest (Fernie); S. Kessabi (Sophia); M.T. Groot (Martijn); R.M.C. Herings (Ron)

    2009-01-01

    textabstractObjective To explore the 'real-life' therapy of type 2 diabetes mellitus with oral antidiabetic drugs (OADs). Methods From the PHARMO Record Linkage System comprising linked drug dispensing and clinical laboratory data from approximately 2.5 million individuals in the Netherlands, among

  6. Rapid Acting Insulin Use and Persistence among Elderly Type 2 Diabetes Patients Adding RAI to Oral Antidiabetes Drug Regimens

    Science.gov (United States)

    Zhou, Steve; Fan, Tao

    2016-01-01

    We examined the real-world utilization and persistence of rapid acting insulin (RAI) in elderly patients with type 2 diabetes who added RAI to their drug (OAD) regimen. Insulin-naïve patients aged ≥65 years, with ≥1 OAD prescription during the baseline period, who were continuously enrolled in the US Humana Medicare Advantage insurance plan for 18 months and initiated RAI were included. Among patients with ≥2 RAI prescriptions (RAIp), persistence during the 12-month follow-up was assessed. Multivariate logistic regression analyses identified factors affecting RAI use and persistence. Of 3734 patients adding RAI to their OAD regimen, 2334 (62.5%) had a RAIp during follow-up. Factors associated with RAIp included using ≤2 OADs; cognitive impairment, basal insulin use during follow-up; and higher RAI out-of-pocket costs ($36 to <$56 versus $0 to $6.30). Patients were less likely to persist with RAI when on ≤2 OADs versus ≥3 OADs and when having higher RAI out-of-pocket costs ($36 to <$56 versus $0 to $6.30) and more likely to persist when they had cognitive impairment and basal insulin use during follow-up. Real-world persistence of RAI in insulin-naïve elderly patients with type 2 diabetes was very poor when RAI was added to an OAD regimen. PMID:27761472

  7. Determinants for inadequate glycaemic control in Chinese patients with mild-to-moderate type 2 diabetes on oral antidiabetic drugs alone

    Institute of Scientific and Technical Information of China (English)

    ZHANG Shao-ling; CHEN Zong-cun; YAN Li; CHEN Li-hong; CHENG Hua; JI Li-nong

    2011-01-01

    Background Prevalence of inadequate glycaemic control among patients with type 2 diabetes mellitus (T2DM)remains high. We assessed glycaemic control in the real-life practice among people with T2DM in metropolises in China who were treated with oral antidiabetic drugs (OAD) alone and to determine factors associated with inadequate giycaemic control in this population.Methods An observational, cross-sectional multicentre study was conducted in 16 metropolitan medical centers.People with T2DM who had been followed-up before the index visit which occurred from January to September 2007 were included in the study. All subjects were ≥30 years of age at the time of T2DM diagnosis and had received monotherapy or combination therapy of OAD for at least 6 months. Demographic and clinical data were collected from medical records. The main study outcome was the inadequate glucose control rate, which was calculated by the proportion of patients with haemoglobin A1c (HbA1c) ≥6.5% detected on the index visit.Results In this cohort of 455 patients with T2DM whose mean age was 60.6 years and mean disease duration was 6.1 years, 45.5% had inadequate glycaemic control. The mean (SD) HbA1c was 6.7% (1.3). Multivariate Logistic regression showed that physical inactivity, disease duration >10 years, body mass index (BMI) ≥24 kg/m2, low homeostasis model assessment of β-cell function (HOMA-β) index, less frequency of medical visit and hypertriglyceridaemia were independent determinants of inadequate glycaemic control. Higher incidence of self-reported hypoglycemia experience (47.1% vs. 34.8%, P=0.008) and more fear of hypoglycemia quantified by Worry subscaie of the Hypoglycaemia Fear Survey (HFS) Ⅱ were happened in subjects with good glycemic control.Conclusion Approximately one half of these outpatients with T2DM from the metropolitan medical centers in China had inadequate glycaemic control treated with OAD alone, which raises the need for more effective educational and

  8. Antidiabetic herbal drugs officially approved in China.

    Science.gov (United States)

    Jia, Wei; Gao, Wenyuan; Tang, Lida

    2003-12-01

    Over the centuries, Chinese herbal drugs have served as a major source of medicines for the prevention and treatment of diseases including diabetes mellitus (known as 'Xiao-ke'). It is estimated that more than 200 species of plants exhibit hypoglycaemic properties, including many common plants, such as pumpkin, wheat, celery, wax guard, lotus root and bitter melon. To date, hundreds of herbs and traditional Chinese medicine formulas have been reported to have been used for the treatment of diabetes mellitus. This paper provides a brief review of the antidiabetic drugs of plant origin that have been approved by the Chinese health regulatory agency for commercial use in China. It was believed, through pharmacological studies, that medicinal herbs were meticulously organized in these antidiabetic drug formulas such that polysaccharide containing herbs restore the functions of pancreatic tissues and cause an increase in insulin output by the functional beta cells, while other ingredients enhance the microcirculation, increase the availability of insulin and facilitate the metabolism in insulin-dependent processes. Pharmacological and clinical evaluations indicated that these drugs had a mild, but significant, blood glucose lowering effect and that the long-term use of these agents may be advantageous over chemical drugs in alleviating some of the chronic diseases and complications caused by diabetes. Additionally, the use of these natural agents in conjunction with conventional drug treatments, such as a chemical agent or insulin, permits the use of lower doses of the drug and/or decreased frequency of administration which decreases the side effects most commonly observed. Copyright 2003 John Wiley & Sons, Ltd.

  9. Newer antidiabetic drugs and calorie restriction mimicry

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    Sanjay Kalra

    2016-01-01

    Full Text Available De-acceleration of aging and delayed development of age-related morbidity accompanies the restriction of calories (without malnutrition in laboratory mice, nematodes, yeast, fish, and dogs. Recent results from long-term longitudinal studies conducted on primates have suggested longevity benefits of a 30% restriction of calories in rhesus monkeys as well. Among calorie restricted rhesus monkeys one of the mechanisms for the improvement in lifespan was the reduction in the development of glucose intolerance and cardiovascular disease. Although there are no comparable human studies, it is likely that metabolic and longevity benefits will accompany a reduction in calories in humans as well. However, considering the difficulties in getting healthy adults to limit food intake science has focused on understanding the biochemical processes that accompany calorie restriction (CR to formulate drugs that would mimic the effects of CR without the need to actually restrict calories. Drugs in this emerging therapeutic field are called CR mimetics. Some of the currently used anti-diabetic agents may have some CR mimetic like effects. This review focuses on the CR mimetic properties of the currently available anti-diabetic agents.

  10. Pharmacogenetics of Anti-Diabetes Drugs

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    Johanna K. DiStefano

    2010-08-01

    Full Text Available A variety of treatment modalities exist for individuals with type 2 diabetes mellitus (T2D. In addition to dietary and physical activity interventions, T2D is also treated pharmacologically with nine major classes of approved drugs. These medications include insulin and its analogues, sulfonylureas, biguanides, thiazolidinediones (TZDs, meglitinides, α-glucosidase inhibitors, amylin analogues, incretin hormone mimetics, and dipeptidyl peptidase 4 (DPP4 inhibitors. Pharmacological treatment strategies for T2D are typically based on efficacy, yet favorable responses to such therapeutics are oftentimes variable and difficult to predict. Characterization of drug response is expected to substantially enhance our ability to provide patients with the most effective treatment strategy given their individual backgrounds, yet pharmacogenetic study of diabetes medications is still in its infancy. To date, major pharmacogenetic studies have focused on response to sulfonylureas, biguanides, and TZDs. Here, we provide a comprehensive review of pharmacogenetics investigations of these specific anti-diabetes medications. We focus not only on the results of these studies, but also on how experimental design, study sample issues, and definition of ‘response’ can significantly impact our interpretation of findings. Understanding the pharmacogenetics of anti-diabetes medications will provide critical baseline information for the development and implementation of genetic screening into therapeutic decision making, and lay the foundation for “individualized medicine” for patients with T2D.

  11. Pharmacogenetics of Anti-Diabetes Drugs.

    Science.gov (United States)

    Distefano, Johanna K; Watanabe, Richard M

    2010-08-01

    A variety of treatment modalities exist for individuals with type 2 diabetes mellitus (T2D). In addition to dietary and physical activity interventions, T2D is also treated pharmacologically with nine major classes of approved drugs. These medications include insulin and its analogues, sulfonylureas, biguanides, thiazolidinediones (TZDs), meglitinides, α-glucosidase inhibitors, amylin analogues, incretin hormone mimetics, and dipeptidyl peptidase 4 (DPP4) inhibitors. Pharmacological treatment strategies for T2D are typically based on efficacy, yet favorable responses to such therapeutics are oftentimes variable and difficult to predict. Characterization of drug response is expected to substantially enhance our ability to provide patients with the most effective treatment strategy given their individual backgrounds, yet pharmacogenetic study of diabetes medications is still in its infancy. To date, major pharmacogenetic studies have focused on response to sulfonylureas, biguanides, and TZDs. Here, we provide a comprehensive review of pharmacogenetics investigations of these specific anti-diabetes medications. We focus not only on the results of these studies, but also on how experimental design, study sample issues, and definition of 'response' can significantly impact our interpretation of findings. Understanding the pharmacogenetics of anti-diabetes medications will provide critical baseline information for the development and implementation of genetic screening into therapeutic decision making, and lay the foundation for "individualized medicine" for patients with T2D.

  12. Newer antidiabetic drugs and calorie restriction mimicry.

    Science.gov (United States)

    Kalra, Sanjay; Jacob, Jubbin Jagan; Gupta, Yashdeep

    2016-01-01

    De-acceleration of aging and delayed development of age-related morbidity accompanies the restriction of calories (without malnutrition) in laboratory mice, nematodes, yeast, fish, and dogs. Recent results from long-term longitudinal studies conducted on primates have suggested longevity benefits of a 30% restriction of calories in rhesus monkeys as well. Among calorie restricted rhesus monkeys one of the mechanisms for the improvement in lifespan was the reduction in the development of glucose intolerance and cardiovascular disease. Although there are no comparable human studies, it is likely that metabolic and longevity benefits will accompany a reduction in calories in humans as well. However, considering the difficulties in getting healthy adults to limit food intake science has focused on understanding the biochemical processes that accompany calorie restriction (CR) to formulate drugs that would mimic the effects of CR without the need to actually restrict calories. Drugs in this emerging therapeutic field are called CR mimetics. Some of the currently used anti-diabetic agents may have some CR mimetic like effects. This review focuses on the CR mimetic properties of the currently available anti-diabetic agents.

  13. Cost effectiveness of insulin glargine plus oral antidiabetes drugs compared with premixed insulin alone in patients with type 2 diabetes mellitus in Canada.

    Science.gov (United States)

    Tunis, Sandra L; Sauriol, Luc; Minshall, Michael E

    2010-01-01

    Several treatment options are available for patients with type 2 diabetes mellitus who are making the transition from oral antidiabetes drugs (OADs) to insulin. Two options currently recommended by the Canadian Diabetes Association for initiating insulin therapy in patients with type 2 diabetes who are no longer responsive to OADs alone are insulin glargine plus OADs, and premixed insulin therapy only. Because of differences in efficacy, adverse events (such as hypoglycaemia) and acquisition costs, these two treatment options may lead to different long-term clinical and economic outcomes. To determine the cost effectiveness of insulin glargine plus OADs compared with premixed insulin without OADs in insulin-naive patients with type 2 diabetes in Canada. Using treatment effects taken from a published clinical trial, the validated IMS-CORE Diabetes Model was used to simulate the long-term cost effectiveness of insulin glargine with OADs, versus premixed insulin. Input treatment effects for the two therapeutic approaches were based on changes in glycosylated haemoglobin A(1c) (HbA(1c)) at clinical trial endpoint, and hypoglycaemia rates. The analysis was conducted from the perspective of the Canadian Provincial payer. Direct treatment and complication costs were obtained from published sources (primarily from Ontario) and reported in $Can, year 2008 values. All base-case costs and outcomes were discounted at 5% per year. Sensitivity analyses were conducted around key parameters and assumptions used in the study. Outcomes included direct medical costs associated with both treatment and diabetes-related complications. Cost-effectiveness outcomes included total average lifetime (35 years) costs, life expectancy (LE), QALYs and incremental cost-effectiveness ratios (ICERs). Base-case analyses showed that, compared with premixed insulin only, insulin glargine in combination with OADs was associated with a 0.051-year increase in LE and a 0.043 increase in QALYs. Insulin

  14. [The mortality of patients with diabetes mellitus using oral antidiabetic drugs in the Czech Republic decreased over the decade of 2003-2013 and came closer to the population average].

    Science.gov (United States)

    Brož, Jan; Honěk, Petr; Dušek, Ladislav; Pavlík, Tomáš; Kvapil, Milan

    2015-11-01

    Every year official data is published which describes the care of patients with diabetes mellitus in the Czech Republic. An overall number of individuals with diabetes, the number of newly reported cases and the number of patient deaths is always specified. However this data does not allow us to identify the differences in mortality between the individual cohorts of diabetic patients in relation to therapy. Comparison of the mortality development in the periods of 2002-2006 and 2010-2013 in a representative sample of the patient population with type 2 diabetes mellitus using oral antidiabetic drugs, kept in the database of the General Health Insurance Company of the Czech Republic (VZP) which provided health care coverage for 63% of Czech population in 2013. A retrospective epidemiologic analysis. We identified all individuals in the VZP database who had a record of DM diagnosis (E10-E16 based on ICD 10) or who had any antidiabetic therapy prescribed (ATC group A10) in the periods of 2002-2008 and 2009-2013. We only selected those patients for the analysis who were treated with oral antidiabetic medicines (in the given year or the preceding years they had a record of treatment with at least one medicine from A10B group, while having no record of treatment with medicines from A10A group within both years). 237,665 individuals met the selected criteria in 2003 and 315,418 individuals in 2013. Mortality rates dropped for all age groups (from 2003-2013): for 50-59 year olds by 1.2%-0.7%; in 60-69 year olds by 2.6%-1.6%; for 70-79 year olds by 5.8%-3.5%. In 2013 mortality rates came close to the general population where for the same age groups they reached 0.6%, 1.5% and 3.4% respectively. When expressed in relative terms, the mortality among 50-59 year olds declined by 42% (Czechia by 25%), among 60-69 year olds by 39% (Czechia by 17%) and among 70-79 year olds by 40% (Czechia by 28%) from the year 2003. The decline in mortality among the patients with DM treated with

  15. Recommendations on the effect of antidiabetic drugs in bone.

    Science.gov (United States)

    Rozas-Moreno, Pedro; Reyes-García, Rebeca; Jódar-Gimeno, Esteban; Varsavsky, Mariela; Luque-Fernández, Inés; Cortés-Berdonces, María; Muñoz-Torres, Manuel

    2017-03-01

    To provide recommendations on the effect of antidiabetic drugs on bone fragility to help select the most adequate antidiabetic treatment, especially in diabetic patients with high risk of fracture. Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. The GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) was used to establish both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each antidiabetic drug: AND "osteoporosis", "fractures", "bone mineral density", "bone markers", "calciotropic hormones". Papers in English with publication date before 30 April 2016 were reviewed. Recommendations were jointly discussed by the Working Group. The document summaries the data on the potential effects of antidiabetic drugs on bone metabolism and fracture risk. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. MICROEMULSIONS AS ANTIDIABETIC DRUG DELIVERY SYSTEMS

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    Omnia Sarhan, Mahmoud M. Ibrahim* and Mahmoud Mahdy

    2012-11-01

    Full Text Available Glibenclamide is practically insoluble in water and its gastrointestinal absorption is limited by its dissolution rate. Therefore, to enhance the drug dissolution and its hypoglycemic effects, the drug was formulated in different microemulsion systems and in vitro/in vivo evaluated. Microemulsion systems were prepared by Water titration method in which surfactants and cosurfactants (S/CoS were mixed at different weight ratios of 1:1, 2:1 and 3:1. They were subjected to transmission electron microscopical examination, pH determination and viscosity tests. The solubility of Glibenclamide in different microemulsion systems was determined. Forms 8, 9, 10, 11, 14 and 18 were found to have high Glibenclamide solubility using different oils. Form 11 and 9 showed the highest Glibenclamide release rates of 59.72% and 52.35%, respectively after 6 hours. In-vivo studies were tested using diabetic rats by application of form 11 with n-butanol as cosurfactant transdermally and form 8 with propylene glycol cosurfactant orally and transdermally. The results were compared to the drug suspension as a positive control. It was shown that microemulsion systems gave an effective tool of increasing drug dissolution probably due to enhanced wettability and reduced drug particle size, which in turn led to enhance its hypoglycemic effects.

  17. Adherence to treatment for diabetes mellitus: validation of instruments for oral antidiabetics and insulin

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    Lilian Cristiane Gomes-Villas Boas

    2014-01-01

    Full Text Available OBJECTIVES: to verify the face validity, criterion-related validity and the reliability of two distinct forms of presentation of the instrument Measurement of Adherence to Treatment, one being for ascertaining the adherence to the use of oral antidiabetics and the other for adherence to the use of insulin, as well as to assess differences in adherence between these two modes of drug therapy. METHOD: a methodological study undertaken with 90 adults with Type 2 Diabetes Mellitus. The criterion-related validity was verified using the Receiver Operating Characteristic curves; and for the reliability, the researchers calculated the Cronbach alpha coefficient, the item-total correlation, and the Pearson correlation coefficient. RESULTS: the oral antidiabetics and the other showed sensitivity of 0.84, specificity of 0.35 and a Cronbach correlation coefficient of 0.84. For the adherence to the use of insulin, the values found were, respectively, 0.60, 0.21 and 0.68. A statistically significant difference was found between the final scores of the two forms of the instrument, indicating greater adherence to the use of insulin than to oral antidiabetics. CONCLUSION: it is concluded that the two forms of the Measurement of Adherence to Treatment instrument are reliable and should be used to evaluate adherence to drug treatment among people with diabetes mellitus.

  18. Study of variation in price of various antidiabetic drugs available in Indian market

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    Amit Padmakar Date

    2015-02-01

    Conclusion: The average percentage price variation of different brands of the same oral antidiabetic drug manufactured in India is very wide. The appropriate changes in the government policy, sensitizing the prescribers about cost of therapy and proper management of marketing drugs should be directed toward maximizing the benefits of therapy and minimizing negative economic consequences. [Int J Basic Clin Pharmacol 2015; 4(1.000: 36-40

  19. Analytical tools for determination of new oral antidiabetic drugs, glitazones, gliptins, gliflozins and glinides, in bulk materials, pharmaceuticals and biological samples

    Directory of Open Access Journals (Sweden)

    Gumieniczek Anna

    2016-01-01

    Full Text Available The review presents analytical methods for determination of new oral drugs for the treatment of type 2 diabetes mellitus (T2DM, focusing on peroxisome proliferator-activated receptor gamma agonists (glitazones, dipeptidyl peptidase 4 inhibitors (gliptins and sodium/glucose co-transporter 2 inhibitors (gliflozins. Drugs derived from prandial glucose regulators, such as glinides, are considered because they are present in some new therapeutic options. The review presents analytical procedures suitable for determination of the drugs in bulk substances, such as pharmaceuticals and biological samples, including HPLC-UV, HPLC/LC-MS, TLC/HPTLC, CE/CE-MS, spectrophotometric (UV/VIS, spectrofluorimetric and electrochemical methods, taken from the literature over the past ten years (2006-2016. Some new procedures for extraction, separation and detection of the drugs, including solid phase extraction with molecularly imprinted polymers (SPE-MIP, liquid phase microextraction using porous hollow fibers (HP-LPME, HILIC chromatography, micellar mobile phases, ion mobility spectrometry (IMS and isotopically labeled internal standards, are discussed.

  20. The Recent Progress in Oral Anti-diabetic Drug Research and Development%口服抗糖尿病药物研发新进展

    Institute of Scientific and Technical Information of China (English)

    穆曼娜

    2011-01-01

    The study of oral anti - diabetic drug ( OAD ) is continuously progressing in recent years. Thiazolidinediones, glucagon-like peptide-1 receptor activator, dipeptidyl peptidase Ⅳ inhibitors and amylin analogs are already in the market; Glucokinase activator, vanadium complex compounds and bioactive chromium are in study. Besides,the formulations of the existing drugs are also in constant improvement. Gastrointestinal therapeutic system ( GITS ) tablets, sustained - release tablets and complex compounds are emerging gradually. These progresses provide more ways to treat diabetes for better effects.%口服抗糖尿病药物的研发不断取得成功,已经上市的有噻唑烷二酮类、胰高糖素样肽1受体激动剂、二肽基肽酶Ⅳ抑制剂和胰淀素类似物等,正在进行研究的有葡萄糖激酶激活剂、钒复合物和生物活性铬等.原有的药物也在剂型上不断改进,控释剂、缓释剂和复方型逐渐出现.这些研究的成功为糖尿病的治疗提供更多的手段,以期达到更好的治疗效果.

  1. A study on ethosomes as mode for transdermal delivery of an antidiabetic drug.

    Science.gov (United States)

    Bodade, Siddhodhan S; Shaikh, Karimunnisa Sameer; Kamble, Meghana S; Chaudhari, Praveen D

    2013-01-01

    A transdermal delivery system is warranted for repaglinide (RPG) which possesses half-life of 1 h and oral bioavailability of 56%. Ethosomes are useful tools for transdermal drug delivery. To prepare and evaluate ethosomes as mode for transdermal delivery of RPG. Ethosomes loaded with RPG were prepared from dipalmitoyl phosphatidylcholine and ethanol by the cold method. They were characterized using Fourier transform infrared spectroscopy and differential scanning calorimetry. They were evaluated for vesicle size, entrapment efficiency and ex-vivo skin permeation. Ethosomal composition was optimized using the 3(2) factorial design. Gel containing optimzsed ethosomes was studied for antidiabetic activity in rats. RPG ethosomes possessing the size of 0.171-1.727 µm and entrapment efficiency of 75-92% were obtained. They demonstrated a significantly higher permeation (64-97% of the administered dose) across excised rat skin when compared to free drug and its hydro alcoholic solution. In-vivo, RPG ethosomal system caused sustained antidiabetic effect. The lipid and ethanol concentration affected the physicochemical attributes and performance of ethosomes. The flexible ethosomes permeated the stratum corneum and improvized the availability of RPG for antidiabetic action. They prolonged the antidiabetic effect of RPG over a significantly longer period of time in comparison with the equivalent oral dose. Ethosomal system can successfully deliver RPG transdermally; sustain its effect and thus reduce its dosing frequency. Ethosomes are useful for enhancing the efficacy of RPG in the treatment of diabetes.

  2. Drug-drug Interaction between Pravastatin and Gemfibrozil (Antihyperlipidemic) with Gliclazide (Antidiabetic) in Rats.

    Science.gov (United States)

    Sultanpur, Cm; Satyanarayana, S; Reddy, Ns; Kumar, Ke; Kumar, S

    2010-04-01

    Diabetes mellitus is a condition of increased blood glucose level in the body. Antihyperlipidemic drugs like statins and fibrates are widely used for prophylactic treatment in dyslipideamia and atherosclerosis. Diabetic dislipidemia exists with increased triglycerides, low HDL and high LDL levels. Hence, with oral hypoglycemic drugs, the addition of a lipid-lowering drug is necessary for controlling dislipidemia. In such a situation, there may be chances of drug-drug interactions between antidiabetic and antihyperlipidemic drugs. The present study is planned to evaluate the safety of gliclazide (antidiabetic) in the presence of pravastatin and gemfibrozil (antihyperlpidemic) in rats. Studies in normal and alloxan-induced diabetic rats were conducted with oral doses of gliclazide and their combination with pravastatin and gemfibrozil, with an adequate washout period in between the treatments. Blood samples were collected in rats by retroorbital puncture at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h. All the blood samples were analyzed for glucose by GOD -POD. Gliclazide (½ TD) produced hypoglycemic activity in normal and diabetic rats, with peak activity at 2 and 8 h. Pravastatin (TD) + gemfibrozil (TD) combination treatment increased the hypoglycemic effect of gliclazide in normal rats or diabetic rats when administered together. The interaction observed due to inhibition of both the enzymes (CYP 450 2C9 and CYP 450 3A4) responsible for the metabolism of gliclazide showed increased half-life, which was seen in the present study. Because concomitant administration of gliclazide with provastatin and gemfibrozil in diabetes is associated with atherosclerosis, it should be contraindicated or used with caution.

  3. [Oral antidiabetics of the sulfonylurea group and their problems in therapy].

    Science.gov (United States)

    Füsgen, I; Summa, J D

    1980-01-01

    By the abolition of biguanids as oral antidiabetics the importance of derivatives of sulfonylcarbamids became prominent in the treatment of diabetic elderly patients. Because of the properties of that group, there are a number of problems by the therapy with these derivatives. There is the mostly existing multimorbidity in geriatric patients with the risk of incompatibilities of drugs in cause of multitherapy and there is the influence of morbid states on the pharmacokinetics. Some of the various questions will be shortly described in this article. There are then given also practical advices for the relations with the derivatives of sulfonylcarbamids in treating diabetic patients.

  4. Standardization of some herbal antidiabetic drugs in polyherbal formulation

    Directory of Open Access Journals (Sweden)

    Harinarayan Singh Chandel

    2011-01-01

    Full Text Available Background: Ayurvedic formulations are used to treat a wide variety of diseases including diabetes mellitus Standardization of herbal formulation is essential in order to assess the quality of drugs. The present paper reports standardization of eight herbal anti-diabetic drugs−Momordica charantia (seeds, Syzigium cumini (seeds, Trigonella foenum (seeds, Azadirachta indica (leaves, Emblica offi cinalis (fruits, Curcuma longa (rhizomes, Gymnema sylvestre (leaves, Pterocarpus marsupium (heart-wood individually and in polyherbal marketed samples of Baidyanath Madhumehari Churna Material and Methods: Shivayu Madhuhari Churna, Meghdut Madhushoonya Churna and were compared to the in-house preparation for physicochemical properties. Results and Conclusions: The limits obtained from the different physicochemical parameters of the individual eight herbal drugs and the marketed formulations could be used as reference standard for standardization of the anti-diabetic drugs in a quality control laboratory.

  5. Standardization of some herbal antidiabetic drugs in polyherbal formulation

    Science.gov (United States)

    Chandel, Harinarayan Singh; Pathak, A. K.; Tailang, Mukul

    2011-01-01

    Background: Ayurvedic formulations are used to treat a wide variety of diseases including diabetes mellitus Standardization of herbal formulation is essential in order to assess the quality of drugs. The present paper reports standardization of eight herbal anti-diabetic drugs–Momordica charantia (seeds), Syzigium cumini (seeds), Trigonella foenum (seeds), Azadirachta indica (leaves), Emblica offi cinalis (fruits), Curcuma longa (rhizomes), Gymnema sylvestre (leaves), Pterocarpus marsupium (heart-wood) individually and in polyherbal marketed samples of Baidyanath Madhumehari Churna Material and Methods: Shivayu Madhuhari Churna, Meghdut Madhushoonya Churna and were compared to the in-house preparation for physicochemical properties. Results and Conclusions: The limits obtained from the different physicochemical parameters of the individual eight herbal drugs and the marketed formulations could be used as reference standard for standardization of the anti-diabetic drugs in a quality control laboratory. PMID:21731396

  6. Should methods of correction for multiple comparisons be applied in pharmacovigilance? Reasoning around an investigation on safety of oral antidiabetic drugs

    OpenAIRE

    Scotti, Lorenza; Romio, Silvana; Ghirardi, Arianna; Arfe, Andrea; Casula, Manuela; Hazell, Lorna; Lapi, Francesco; Catapano, Alberico; Sturkenboom, Miriam; Corrao, Giovanni

    2015-01-01

    textabstractBACKGROUND: In pharmacovigilance, spontaneous reporting databases are devoted to the early detection of adverse event ‘signals’ of marketed drugs. A common limitation of these systems is the wide number of concurrently investigated associations, implying a high probability of generating positive signals simply by chance. However it is not clear if the application of methods aimed to adjust for the multiple testing problems are needed when at least some of the drug-outcome relation...

  7. Should methods of correction for multiple comparisons be applied in pharmacovigilance? Reasoning around an investigation on safety of oral antidiabetic drugs

    NARCIS (Netherlands)

    L. Scotti (Lorenza); S.A. Romio (Silvana); A. Ghirardi (Arianna); A. Arfe (Andrea); M. Casula (Manuela); L. Hazell (Lorna); F. Lapi (Francesco); A. Catapano (Alberico); M.C.J.M. Sturkenboom (Miriam); G. Corrao (Giovanni)

    2015-01-01

    textabstractBACKGROUND: In pharmacovigilance, spontaneous reporting databases are devoted to the early detection of adverse event ‘signals’ of marketed drugs. A common limitation of these systems is the wide number of concurrently investigated associations, implying a high probability of generating

  8. Pharmacogenetics of Anti-Diabetes Drugs

    OpenAIRE

    Johanna K. DiStefano; Watanabe, Richard M

    2010-01-01

    A variety of treatment modalities exist for individuals with type 2 diabetes mellitus (T2D). In addition to dietary and physical activity interventions, T2D is also treated pharmacologically with nine major classes of approved drugs. These medications include insulin and its analogues, sulfonylureas, biguanides, thiazolidinediones (TZDs), meglitinides, α-glucosidase inhibitors, amylin analogues, incretin hormone mimetics, and dipeptidyl peptidase 4 (DPP4) inhibitors. Pharmacological treatment...

  9. Association between patients' beliefs and oral antidiabetic medication adherence in a Chinese type 2 diabetic population

    OpenAIRE

    Wu P; Liu N

    2016-01-01

    Ping Wu,1 Naifeng Liu2 1Department of Clinical Pharmacy, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, 2Institute of Cardiovascular Disease, Southeast University Medical School, Nanjing, People’s Republic of China Purpose: The objective of this study was to identify, using the theory of planned behavior (TPB), patients’ beliefs about taking oral antidiabetic drugs (OADs) as prescribed, and to measure the correlations between bel...

  10. Pharmacoeconomics of the oral antidiabetic drugs in National Essential Medicine%国家基本药物中口服降糖药的药物经济学分析

    Institute of Scientific and Technical Information of China (English)

    江学容; 成小蔓

    2011-01-01

    比较国家基本药物中口服降糖药治疗2型糖尿病的经济效果.选取体重指数19~27 kg/m2的2型糖尿病患者200例,分为5组,每组40例,分别给予格列本脲(A组)、格列吡嗪(B组)、二甲双胍(C组)、格列本脲+二甲双胍(D组)、格列吡嗪+二甲双胍(E)进行治疗,观察疗效,采用药物经济学中的成本-效果分析法(CEA)进行分析.5组均可有效控制血糖,均可显著降低HbA1c.格列本脲更符合药物经济学原则,但由于易发生严重而持久的低血糖限制其临床广泛应用,老年患者应更加慎重;在以控制空腹血糖和体重为主要目标时选择二甲双胍更经济;在以控制餐后血糖为主要目标时选择格列吡嗪更为合理,尤其是体形偏瘦者更为合适;格列吡嗪+二甲双胍联合用药方案适合单用格列吡嗪或二甲双胍效果不佳者,值得推荐.%To compare the economic efficacies of the oral antidiabetic drugs in National Essential Medicine for treating type 2 diabetes mellitus.200 diabetic patients with body mass indices between 19-27 kg/m2 were assigned into 5 groups:group A received glibenclamide,group B glipizide,group C metformin,group D glibenclamide +metformin,and group E glipizide + metformin.Pharmacoeconomic evaluation was performed by cost-effectiveness analysis( CEA ).Fasting glucose level in patients treated with these 5 drugs all decreased significantly,as well as HbA1c.Glibenclamide was more in line with the principles of pharmacoeconomics,but should be used carefully for its serious and prolonged hypoglycemia,especially in elderly patients.According to the method of cost-effectiveness analysis,it was more economical to use metformin to control fasting glucose level while it is more reasonable to use glipizide to control the postprandial glucose whereas controlling of postprandial blood glucose is considered as a priority.Glipizide+mefformin combination may be recommended to the patients whose blood glucose level is

  11. Combining insulins with oral antidiabetic agents: effect on hyperglycemic control, markers of cardiovascular risk and disease

    Directory of Open Access Journals (Sweden)

    Kjeld Hermansen

    2008-06-01

    Full Text Available Kjeld Hermansen, Lene Sundahl Mortensen, Marie-Louise HermansenDepartment of Endocrinology and Metabolism C, Aarhus University Hospital, DK-8000 Aarhus, DenmarkAbstract: Patients with type 2 diabetes mellitus (T2DM have an increased risk of cardiovascular disease (CVD. Unfortunately, several potential barriers exist for CVD risk management in diabetes, including the need for significant lifestyle changes, potential problems with hypoglycemia, weight gain, injection tolerability, treatment complexity with current diabetes therapies and other, unmodifiable factors. Improving glycemic control may impact CVD risk. Treatment of T2DM usually starts with lifestyle changes such as diet and exercise. When these become insufficient, pharmacotherapy is required. Various oral antidiabetic drugs (OADs are available that reduce hyperglycemia. The first line of therapy is usually metformin, since it does not increase weight and seems to have a beneficial effect on CVD mortality and risk factors. As T2DM progresses, insulin treatment becomes necessary for the majority of patients. The last few years have seen the development of long-acting, rapid-acting, and premixed insulin analog formulations. The treat-to-target algorithms of recent studies combining OADs plus insulin analogs have demonstrated that patients can reach glycemic treatment targets with low risk of hypoglycemia, greater convenience, and – with some analogs – limited weight gain vs conventional insulins. These factors may possibly have a positive influence on CVD risk. Future studies will hopefully elucidate the benefits of this approach.Keywords: diabetes mellitus, type 2 diabetes, cardiovascular disease, hyperglycemia, insulin, oral antidiabetic drugs

  12. Insulin versus an oral antidiabetic agent as add-on therapy in type 2 diabetes after failure of an oral antidiabetic regimen: a meta-analysis

    OpenAIRE

    Gamble, JM; Simpson, Scot H.; Brown, Lauren C.; Johnson, Jeffrey A

    2008-01-01

    Background Although evidence-based guidelines for the treatment of type 2 diabetes mellitus provide clear recommendations for initial therapy, evidence on an optimal treatment strategy after secondary failure is unclear. Purpose To compare the efficacy of add-on therapy using basal insulin versus an additional oral antidiabetic agent in patients with type 2 diabetes and secondary failure. Data sources We searched the following electronic databases from inception until June 2007: MEDLINE; EMBA...

  13. Drug–drug Interaction between Pravastatin and Gemfibrozil (Antihyperlipidemic) with Gliclazide (Antidiabetic) in Rats

    Science.gov (United States)

    Sultanpur, CM; Satyanarayana, S; Reddy, NS; Kumar, KE; Kumar, S

    2010-01-01

    Diabetes mellitus is a condition of increased blood glucose level in the body. Antihyperlipidemic drugs like statins and fibrates are widely used for prophylactic treatment in dyslipideamia and atherosclerosis. Diabetic dislipidemia exists with increased triglycerides, low HDL and high LDL levels. Hence, with oral hypoglycemic drugs, the addition of a lipid-lowering drug is necessary for controlling dislipidemia. In such a situation, there may be chances of drug–drug interactions between antidiabetic and antihyperlipidemic drugs. The present study is planned to evaluate the safety of gliclazide (antidiabetic) in the presence of pravastatin and gemfibrozil (antihyperlpidemic) in rats. Studies in normal and alloxan-induced diabetic rats were conducted with oral doses of gliclazide and their combination with pravastatin and gemfibrozil, with an adequate washout period in between the treatments. Blood samples were collected in rats by retroorbital puncture at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h. All the blood samples were analyzed for glucose by GOD –POD. Gliclazide (½ TD) produced hypoglycemic activity in normal and diabetic rats, with peak activity at 2 and 8 h. Pravastatin (TD) + gemfibrozil (TD) combination treatment increased the hypoglycemic effect of gliclazide in normal rats or diabetic rats when administered together. The interaction observed due to inhibition of both the enzymes (CYP 450 2C9 and CYP 450 3A4) responsible for the metabolism of gliclazide showed increased half-life, which was seen in the present study. Because concomitant administration of gliclazide with provastatin and gemfibrozil in diabetes is associated with atherosclerosis, it should be contraindicated or used with caution. PMID:21264118

  14. Optimizing weight control in diabetes: antidiabetic drug selection

    Directory of Open Access Journals (Sweden)

    S Kalra

    2010-08-01

    Full Text Available S Kalra1, B Kalra1, AG Unnikrishnan2, N Agrawal3, S Kumar41Bharti Hospital, Karnal; 2Amrita Institute of Medical Science, Kochi; 3Medical College, Gwalior; 4Excel Life Sciences, Noida, IndiaDate of preparation: 18th August 2010Conflict of interest: SK has received speaker fees from Novo Nordisk, sanofi-aventis, MSD, Eli Lilly, BMS, and AstraZeneca.Clinical question: Which antidiabetic drugs provide optimal weight control in patients with type 2 diabetes?Results: Metformin reduces weight gain, and may cause weight loss, when given alone or in combination with other drugs. Pioglitazone and rosiglitazone use is associated with weight gain. Use of the glucagon-like peptide-1 (GLP-1 analogs, liraglutide and exenatide, is associated with weight loss. Dipeptidyl peptidase-4 (DPP-4 inhibitors are considered weight-neutral. Results with insulin therapy are conflicting. Insulin detemir provides weight control along with glycemic control.Implementation: • Weight gain is considered an inevitable part of good glycemic control using conventional modalities of treatment such as sulfonylureas.• Use of metformin, weight-sparing insulin analogs such as insulin detemir, and liraglutide, should be encouraged as monotherapy, or in combination with other drugs.Keywords: weight control, diabetes

  15. Selective speciation improves efficacy and lowers toxicity of platinum anticancer and vanadium antidiabetic drugs.

    Science.gov (United States)

    Doucette, Kaitlin A; Hassell, Kelly N; Crans, Debbie C

    2016-12-01

    Improving efficacy and lowering resistance to metal-based drugs can be addressed by consideration of the coordination complex speciation and key reactions important to vanadium antidiabetic drugs or platinum anticancer drugs under biological conditions. The methods of analyses vary depending on the specific metal ion chemistry. The vanadium compounds interconvert readily, whereas the reactions of the platinum compounds are much slower and thus much easier to study. However, the vanadium species are readily differentiated due to vanadium complexes differing in color. For both vanadium and platinum systems, understanding the processes as the compounds, Lipoplatin and Satraplatin, enter cells is needed to better combat the disease; there are many cellular metabolites, which may affect processing and thus the efficacy of the drugs. Examples of two formulations of platinum compounds illustrate how changing the chemistry of the platinum will result in less toxic and better tolerated drugs. The consequence of the much lower toxicity of the drug, can be readily realized because cisplatin administration requires hospital stay whereas Lipoplatin can be done in an outpatient manner. Similarly, the properties of Satraplatin allow for development of an oral drug. These forms of platinum demonstrate that the direct consequence of more selective speciation is lower side effects and cheaper administration of the anticancer agent. Therefore we urge that as the community goes forward in development of new drugs, control of speciation chemistry will be considered as one of the key strategies in the future development of anticancer drugs.

  16. Immunomodulatory effects of oral antidiabetic drugs in lymphocyte cultures from patients with type 2 diabetes Efeito imunomodulador de hipoglicemiantes orais em cultura de linfócitos de pacientes com diabetes tipo 2

    OpenAIRE

    2011-01-01

    INTRODUCTION AND OBJECTIVE: It has been suggested that type 2 diabetes is an inflammatory response manifestation. The main drugs used to treat type 2 diabetes are sulphonylureas and biguanides. The aim of this study was to demonstrate the modulatory effects of oral hypoglycemic drugs (chlorpropamide and metformin) on lymphocyte proliferation in vitro and ex vivo. METHODS: Peripheral blood mononuclear cells were isolated from human blood by gradient centrifugation. T-lymphocytes were stimulate...

  17. 胰岛素类似物联合口服降糖药治疗2型糖尿病%Insulin analogs combined with oral antidiabetic drugs in treating patients with type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    周泽华; 肖蓉; 何煦; 瞿文娟; 杨刚毅; 李伶; 李志勇

    2013-01-01

    目的:评估3种胰岛素类似物(地特胰岛素、甘精胰岛素、双相门冬胰岛素30)联合口服降糖药用于治疗血糖控制欠佳的2型糖尿病患者的有效性及安全性.方法:73例血糖控制不达标的2型糖尿病患者被分为3组:每日睡前1次地特胰岛素组(n=23),每日睡前1次甘精胰岛素组(n=27)和每日早晚餐前各1次双相门冬胰岛素30组(n=23),各组均联合使用口服降糖药,共治疗16周.分析比较3组患者治疗前后糖化血红蛋白(hemoglobin A1c,HbA1c)、空腹血糖(fasting blood glucose,FBG)、餐后血糖(postprandial blood glucose,PBG)、体质指数(body mass index,BMI)的变化.评估3组间HbA1c、FBG、PBG下降幅度、HbA1c达标率(<7%)和低血糖事件的发生率.结果:治疗前3组HbA1c、FBG、PBG均无显著差异.经16周治疗,3组HbA1c、FBG、PBG均较治疗前显著下降(P<0.01),但组间比较无显著差异(P>0.05).各组治疗前后BMI均无显著变化(P>0.05).地特胰岛素组、甘精胰岛素组、双相门冬胰岛素30组HbA1c达标率(<7%)分别为43%、59%、52%,组间比较无显著差异(P>0.05).地特胰岛素组、甘精胰岛素组、双相门冬胰岛素30组分别发生3例(13%)、2例(7%)、5例(22%)轻度低血糖,均无严重低血糖事件发生,各组间低血糖发生率无显著差异(P>0.05).结论:在本研究人群中,有效控制FBG是HbA1c降低及达标的有效手段,3种胰岛素类似物联合口服降糖治疗2型糖尿病,可达到同样的降糖效果,并且体质量无明显增加、低血糖发生率较低.%Objective:To evaluate the efficacy and safety of insulin analogs (Insulin detemir,Insulin glargine,B iphasic insulin aspart 30) combined with oral antidiabetic drugs(OADs) in treating type 2 diabetic mellitus patients whose blood glucose is insufficiently controlled.Methods:Seventy-three type 2 diabetic mellitus patients with insufficiently controlled blood glucose were assigned to three groups

  18. Polypharmacy in elderly patients with type 2 diabetes receiving oral antidiabetic treatment.

    Science.gov (United States)

    Noale, Marianna; Veronese, Nicola; Cavallo Perin, Paolo; Pilotto, Alberto; Tiengo, Antonio; Crepaldi, Gaetano; Maggi, Stefania

    2016-04-01

    Polypharmacy in older diabetics can have detrimental effects linked to poor adherence and the risk of drug interaction or more serious/frequent side effects. The aim of this study was to identify the characteristics associated with polypharmacy in a cohort of elderly diabetic patients being treated with oral hypoglycemic agents. The study population consisted of 1342 diabetic patients consecutively enrolled in 57 diabetes centers in Italy participating in the METABOLIC Study. Patients meeting the following inclusion criteria were enrolled: diagnosis of type 2 diabetes mellitus, age ≥65 years, and receiving oral antidiabetic treatment. Data concerning diabetes duration and complications, the medications the patients were taking, and the number of hypoglycemic events were registered. Multidimensional impairment was assessed using the Multidimensional Prognostic Index. The mean age of the participants was 73.3 ± 5.5 years. Polypharmacy, defined as being prescribed contemporaneously at least five drugs, was found in 57.1 % of the study population. According to a multivariable logistic model, the female gender was significantly associated with polypharmacy, as were living in Northern Italian regions, diabetes duration longer than 4 years, and having a body mass index ≥30 kg/m(2). Comorbidities, diabetes complications, a better cognitive performance on the Short Portable Mental Status Questionnaire, and being malnourished/at risk of malnourishment according to the mini nutritional assessment were associated with polypharmacy. Polypharmacy, a condition that may lead to many potential detrimental outcomes in older diabetic subjects, was significantly associated with some risk factors that may be useful to identify subjects at risk.

  19. Immunomodulatory effects of oral antidiabetic drugs in lymphocyte cultures from patients with type 2 diabetes Efeito imunomodulador de hipoglicemiantes orais em cultura de linfócitos de pacientes com diabetes tipo 2

    Directory of Open Access Journals (Sweden)

    Karina Faccio Mello

    2011-02-01

    Full Text Available INTRODUCTION AND OBJECTIVE: It has been suggested that type 2 diabetes is an inflammatory response manifestation. The main drugs used to treat type 2 diabetes are sulphonylureas and biguanides. The aim of this study was to demonstrate the modulatory effects of oral hypoglycemic drugs (chlorpropamide and metformin on lymphocyte proliferation in vitro and ex vivo. METHODS: Peripheral blood mononuclear cells were isolated from human blood by gradient centrifugation. T-lymphocytes were stimulated by phytohemagglutinin (PHA and oral hypoglycemic drugs. RESULTS: In both in vitro and ex vivo experiments, there was a reduction in cell proliferation after treatment with oral hypoglycemic drugs. When both drugs were used in combination, a high level of cytotoxicity was observed, which made analysis of immunomodulatory effects unfeasible. DISCUSSION AND CONCLUSION: We demonstrated that diabetes itself may reduce cell proliferation significantly when stimulated by PHA, which may indicate that diabetic patients have difficulties in promoting an efficient inflammatory response. Moreover, the use of oral hypoglycemic drugs may aggravate this situation.INTRODUÇÃO E OBJETIVOS: Tem sido sugerido que o diabetes mellitus tipo 2 (DM2 é uma manifestação da resposta inflamatória. As principais drogas utilizadas no tratamento do DM2 são as sulfonilureias e as biguanidas. O objetivo deste trabalho é demonstrar os efeitos moduladores na proliferação de linfócitos causada pelos hipoglicemiantes orais (clorpropamida e metformina, in vitro e ex vivo. MÉTODOS: Células mononucleares de sangue periférico foram isoladas de seres humanos por gradiente de centrifugação. Os linfócitos T foram estimulados com fito-hemaglutinina (PHA e hipoglicemiantes. RESULTADOS: Nos experimentos in vitro e ex vivo, mostramos a redução da proliferação celular quando do tratamento com drogas hipoglicemiantes orais. Quando as drogas foram utilizadas em combinação, foi

  20. Beliefs related to adherence to oral antidiabetic treatment according to the Theory of Planned Behavior

    Directory of Open Access Journals (Sweden)

    Fernanda Freire Jannuzzi

    2014-08-01

    Full Text Available OBJECTIVE: to identify salient behavioral, normative, control and self-efficacy beliefs related to the behavior of adherence to oral antidiabetic agents, using the Theory of Planned Behavior.METHOD: cross-sectional, exploratory study with 17 diabetic patients in chronic use of oral antidiabetic medication and in outpatient follow-up. Individual interviews were recorded, transcribed and content-analyzed using pre-established categories.RESULTS: behavioral beliefs concerning advantages and disadvantages of adhering to medication emerged, such as the possibility of avoiding complications from diabetes, preventing or delaying the use of insulin, and a perception of side effects. The children of patients and physicians are seen as important social references who influence medication adherence. The factors that facilitate adherence include access to free-of-cost medication and taking medications associated with temporal markers. On the other hand, a complex therapeutic regimen was considered a factor that hinders adherence. Understanding how to use medication and forgetfulness impact the perception of patients regarding their ability to adhere to oral antidiabetic agents.CONCLUSION: medication adherence is a complex behavior permeated by behavioral, normative, control and self-efficacy beliefs that should be taken into account when assessing determinants of behavior.

  1. A stewardship intervention program for safe medication management and use of antidiabetic drugs

    Directory of Open Access Journals (Sweden)

    Zhao RY

    2015-07-01

    Full Text Available Rui-yi Zhao,1 Xiao-wen He,1 Yan-min Shan,1 Ling-ling Zhu,2 Quan Zhou3 1Clinical Nurse Specialist Section, Division of Nursing, 2Geriatric VIP Care Ward, Division of Nursing, 3Department of Pharmacy, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China Background: Diabetes patients are complex due to considerations of polypharmacy, multimorbidities, medication adherence, dietary habits, health literacy, socioeconomic status, and cultural factors. Meanwhile, insulin and oral hypoglycemic agents are high-alert medications. Therefore it is necessary to require a multidisciplinary team’s integrated endeavors to enhance safe medication management and use of antidiabetic drugs.Methods: A 5-year stewardship intervention program, including organizational measures and quality improvement activities in storage, prescription, dispensing, administration, and monitoring, was performed in the Second Affiliated Hospital of Zhejiang University, People’s Republic of China, a 3,200-bed hospital with 3.5 million outpatient visits annually.Results: The Second Affiliated Hospital of Zhejiang University has obtained a 100% implementation rate of standard storage of antidiabetic drugs in the Pharmacy and wards since August 2012. A zero occurrence of dispensing errors related to highly “look-alike” and “sound-alike” NovoMix 30® (biphasic insulin aspart and NovoRapid® (insulin aspart has been achieved since October 2011. Insulin injection accuracy among ward nurses significantly increased from 82% (first quarter 2011 to 96% (fourth quarter 2011 (P<0.05. The number of medication administration errors related to insulin continuously decreased from 20 (2011 to six (2014. The occurrence rate of hypoglycemia in non–endocrinology ward diabetes inpatients during 2011–2013 was significantly less than that in 2010 (5.03%–5.53% versus 8.27% (P<0.01. Percentage of correct management of

  2. Progress in drug gene polymorphism and varieties oral antidiabetic drug%药物基因多态性与口服降糖药物效应多样性关系的研究进展

    Institute of Scientific and Technical Information of China (English)

    王丹蕾; 于伟; 肖江宁

    2013-01-01

    2型糖尿病是一种高发的基础疾病,以药物治疗为主,饮食、运动为辅.在降糖药物的治疗中,由于个体差异,导致疗效及不良反应多样性.药物基因组学是导致这一差异的重要原因,其研究目的 是明确遗传因素对药物效应的影响,是近年来一大研究热点.并为临床合理用药提供理论依据,这也势必将成为未来医药学的一个重要发展方向.%Type 2 diabetes mellitus is a common epidemic disease, which depends on drug treatment adjuvant with diet and exercise. During the drug treatment, varieties of curative effect and adverse effect resulted of individual difference. While pharmacogenomics is an important cause of individual difference and one of hot points of investigation. Pharmacogenomics will be an important direction of medical and pharmaceutical development as a theoretical foundation for rational use of drug and personalized treatment.

  3. Prospective, non-interventional, uncontrolled, open-chart, pharmacoepidemiologic study of prescribing patterns for anti-diabetic drugs at tertiary care hospital in Erode

    Directory of Open Access Journals (Sweden)

    Radhika P

    2009-01-01

    Full Text Available The aim of this study is to determine current prescribing patterns for anti-diabetic drugs adopted by physicians in Erode. The prospective, non interventional, uncontrolled, open-chart, pharmacoepidemiological study was conducted from January -2007 to April -2007 at a diabetic care centre having 350 diabetic patients. The pattern of prescribing anti-diabetic drugs was recorded along with glycosylated haemoglobin levels, total cholesterol, high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein and triglycerides in insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus patients and the values were observed. The prescribing pattern of the oral anti-diabetic drugs shows that out of the various oral anti-diabetic drugs′ available, drugs from only two groups were prescribed. Sulphonylureas, biguanides and combination therapy accounts for 31.43%, 20.28% and 33.71% of prescriptions, respectively, while insulin alone and with OAD′s accounts for 6.28% and 8.29% prescriptions, respectively. Overall, prescribing trend is away from monotherapy with insulin and sulphonylureas and towards combination therapies.

  4. Pattern of anti-diabetic drugs prescribed in a tertiary care hospital of Bangladesh

    Directory of Open Access Journals (Sweden)

    Zuhayer Ahmed

    2016-02-01

    Conclusions: The findings can serve as a guide to choose the formulation and combination of anti-diabetic drugs in this part of the world before developing and marketing any new drug. [Int J Basic Clin Pharmacol 2016; 5(1.000: 6-12

  5. Patients’ beliefs about adherence to oral antidiabetic treatment: a qualitative study

    Directory of Open Access Journals (Sweden)

    Guénette L

    2015-03-01

    Full Text Available Line Guénette,1–3 Sophie Lauzier,1–3 Laurence Guillaumie,2–4 Gabriel Giguère,1 Jean-Pierre Grégoire,1–3 Jocelyne Moisan1–3 1Faculty of Pharmacy, Laval University, Quebec City, QC, Canada; 2Chair on Adherence to Treatments, Laval University, Quebec City, QC, Canada; 3CHU de Québec Research Center, Population Health and Optimal Practices Research Unit, Quebec City, QC, Canada; 4Faculty of Nursing, Laval University, Quebec City, QC, Canada Purpose: The purpose of this study was to elicit patients’ beliefs about taking their oral antidiabetic drugs (OADs as prescribed to inform the development of sound adherence-enhancing interventions.Methods: A qualitative study was performed. Adults with type 2 diabetes who had been taking an OAD for >3 months were solicited to participate in one of six focus groups. Discussions were facilitated using a structured guide designed to gather beliefs related to important constructs of the theory of planned behavior. Four coders using this theory as the theoretical framework analyzed the videotaped discussions.Results: Forty-five adults participated. The most frequently mentioned advantages for OAD-taking as prescribed were to avoid long-term complications and to control glycemia. Family members were perceived as positively influential. Carrying the OAD at all times, having the OAD in sight, and having a routine were important facilitating factors. Being away from home, not accepting the disease, and not having confidence in the physician’s prescription were major barriers to OAD-taking.Conclusion: This study elicited several beliefs regarding OAD-taking behavior. Awareness of these beliefs may help clinicians adjust their interventions in view of their patients’ beliefs. Moreover, this knowledge is crucial to the planning, development, and evaluation of interventions that aim to improve medication adherence. Keywords: type 2 diabetes, medication adherence, theory of planned behavior, focus groups

  6. [Dapagliflozin, a novel oral antidiabetic with an uncertain future].

    Science.gov (United States)

    Escudero Vilaplana, Belén; Almodóvar Carretón, María José; Herrero Hernández, Silvia

    2014-11-03

    Objetivo: La diabetes mellitus tipo 2 (DM2) es uno de los principales problemas sociosanitarios a nivel mundial, para la que existen multitud de tratamientos. Recientemente, se ha aprobado el primer farmaco de una nueva familia de antidiabeticos orales (ADO): la dapagliflozina. Nuestro objetivo es revisar la evidencia cientifica disponible sobre la dapagliflozina, con el fin de analizar su eficacia, seguridad y coste y poder estimar su papel en la farmacoterapia actual de la DM2. Métodos: La eficacia y seguridad de la dapagliflozina se analizaron mediante una evaluacion de la evidencia cientifica. El coste de los diferentes ADO se calculo en base a sus dosis diarias definidas (DDD) y al precio de venta del laboratorio. Resultados: Se identificaron 7 ensayos clinicos aleatorizados: 2 en monoterapia (840 pacientes) y 5 en terapia combinada con otros antidiabeticos (3184 pacientes). En los 7 ensayos, la dapagliflozina redujo la concentracion de HbA1c; en todos se comparo con placebo, salvo en un estudio en terapia combinada que se comparo frente a farmaco activo (glipizida). Entre los efectos adversos mas frecuentes se detectaron infecciones genitourinarias e hipotension, aunque se debe prestar especial atencion al incremento del cancer de vejiga. Junto con los inhibidores de la DPP-4, la dapagliflozina es uno de los ADO de mayor coste (coste anual de DDD=729,3 euros). Conclusiones: La dapagliflozina no aporta ventajas respecto a la farmacoterapia de la DM2 ya existente. Su falta de experiencia de uso, la ausencia de importantes beneficios clinicos y su elevado coste hacen necesario restringir su utilizacion.

  7. HYPOGLYCEMIA INDUCED BY ANTIDIABETIC SULFONYLUREAS.

    Science.gov (United States)

    Confederat, Luminiţa; Constantin, Sandra; Lupaşcu, Florentina; Pânzariu, Andreea; Hăncianu, Monica; Profire, Lenuţa

    2015-01-01

    Diabetes mellitus is a major health problem due to its increasing prevalence and life-threatening complications. Antidiabetic sulfonylureas represent the first-line drugs in type 2 diabetes even though the most common associated risk is pharmacologically-induced hypoglycemia. In the development of this side effect are involved several factors including the pharmacokinetic and pharmacodynamic profile of the drug, patient age and behavior, hepatic or renal dysfunctions, or other drugs associated with a high risk of interactions. If all these are controlled, the risk-benefit balance can be equal to other oral antidiabetic drugs.

  8. Parametric time-to-onset models were developed to improve causality assessment of adverse drug reactions from antidiabetic drugs

    NARCIS (Netherlands)

    Scholl, Joep H G; van de Ven, Peter M; van Puijenbroek, Eugène P

    2015-01-01

    OBJECTIVES: The aim of this study was to investigate whether the time to onset (TTO) of common adverse drug reactions (ADRs) of antidiabetic drugs could be modeled using parametric distributions and whether these TTO distributions were dependent on patient characteristics. Furthermore, information r

  9. Pathways Targeted by Antidiabetes Drugs Are Enriched for Multiple Genes Associated With Type 2 Diabetes Risk

    NARCIS (Netherlands)

    Segre, Ayellet V.; Wei, Nancy; Altshuler, David; Florez, Jose C.; Wijmenga, T. N.; Ostaptchouk, J. V.

    2015-01-01

    Genome-wide association studies (GWAS) have uncovered >65 common variants associated with type 2 diabetes (T2D); however, their relevance for drug development is not yet clear. Of note, the first two T2D-associated loci (PPARG and KCNJ11/ABCC8) encode known targets of antidiabetes medications. We th

  10. A survey of prescription pattern of anti-diabetic drugs on diabetic patients with cardiovascular complications within Dhaka metropolis

    Directory of Open Access Journals (Sweden)

    Rubaba Karim

    2016-12-01

    Conclusions: The findings can serve as a guide to choose the formulation and combination of anti-diabetic drugs in this part of the world before developing and marketing any new drug. Therefore it is necessary to create better awareness among people, focus on rational use of anti-diabetic drugs and also motivate our physicians to prescribe the generic drugs. [Int J Basic Clin Pharmacol 2016; 5(6.000: 2397-2402

  11. Association between patients' beliefs and oral antidiabetic medication adherence in a Chinese type 2 diabetic population

    Directory of Open Access Journals (Sweden)

    Wu P

    2016-06-01

    Full Text Available Ping Wu,1 Naifeng Liu2 1Department of Clinical Pharmacy, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, 2Institute of Cardiovascular Disease, Southeast University Medical School, Nanjing, People’s Republic of China Purpose: The objective of this study was to identify, using the theory of planned behavior (TPB, patients’ beliefs about taking oral antidiabetic drugs (OADs as prescribed, and to measure the correlations between beliefs and medication adherence.Patients and methods: We performed a cross-sectional study of type 2 diabetic patients using structured questionnaires in a Chinese tertiary hospital. A total of 130 patients were enrolled to be interviewed about TPB variables (behavioral, normative, and control beliefs relevant to medication adherence. Medication adherence was assessed using the eight-item Morisky Medication Adherence Scale (MMAS-8. Spearman’s rank correlation was used to assess the association between TPB and MMAS-8. Logistic regression analysis was performed to examine the relationship between different variables and MMAS-8, with statistical significance determined at P<0.05.Results: From 130 eligible Chinese patients with an average age of 60.6 years and a male proportion of 50.8%, a nonsignificant relationship between behavioral, normative, and the most facilitating control beliefs and OAD adherence was found in our study. Having the OADs on hand (P=0.037 was the only facilitating control belief associated with adherence behavior. Being away from home or eating out (P=0.000, not accepting the disease (P=0.000, ignorance of life-long drug adherence (P=0.038, being busy (P=0.001, or poor memory (P=0.008 were control belief barriers found to be correlated with poor adherence. TPB is the only important determinant influencing OAD adherence among all the factors (P=0.011.Conclusion: The results indicate that the TPB model could be used to examine adherence to OADs. One

  12. SGLT-2 inhibitors: the glucosuric antidiabetics

    OpenAIRE

    Rekha Thaddanee; Ajeet Kumar Khilnani; Gurudas Khilnani

    2013-01-01

    Despite availability of a number of oral antidiabetics, a sizeable population of diabetics remains uncontrolled. Thus there is growing need of new group of drugs for diabetic control. Understanding renal conservation of glucose by efficient reabsorption through sodium glucose cotransporter-2 (SGLT-2) has paved way for development of an entirely new group of drugs, the SGLT-2 inhibitors. These glucosuric antidiabetic agents have shown promise in early clinical studies. Canagliflozin is recentl...

  13. Antidiabetic Drugs: Mechanisms of Action and Potential Outcomes on Cellular Metabolism.

    Science.gov (United States)

    Meneses, Maria J; Silva, Branca M; Sousa, Mário; Sá, Rosália; Oliveira, Pedro F; Alves, Marco G

    2015-01-01

    Diabetes mellitus (DM) is one of the most prevalent chronic diseases and has been a leading cause of death in the last decades. Thus, methods to detect, prevent or delay this disease and its co-morbidities have long been a matter of discussion. Nowadays, DM patients, particularly those suffering with type 2 DM, are advised to alter their diet and physical exercise regimens and then proceed progressively from monotherapy, dual therapy, and multi-agent therapy to insulin administration, as the disease becomes more severe. Although progresses have been made, the pursuit for the "perfect" antidiabetic drug still continues. The complexity of DM and its impact on whole body homeodynamics are two of the main reasons why there is not yet such a drug. Moreover, the molecular mechanisms by which DM can be controlled are still under an intense debate. As the associated risks, disadvantages, side effects and mechanisms of action vary from drug to drug, the choice of the most suitable therapy needs to be thoroughly investigated. Herein we propose to discuss the different classes of antidiabetic drugs available, their applications and mechanisms of action, particularly those of the newer and/or most widely prescribed classes. A special emphasis will be made on their effects on cellular metabolism, since these drugs affect those pathways in several cellular systems and organs, promoting metabolic alterations responsible for either deleterious or beneficial effects. This is a crucial property that needs to be carefully investigated when prescribing an antidiabetic.

  14. Drug-drug interactions between immunosuppressants and antidiabetic drugs in the treatment of post-transplant diabetes mellitus.

    Science.gov (United States)

    Vanhove, Thomas; Remijsen, Quinten; Kuypers, Dirk; Gillard, Pieter

    2016-09-14

    Post-transplant diabetes mellitus is a frequent complication of solid organ transplantation that generally requires treatment with lifestyle interventions and antidiabetic medication. A number of demonstrated and potential pharmacokinetic drug-drug interactions (DDIs) exist between commonly used immunosuppressants and antidiabetic drugs, which are comprehensively summarized in this review. Cyclosporine (CsA) itself inhibits the cytochrome P450 (CYP) 3A4 enzyme and a variety of drug transporters. As a result, it increases exposure to repaglinide and sitagliptin, will likely increase the exposure to nateglinide, glyburide, saxagliptin, vildagliptin and alogliptin, and could theoretically increase the exposure to gliquidone and several sodium-glucose transporter (SGLT)-2 inhibitors. Currently available data, although limited, suggest that these increases are modest and, particularly with regard to gliptins and SGLT-2 inhibitors, unlikely to result in hypoglycemia. The interaction with repaglinide is more pronounced but does not preclude concomitant use if repaglinide dose is gradually titrated. Mycophenolate mofetil and azathioprine do not engage in DDIs with any antidiabetic drug. Although calcineurin inhibitors (CNIs) and mammalian target of rapamycin inhibitors (mTORi) are intrinsically prone to DDIs, their disposition is not influenced by metformin, pioglitazone, sulfonylureas (except possibly glyburide) or insulin. An effect of gliptins on the disposition of CNIs and mTORi is unlikely, but has not been definitively ruled out. Based on their disposition profiles, glyburide and canagliflozin could affect CNI and mTORi disposition although this requires further study. Finally, delayed gastric emptying as a result of glucagon-like peptide-1 agonists seems to have a limited, but not necessarily negligible effect on CNI disposition.

  15. Effect of Exenatide on Plasma Glucose,Weight and Body Fat in Poorly Controlled Type 2 Diabetes Patients Using Oral Antidiabetic Drug%艾塞那肽对2型糖尿病患者疗效、体重及体质成分的影响

    Institute of Scientific and Technical Information of China (English)

    卢林娜; 高政南; 朱珠; 罗兰; 刘羽晗; 王冰; 李欣宇; 牛敏; 侯桂梅

    2014-01-01

    Objective:To evaluate the effect of exenatide on plasma glucose,weight and body fat in poorly controlled type 2 diabetes patients using oral antidiabetic drug.Method:15 cases of poorly controlled type 2 diabetes who used oral antidiabetic drug in our hospital were selected. Exenatide was injected subcutaneously together with the original basis of oral hypoglycemic agents for three months,and the body weight,body mass index(BMI),the percentage of body fat tissue, the percentage of fat tissue of waist to hip and visceral fat range were analyzed by body composition analyzer before and after treatment. In the mean time,Dual-energy X-ray absorptiometry was used to determine the fat mass and percentage,muscle and bone mineral salts mass of upper limb,Lower limb,trunk,and whole body. Result:After 3 months’treatment,HbA1c were significantly decreased than before,had statistical differences(t=3.472,P0.05). The body weight,BMI, the percentage of body fat and visceral fat range were significantly decreased before and after treatment(t=4.424,P0.05). After 3 months’ treatment,the fat tissue mass of lower limb,trunk,and whole body were significantly decreased than before,had statistical differences(t=4.008,P0.05). The muscle and bone mineral salts mass were not altered(P>0.05). After 3 months’ treatment,the decrease of body weight was highly correlated with the decrease of trunk fat and whole body fat(r=0.860,0.819,P0.05);治疗后体重、体重指数、体脂百分比及内脏脂肪区域均明显下降,与治疗前比较差异均有统计学意义(t体重=4.424,P0.05);治疗后下肢、躯干、全身脂肪量较治疗前均明显下降,差异有统计学意义(t下肢脂肪量=4.008,P0.05);治疗前后上肢、下肢、躯干、全身肌肉及骨矿物盐含量无明显改变;治疗后体重下降幅度与躯干和全身脂肪量下降幅度高度相关(r=0.860、0.819,P<0.01);治疗后全身脂肪量下降幅度与下肢和躯干脂

  16. COST ANALYSIS OF ANTIDIABETIC DRUGS FOR DIABETES MELLITUS OUTPATIENT IN KODYA YOGYAKARTA HOSPITAL

    OpenAIRE

    TRI MURTI ANDAYANI; IKE IMANINGSIH

    2007-01-01

    Diabetes mellitus is a chronic disorder that has been recognised by the Indonesian government as a major public health problem with far reaching consequences not just for its adverse impact on the healthof Indonesians, but also for the economic burden it places on the healthcare systems. The objectives of this study were to describe the healthcare cost for outpatient diabetes mellitus treatment and to examine the cost of different classes of antidiabetic drug. The medical records of Type 2 di...

  17. Effects of antidiabetes drugs on functional independence measure on a subacute rehabilitation ward for stroke patients.

    Science.gov (United States)

    Kose, E; Toyoshima, M; Tachi, T; Teramachi, H; Kawakubo, T; Hayashi, H

    2015-07-01

    It has been reported that the improvement of activities of daily living (ADL) by rehabilitation affects glycemic control. However, there are no reports about antidiabetes drugs as factors affecting the outcomes of rehabilitation. Therefore, we investigated the effects of antidiabetes drugs on functional independence measure (FIM) [total (T), motor (M), and cognition (C) items] in stroke patients with diabetes who were discharged from the subacute rehabilitation ward. We chose the frequently used antidiabetes drugs [sulfonylurea (SU), dipeptidyl peptidase-IV inhibitors (DPP-IVIs), and α-glycosidase inhibitors (α-GIs)] as the basis for categorizing the patients. We compared the patients' background features and laboratory data among the three groups. As a result, when SU was used in stroke patients with diabetes, it is difficult to obtain significant FIM-M gain, FIM-C gain, FIM-M efficiency, and FIM-C efficiency compared with of-GIs. As a reason for this, we hypothesize the possibility of the involvement of insulin resistance. Therefore, we consider that insulin resistance should be determined early and that it is important to reduce insulin resistance comprehensively by involving experts.

  18. Use of oral anti-diabetic agents in pregnancy: A pragmatic approach

    Directory of Open Access Journals (Sweden)

    Bharti Kalra

    2015-01-01

    Full Text Available Insulin is the gold standard for treatment of hyperglycemia during pregnancy, when lifestyle measures do not maintain glycemic control during pregnancy. However, recent studies have suggested that certain oral hypoglycemic agents (metformin and glyburide may be safe and be acceptable alternatives. There are no serious safety concerns with metformin, despite it crossing the placenta. Neonatal outcomes are also comparable, with benefit of reductions in neonatal hypoglycemia, maternal hypoglycemia and weight gain, and improved treatment satisfaction. Glibenclamide is more effective in lowering blood glucose in women with gestational diabetes, and with a lower treatment failure rate than metformin. Although generally well-tolerated, some studies have reported higher rates of pre-eclampsia, neonatal jaundice, longer stay in the neonatal care unit, macrosomia, and neonatal hypoglycaemia. There is also paucity of long-term follow-up data on children exposed to oral agents in utero. This review aims to provide an evidence-based approach, concordant with basic and clinical pharmacological knowledge, which will help medical practitioners use oral anti-diabetic agents in a rational and pragmatic manner. Pubmed search was made using Medical Subject Headings (MESH terms "Diabetes" and "Pregnancy" and "Glyburide"; "Diabetes" and "Pregnancy" and "Metformin". Limits were randomized controlled trials (RCTs and meta-analysis. The expert reviews on the topic were also used for discussion. Additional information (studies/review pertaining to discussion under sub-headings like safety during breastfeeding; placental transport; long-term safety data were searched (pubmed/cross-references/expert reviews.

  19. Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5.

    Science.gov (United States)

    Choi, Jang Hyun; Banks, Alexander S; Estall, Jennifer L; Kajimura, Shingo; Boström, Pontus; Laznik, Dina; Ruas, Jorge L; Chalmers, Michael J; Kamenecka, Theodore M; Blüher, Matthias; Griffin, Patrick R; Spiegelman, Bruce M

    2010-07-22

    Obesity induced in mice by high-fat feeding activates the protein kinase Cdk5 (cyclin-dependent kinase 5) in adipose tissues. This results in phosphorylation of the nuclear receptor PPARgamma (peroxisome proliferator-activated receptor gamma), a dominant regulator of adipogenesis and fat cell gene expression, at serine 273. This modification of PPARgamma does not alter its adipogenic capacity, but leads to dysregulation of a large number of genes whose expression is altered in obesity, including a reduction in the expression of the insulin-sensitizing adipokine, adiponectin. The phosphorylation of PPARgamma by Cdk5 is blocked by anti-diabetic PPARgamma ligands, such as rosiglitazone and MRL24. This inhibition works both in vivo and in vitro, and is completely independent of classical receptor transcriptional agonism. Similarly, inhibition of PPARgamma phosphorylation in obese patients by rosiglitazone is very tightly associated with the anti-diabetic effects of this drug. All these findings strongly suggest that Cdk5-mediated phosphorylation of PPARgamma may be involved in the pathogenesis of insulin-resistance, and present an opportunity for development of an improved generation of anti-diabetic drugs through PPARgamma.

  20. Incidence and predictors of hypoglycemia in Japanese patients with type 2 diabetes treated by insulin glargine and oral antidiabetic drugs in real-life: ALOHA post-marketing surveillance study sub-analysis.

    Science.gov (United States)

    Odawara, Masato; Kadowaki, Takashi; Naito, Yusuke

    2014-02-15

    Add-on Lantus® to Oral Hypoglycemic Agents (ALOHA), an observational, non-interventional, 24-week post-marketing surveillance study in Japanese patients with type 2 diabetes (T2DM) having uncontrolled glycemic control, demonstrated that basal supported oral therapy (BOT) with insulin glargine was an effective and safe treatment in real-life clinical practice. We performed subgroup analysis to identify incidence and predictors associated with risk of hypoglycemia. Among 4219 patients with T2DM, 3732 patients were insulin-naïve and 487 patients were insulin non-naïve who switched from other insulin to insulin glargine. All hypoglycemic episodes were counted by physicians' documentation based on patients' reports. Relationships between baseline patient characteristics and glargine-related hypoglycemic episodes were examined by univariate and multivariate analysis. Among 4219 patients, 44 (1.0%) patients experienced hypoglycemic episodes (41 insulin-naïve patients; 3 insulin non-naïve patients), with a rate of incidence 0.035 episodes/patient-years. Majority of patients with hypoglycemia (37 of 44) had just one hypoglycemic episode during study period. Among insulin-naïve patients, incidence of hypoglycemia differed significantly depending on age, diabetic complications, estimated glomerular filtration rate (eGFR), and postprandial plasma glucose (P multivariate adjusted model, poor renal function (eGFR <60 mL/min/1.73 m2) was a statistically significant risk factor (P < 0.05). Our results suggest that BOT using insulin glargine is an option of insulin therapy with 1% risk of hypoglycemia in patients with T2DM with inadequate glycemic control. Patients with low renal function might need a careful follow-up.

  1. An invertebrate hyperglycemic model for the identification of anti-diabetic drugs.

    Science.gov (United States)

    Matsumoto, Yasuhiko; Sumiya, Eriko; Sugita, Takuya; Sekimizu, Kazuhisa

    2011-03-30

    The number of individuals diagnosed with type 2 diabetes mellitus, which is caused by insulin resistance and/or abnormal insulin secretion, is increasing worldwide, creating a strong demand for the development of more effective anti-diabetic drugs. However, animal-based screening for anti-diabetic compounds requires sacrifice of a large number of diabetic animals, which presents issues in terms of animal welfare. Here, we established a method for evaluating the anti-diabetic effects of compounds using an invertebrate animal, the silkworm, Bombyx mori. Sugar levels in silkworm hemolymph increased immediately after feeding silkworms a high glucose-containing diet, resulting in impaired growth. Human insulin and 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, decreased the hemolymph sugar levels of the hyperglycemic silkworms and restored growth. Treatment of the isolated fat body with human insulin in an in vitro culture system increased total sugar in the fat body and stimulated Akt phosphorylation. These responses were inhibited by wortmannin, an inhibitor of phosphoinositide 3 kinase. Moreover, AICAR stimulated AMPK phosphorylation in the silkworm fat body. Administration of aminoguanidine, a Maillard reaction inhibitor, repressed the accumulation of Maillard reaction products (advanced glycation end-products; AGEs) in the hyperglycemic silkworms and restored growth, suggesting that the growth defect of hyperglycemic silkworms is caused by AGE accumulation in the hemolymph. Furthermore, we identified galactose as a hypoglycemic compound in jiou, an herbal medicine for diabetes, by monitoring its hypoglycemic activity in hyperglycemic silkworms. These results suggest that the hyperglycemic silkworm model is useful for identifying anti-diabetic drugs that show therapeutic effects in mammals.

  2. An invertebrate hyperglycemic model for the identification of anti-diabetic drugs.

    Directory of Open Access Journals (Sweden)

    Yasuhiko Matsumoto

    Full Text Available The number of individuals diagnosed with type 2 diabetes mellitus, which is caused by insulin resistance and/or abnormal insulin secretion, is increasing worldwide, creating a strong demand for the development of more effective anti-diabetic drugs. However, animal-based screening for anti-diabetic compounds requires sacrifice of a large number of diabetic animals, which presents issues in terms of animal welfare. Here, we established a method for evaluating the anti-diabetic effects of compounds using an invertebrate animal, the silkworm, Bombyx mori. Sugar levels in silkworm hemolymph increased immediately after feeding silkworms a high glucose-containing diet, resulting in impaired growth. Human insulin and 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR, an AMP-activated protein kinase (AMPK activator, decreased the hemolymph sugar levels of the hyperglycemic silkworms and restored growth. Treatment of the isolated fat body with human insulin in an in vitro culture system increased total sugar in the fat body and stimulated Akt phosphorylation. These responses were inhibited by wortmannin, an inhibitor of phosphoinositide 3 kinase. Moreover, AICAR stimulated AMPK phosphorylation in the silkworm fat body. Administration of aminoguanidine, a Maillard reaction inhibitor, repressed the accumulation of Maillard reaction products (advanced glycation end-products; AGEs in the hyperglycemic silkworms and restored growth, suggesting that the growth defect of hyperglycemic silkworms is caused by AGE accumulation in the hemolymph. Furthermore, we identified galactose as a hypoglycemic compound in jiou, an herbal medicine for diabetes, by monitoring its hypoglycemic activity in hyperglycemic silkworms. These results suggest that the hyperglycemic silkworm model is useful for identifying anti-diabetic drugs that show therapeutic effects in mammals.

  3. Association between glycemic control and antidiabetic drugs in type 2 diabetes mellitus patients with cardiovascular complications

    Directory of Open Access Journals (Sweden)

    Huri HZ

    2015-08-01

    Full Text Available Hasniza Zaman Huri,1,2 Doris Yew Hui Ling,1 Wan Azman Wan Ahmad2,3 1Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Clinical Investigation Centre, University Malaya Medical Centre, Lembah Pantai, Kuala Lumpur, Malaysia; 3Cardiology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Purpose: Cardiovascular disease (CVD is a macrovascular complication in patients with type 2 diabetes mellitus (T2DM. To date, glycemic control profiles of antidiabetic drugs in cardiovascular (CV complications have not been clearly elucidated. Therefore, this study was conducted retrospectively to assess the association of antidiabetic drugs and glycemic control with CV profiles in T2DM patients. The association of concurrent medications and comorbidities with glycemic control was also investigated.Methods: A total of 220 T2DM patients from the University of Malaya Medical Centre, Malaysia, who had at least one CV complication and who had been taking at least one antidiabetic drug for at least 3 months, were included. The associations of antidiabetics, cardiovascular diseases, laboratory parameters, concurrent medications, comorbidities, demographics, and clinical characteristics with glycemic control were investigated.Results: Sulfonylureas in combination (P=0.002 and sulfonylurea monotherapy (P<0.001 were found to be associated with good glycemic control, whereas insulin in combination (P=0.051, and combination biguanides and insulin therapy (P=0.012 were found to be associated with poor glycemic control. Stroke (P=0.044 was the only type of CVD that seemed to be significantly associated with good glycemic control. Other factors such as benign prostatic hyperplasia (P=0.026, elderly patients (P=0.018, low-density lipoprotein cholesterol levels (P=0.021, and fasting plasma glucose (P<0.001 were found to be significantly correlated with good glycemic control

  4. Oral delivery of anticancer drugs

    DEFF Research Database (Denmark)

    Thanki, Kaushik; Gangwal, Rahul P; Sangamwar, Abhay T

    2013-01-01

    The present report focuses on the various aspects of oral delivery of anticancer drugs. The significance of oral delivery in cancer therapeutics has been highlighted which principally includes improvement in quality of life of patients and reduced health care costs. Subsequently, the challenges...... incurred in the oral delivery of anticancer agents have been especially emphasized. Sincere efforts have been made to compile the various physicochemical properties of anticancer drugs from either literature or predicted in silico via GastroPlus™. The later section of the paper reviews various emerging...... trends to tackle the challenges associated with oral delivery of anticancer drugs. These invariably include efflux transporter based-, functional excipient- and nanocarrier based-approaches. The role of drug nanocrystals and various others such as polymer based- and lipid based...

  5. UNIQUE ORAL DRUG DELIVERY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    Raphael M. Ottenbrite; ZHAO Ruifeng; Sam Milstein

    1995-01-01

    An oral drug delivery system using proteinoid microspheres is discussed with respect to its unique dependence on pH. It has been found that certain drugs such as insulin and heparin can be encapsulated in proteinoid spheres at stomach pH's (1-3). These spheres also dissemble at intestinal pH's (6-7) releasing the drug for absorption. Using this technique low molecular weight heparin and human growth hormone have been orally delivered successfully to several animal species. Future work has been proposed to study the interaction and binding of the specific drugs with synthesized oligopeptides.

  6. Insulin Initiation in Insulin-Naïve Korean Type 2 Diabetic Patients Inadequately Controlled on Oral Antidiabetic Drugs in Real-World Practice: The Modality of Insulin Treatment Evaluation Study

    Directory of Open Access Journals (Sweden)

    Sang Soo Kim

    2015-12-01

    Full Text Available BackgroundThe Modality of Insulin Treatment Evaluation (MOTIV study was performed to provide real-world data concerning insulin initiation in Korean type 2 diabetes mellitus (T2DM patients with inadequate glycemic control with oral hypoglycemic agents (OHAs.MethodsThis multicenter, non-interventional, prospective, observational study enrolled T2DM patients with inadequate glycemic control (glycosylated hemoglobin [HbA1c] ≥7.0% who had been on OHAs for ≥3 months and were already decided to introduce basal insulin by their physician prior to the start of the study. All treatment decisions were at the physician's discretion to reflect real-world practice.ResultsA total of 9,196 patients were enrolled, and 8,636 patients were included in the analysis (mean duration of diabetes, 8.9 years; mean HbA1c, 9.2%. Basal insulin plus one OHA was the most frequently (51.0% used regimen. After 6 months of basal insulin treatment, HbA1c decreased to 7.4% and 44.5% of patients reached HbA1c <7%. Body weight increased from 65.2 kg to 65.5 kg, which was not significant. Meanwhile, there was significant increase in the mean daily insulin dose from 16.9 IU at baseline to 24.5 IU at month 6 (P<0.001. Overall, 17.6% of patients experienced at least one hypoglycemic event.ConclusionIn a real-world setting, the initiation of basal insulin is an effective and well-tolerated treatment option in Korean patients with T2DM who are failing to meet targets with OHA therapy.

  7. Cancer, obesity, diabetes, and antidiabetic drugs: is the fog clearing?

    Science.gov (United States)

    Klil-Drori, Adi J; Azoulay, Laurent; Pollak, Michael N

    2017-02-01

    The prevalence of obesity, of type 2 diabetes mellitus (T2DM), and of cancer are all increasing globally. The relationships between these diseases are complex, and thus difficult to elucidate; nevertheless, evidence supports the hypothesis that obesity increases the risks of both T2DM and certain cancers. Further complexity arises from controversial evidence that specific drugs used in the treatment of T2DM increase or decrease cancer risk or influence cancer prognosis. Herein, we review the current evidence from studies that have addressed these relationships, and summarize the methodological challenges that are frequently encountered in such research. We also outline the physiology that links obesity, T2DM, and neoplasia. Finally, we outline the practical principles relevant to the increasingly common challenge of managing patients who have been diagnosed with both diabetes and cancer.

  8. Drug interactions with oral sulphonylurea hypoglycaemic drugs.

    Science.gov (United States)

    Hansen, J M; Christensen, L K

    1977-01-01

    The effect of the oral sulphonylurea hypoglycaemic drugs may be influenced by a large number of other drugs. Some of these combinations (e.g. phenylbutazone, sulphaphenazole) may result in cases of severe hypoglycaemic collapse. Tolbutamide and chlorpropamide should never be given to a patient without a prior careful check of which medicaments are already being given. Similarly, no drug should be given to a diabetic treated with tolbutamide and chlorpropamide without consideration of the possibility of interaction phenomena.

  9. Heart failure hospitalization risk associated with use of two classes of oral antidiabetic medications: an observational, real-world analysis.

    Science.gov (United States)

    Gautam, Santosh; Agiro, Abiy; Barron, John; Power, Thomas; Weisman, Harry; White, Jeff

    2017-07-31

    Newer oral antidiabetic drug classes are expanding treatment options for type 2 diabetes mellitus (T2DM); however, concerns remain. The objective was to assess relative risk of heart failure hospitalization of sodium-glucose co-transporter-2 (SGLT2) and dipeptidyl peptidase-4 (DPP4) inhibitors in T2DM patients. This retrospective observational study used a national commercially insured claims database. Adults (>18 years) with T2DM newly starting SGLT2 or DPP4 medication between April 2013 and December 2014 were included. Depending on their index fill, patients were grouped into either SGLT2 or DPP4 medication class cohorts. The primary outcome was hospitalization for heart failure and the risk was assessed using Cox regression models. Propensity score matching (1:2 ratio) was used to adjust for potential confounders. Analyses were also stratified by the presence of baseline diabetes complication and age (heart failure hospitalization was lower among SGLT2 users in comparison with matched DPP4 users (2.0% SGLT2 vs 3.1% DPP4; adjusted hazard ratio [aHR] 0.68; 95% confidence interval [CI] 0.54-0.86; p = .001). However, the stratified analyses revealed no risk difference among the majority of the analyzed patients, i.e., those aged heart failure was significantly lower for patients initiating an SGLT2 compared with a DPP4 medication, specifically among older patients and those with diabetes complication.

  10. Pathways targeted by antidiabetes drugs are enriched for multiple genes associated with type 2 diabetes risk.

    Science.gov (United States)

    Segrè, Ayellet V; Wei, Nancy; Altshuler, David; Florez, Jose C

    2015-04-01

    Genome-wide association studies (GWAS) have uncovered >65 common variants associated with type 2 diabetes (T2D); however, their relevance for drug development is not yet clear. Of note, the first two T2D-associated loci (PPARG and KCNJ11/ABCC8) encode known targets of antidiabetes medications. We therefore tested whether other genes/pathways targeted by antidiabetes drugs are associated with T2D. We compiled a list of 102 genes in pathways targeted by marketed antidiabetic medications and applied Gene Set Enrichment Analysis (MAGENTA [Meta-Analysis Gene-set Enrichment of variaNT Associations]) to this gene set, using available GWAS meta-analyses for T2D and seven quantitative glycemic traits. We detected a strong enrichment of drug target genes associated with T2D (P = 2 × 10(-5); 14 potential new associations), primarily driven by insulin and thiazolidinedione (TZD) targets, which was replicated in an independent meta-analysis (Metabochip). The glycemic traits yielded no enrichment. The T2D enrichment signal was largely due to multiple genes of modest effects (P = 4 × 10(-4), after removing known loci), highlighting new associations for follow-up (ACSL1, NFKB1, SLC2A2, incretin targets). Furthermore, we found that TZD targets were enriched for LDL cholesterol associations, illustrating the utility of this approach in identifying potential side effects. These results highlight the potential biomedical relevance of genes revealed by GWAS and may provide new avenues for tailored therapy and T2D treatment design. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  11. Effect of insulin detemir versus neutral protamine zinc insulin combined with oral anti-diabetes drugs in treating type 2 diabetes mellitus%地特胰岛素对比中性鱼精蛋白锌胰岛素联合口服降糖药治疗2型糖尿病的疗效和安全性观察

    Institute of Scientific and Technical Information of China (English)

    吕蕾; 郭俊杰; 郭晓霏

    2012-01-01

    Objective To compare of effect of insulin detemir (Det) versus neutral protamine hagedorn (NPI1) combined with oral anti-diabetes drugs (OADs) in treating type 2 diabetes mellitus (T2DM). Methods The 60 T2DM patients divided into two groups were treated with Det + OADs versus NPH + OADs respectively. The comparisons of fasting plasma glucose (FPG), two-hour postprandial plasma glucose (2 hPG), incidence of hypoglycemia, body mass index (BMI), and hemoglobin A1c (HbA1c) between the two groups before versus after treatment were performed to observe the final effect. Results The levels of FPG, 2 hPG, and HbA1c of the two groups were decreased after treatment for 12 weeks, while the decrease in the Det+OADs group was more significant (P<0. 05). The Det+OADs group was superior to the NPH + OADs group in the BMI control (P<0. 05) and less hypoglycemia. Conclusion Comparing with NPH+ OADs, the effect of Det+OADs is better in treating T2DM with less incidence of hypoglycemia and less influence on body weight.%目的 探讨地特胰岛素(Det)对比中性鱼精蛋白锌胰岛素(NPH)联合口服降糖药(OADs)治疗T2DM的疗效和安全性.方法 选择60例T2DM患者分别应用Det和NPH联合OADs治疗,比较两组治疗前后FPG、2 hPG、低血糖事件发生、BMI及HbA1 c变化.结果 两组患者治疗12周后FPG、2 hPG、HbA1 c均较治疗前下降(P<0.05),但Det组下降更显著(P<0.05),Det组对BMI控制优于NPH组(P<0.05),低血糖发生率低.结论 与NPH相比,Det联合OADs治疗T2DM疗效更好,低血糖发生率低,对体重影响小.

  12. Antidiabetic Effect of Galantamine: Novel Effect for a Known Centrally Acting Drug.

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    Mennatallah A Ali

    Full Text Available The cholinergic anti-inflammatory pathway is one of the putative biochemical pathways that link diabetes with Alzheimer disease. Hence, we aimed to verify the potential antidiabetic effect of galantamine, unveil the possible mechanisms and evaluate its interaction with vildagliptin. The n5-STZ rat model was adopted and the diabetic animals were treated with galantamine and/or vildagliptin for 4 weeks. Galantamine lowered the n5-STZ-induced elevation in body weight, food/water intake, serum levels of glucose, fructosamine, and ALT/AST, as well as AChE in the tested organs. Moreover, it modulated successfully the lipid profile assessed in serum, liver, and muscle, and increased serum insulin level, as well as % β-cell function, in a pattern similar to that of vildagliptin. Additionally, galantamine confirmed its antioxidant (Nrf2, TAC, MDA, anti-inflammatory (NF-κB, TNF-α, visfatin, adiponectin and anti-apoptotic (caspase-3, cytochrome c capabilities by altering the n5-STZ effect on all the aforementioned parameters. On the molecular level, galantamine/vildagliptin have improved the insulin (p-insulin receptor, p-Akt, GLUT4/GLUT2 and Wnt/β-catenin (p-GSK-3β, β-catenin signaling pathways. On almost all parameters, the galantamine effects surpassed that of vildagliptin, while the combination regimen showed the best effects. The present results clearly proved that galantamine modulated glucose/lipid profile possibly through its anti-oxidant, -apoptotic, -inflammatory and -cholinesterase properties. These effects could be attributed partly to the enhancement of insulin and Wnt/β-catenin signaling pathways. Galantamine can be strongly considered as a potential antidiabetic agent and as an add-on therapy with other oral antidiabetics.

  13. Adverse drug reaction monitoring of newer oral anti diabetic drugs – a pharmacovigilance perspective

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    Ankita Bhattacharjee

    2016-04-01

    Full Text Available Objective: To monitor and evaluate adverse drug reactions (ADRs of newer oral anti-diabetic drugs in type II diabetics by spontaneous/solicited ADR monitoring.Material and methods: Two hundred and thirty two diabetic patients on newer oral antidiabetic drugs were evaluated prospectively in a cross-sectional study over a period of eighteen months. All patients were followed up for ADRs which were evaluated for incidence, frequency, severity and causality. ADR severity was graded according to University of Virginia Health System Adverse Drug Reaction Reporting program criteria and causality assessment was done using WHO-UMC scale.Results: 190 out of 232 patients (42 patients lost to follow up were evaluated. ADRs were observed in 34 cases (17.9%. Most common ADRs were gastrointestinal (44.2% followed by musculoskeletal (17.6%, metabolic (14.7%, infections (5.9% and others (17.6%. The maximal frequency of ADRs was seen with sitagliptin (6.4% followed by vildagliptin(3.8%, saxagliptin(2.7%, saroglitazar(2.1%, linagliptin(1.6%, canagliflozin(1.6%. 25(73.5%, 8(23.5% and 1(3% ADRs were mild, moderate and severe respectively. 24(70% ADRs were classified as possible, 9(27% probable and 1(3% unlikely on causality assessment. Conclusion: Newer oral antidiabetic drugs like gliptins and SGLT-2 inhibitors have potential to cause ADRs. Gastro-intestinal, musculoskeletal, metabolic were most common ADRs. Active pharmacovigilance should be carried out for risk identification and management. 

  14. Replicate study design in bioequivalency assessment, pros and cons: bioavailabilities of the antidiabetic drugs pioglitazone and glimepiride present in a fixed-dose combination formulation.

    Science.gov (United States)

    Karim, Aziz; Zhao, Zhen; Slater, Margaret; Bradford, Dawn; Schuster, Jennifer; Laurent, Aziz

    2007-07-01

    An open-label, randomized, 2-sequence, 4-period crossover (7-day washout period between treatment), replicate design study was conducted in 37 healthy subjects to assess intersubject and intrasubject variabilities in the peak (Cmax) and total (AUC) exposures to 2 oral antidiabetic drugs, pioglitazone and glimepiride, after single doses of 30 mg pioglitazone and 4 mg glimepiride, given under fasted state, as commercial tablets coadministered or as a single fixed-dose combination tablet. Variabilities for AUC(infinity) for coadministered and fixed-dose combination treatments were similar: 16% to 19% (intra) and 23% to 25% (inter) for pioglitazone and 18% to 19% (intra) and 29% to 30% for glimepiride (inter, excluding 1 poor metabolizer). Fixed-dose combination/coadministered least squares mean ratios of >or=0.86 and the 90% confidence intervals of these ratios for pioglitazone and glimepiride of between 0.80 and 1.25 for Cmax, AUC(lqc), and AUC(infinity) met the bioequivalency standards. Gender analysis showed that women showed mean of 16% and 30% higher exposure than men for glimepiride (excluding 1 poor metabolizer) and pioglitazone, respectively. There was considerable overlapping in the AUC(infinity) values, making gender-dependent dosing unnecessary. Patients taking pioglitazone and glimepiride as cotherapy may replace their medication with a single fixed-dose combination tablet containing these 2 oral antidiabetic drugs.

  15. [A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus].

    Science.gov (United States)

    Ozawa, Hikaru; Murai, Yuriko; Ozawa, Terutaka

    2003-01-01

    recombinant products prevailed throughout the 1990s. Human insulin analogues (i.e., Insulin lispro and Insulin aspart) appeared in 2001. These are applied for after-meal glycosmia owing to their ultrarapid onset of activity. Self-injection by DM patients was legalized in 1981. To make the infection technique sure and easy, cartridge (pen-type) and disposable kit-type needles were devised in the 1990s. 2) Oral hypoglycemic drugs: Instead of the exclusive parenteral usage of insulins, there was also demand for oral dosage forms. The first of the sulfonyrlurea (SU) group, BZ-55, was used for DM clinically in 1955 in Germany. But it was soon withdrawn because of its antibacterial action. This led to the development of various SU groups. Tolbutamide (1956), chlorpropamide (1959), acetohexamide (1964) and tolazamide (1961) were introduced to Japan as first-generation SUs. Then glyclopyramide (Kyorin, 1965), glybenclamide (1971), gliclazide (1984) and glimepiride (1999) appeared as the second-generation SUs. These were used orally for Type 2 diabetes. Biguanide (BG) group, phenformin HC1 (1959), metformin HC1 (1961) and buformin HC1 (1961) had also been in use by oral treatment of Type 2 diabetes. SU appears to act by increasing the sensitivity of b-cells, which secrete insulin. BG probably exerts by increasing glucose transport across the membranes of target organs. 3) New types of antidiabetic drugs: a-Glucosidase inhibitors (i.e., acarbose: Bayer, 1993; and voglibose: Takeda, 1994) act on hyperglycemia after meals by decreasing glucose absorption. Thiazolidinedione compounds, such as troglitazone (Sankyo, 1995) and pioglitazone HC1 (Takeda, 1994) act by increasing the insulin sensitivity of the target tissues. These are useful for Type 2 DM patients when SUs are ineffective. Nevertheless, troglitazone was discontinued in 2000 due to severe liver damage. Nateglinide (Ajinomoto Co., 1999), which is a D-phenylalanine derivative acting similar to SUs, is useful orally for after

  16. Developing imprinted polymer nanoparticles for the selective separation of antidiabetic drugs.

    Science.gov (United States)

    Haq, Isma; Mujahid, Adnan; Afzal, Adeel; Iqbal, Naseer; Bajwa, Sadia Zafar; Hussain, Tajamal; Shehzad, Khurram; Ashraf, Hadia

    2015-10-01

    In this study, new molecularly imprinted polymer (MIP) nanoparticles are designed for selective recognition of different drugs used for the treatment of type 2 diabetes mellitus, i.e. sitagliptin (SG) and metformin (MF). The SG- and MF-imprinted polymer nanoparticles are synthesized by free-radical initiated polymerization of the functional monomers: methacrylic acid and methyl methacrylate; and the crosslinker: ethylene glycol dimethacrylate. The surface morphology of resultant MIP nanoparticles is studied by atomic force microscopy. Fourier transform infrared spectra of MIP nanoparticles suggest the presence of reversible, non-covalent interactions between the template and the polymer. The effect of pH on the rebinding of antidiabetic drugs with SG- and MF-imprinted polymers is investigated to determine the optimal experimental conditions. The molecular recognition characteristics of SG- and MF-imprinted polymers for the respective drug targets are determined at low concentrations of SG (50-150 ppm) and MF (5-100 ppm). In both cases, the MIP nanoparticles exhibit higher binding response compared to non-imprinted polymers. Furthermore, the MIPs demonstrate high selectivity with four fold higher responses toward imprinted drugs targets, respectively. Recycled MIP nanoparticles retain 90% of their drug-binding efficiency, which makes them suitable for successive analyses with significantly preserved recognition features.

  17. Electrochemical determination of some antidiabetic drugs for type 2 diabetic patients.

    Science.gov (United States)

    Badawy, Waheed A; El-Ries, Mohammed A; Mahdi, Inas M

    2010-06-30

    Quantitative determination of rosiglitazone, pioglitazone, glimepiride and glyburide as antidiabetic drugs for type 2 diabetic patients was performed conveniently and economically using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Carbon paste (CPE) and glassy carbon (GCE) electrodes were successfully used as sensors for these drugs in Briton-Robinson (B-R) as buffer solution. The preparation of CPE and the GCE as ion selective electrodes is based on the construction of 10% standard drug ion pair with reineckate or tungstophosphate imbedded as electroactive material. Working standards were freshly prepared just before the assay by dilution from a 10(-2)mol L(-1) drug stock solution. At a scan rate of 100 mV s(-1) the cyclic voltammograms showed a well defined anodic peak with high selectivity. The DVP gave a reproducible well defined diffusion controlled peak for each drug at a scan rate of 10 mV s(-1). The oxidation peaks were used to determine the tested drug concentrations. The quantitative determination of the four drugs in their pharmaceutical preparations by the proposed electrochemical technique was found to be identical with the values obtained by the standard HPLC method. A mean % recovery of 100+/-1 was obtained and the % relative standard deviation was 1.62 indicating the high precision of the method and the confidence in its repeatability. The proposed electroanalytical technique using either the CPE or the GCE is economic, selective and can be applied for both the qualitative and quantitative determination of the drugs in their pharmaceutical preparations, without special drug separation. Copyright 2010 Elsevier B.V. All rights reserved.

  18. Why Antidiabetic Vanadium Complexes are Not in the Pipeline of "Big Pharma" Drug Research? A Critical Review.

    Science.gov (United States)

    Scior, Thomas; Guevara-Garcia, Jose Antonio; Do, Quoc-Tuan; Bernard, Philippe; Laufer, Stefan

    2016-01-01

    Public academic research sites, private institutions as well as small companies have made substantial contributions to the ongoing development of antidiabetic vanadium compounds. But why is this endeavor not echoed by the globally operating pharmaceutical companies, also known as "Big Pharma"? Intriguingly, today's clinical practice is in great need to improve or replace insulin treatment against Diabetes Mellitus (DM). Insulin is the mainstay therapeutically and economically. So, why do those companies develop potential antidiabetic drug candidates without vanadium (vanadium- free)? We gathered information about physicochemical and pharmacological properties of known vanadium-containing antidiabetic compounds from the specialized literature, and converted the data into explanations (arguments, the "pros and cons") about the underpinnings of antidiabetic vanadium. Some discoveries were embedded in chronological order while seminal reviews of the last decade about the Medicinal chemistry of vanadium and its history were also listed for further understanding. In particular, the concepts of so-called "noncomplexed or free" vanadium species (i.e. inorganic oxido-coordinated species) and "biogenic speciation" of antidiabetic vanadium complexes were found critical and subsequently documented in more details to answer the question.

  19. Binding studies of the antidiabetic drug, metformin to calf thymus DNA using multispectroscopic methods

    Science.gov (United States)

    Shahabadi, Nahid; Heidari, Leila

    2012-11-01

    Interaction between antidiabetic drug, Metformin and calf thymus DNA (CT-DNA) in (50 mM Tris-HCl) buffer were studied by UV-Visible absorption, fluorescence, CD spectroscopy and viscosity measurements. In fluorimetric studies, the enthalpy and entropy of the reaction between the drug and CT-DNA showed that the reaction is exothermic (ΔH = -35.4522 kJ mol-1; ΔS = -49.9523 J mol-1 K-1). The competitive binding studies showed that the drug could release Hoechst 33258 completely. The complex showed absorption hyperchromism in its UV-Vis spectrum with DNA. The calculated binding constant, Kb, obtained from UV-Vis absorption studies was 8.3 × 104 M-1. Moreover, the changes in the CD spectra in the presence of the drug show stabilization of the right-handed B form of CT-DNA. Finally, viscosity measurements revealed that the binding of the complex with CT-DNA could be surface binding, mainly due to groove binding.

  20. Reactivity-activity relationships of oral anti-diabetic vanadium complexes in gastrointestinal media: an X-ray absorption spectroscopic study.

    Science.gov (United States)

    Levina, Aviva; McLeod, Andrew I; Kremer, Lauren E; Aitken, Jade B; Glover, Christopher J; Johannessen, Bernt; Lay, Peter A

    2014-10-01

    The reactions of oral V(V/IV) anti-diabetic drugs within the gastrointestinal environment (particularly in the presence of food) are a crucial factor that affects their biological activities, but to date these have been poorly understood. In order to build up reactivity-activity relationships, the first detailed study of the reactivities of typical V-based anti-diabetics, Na3V(V)O4 (A), [V(IV)O(OH2)5](SO4) (B), [V(IV)O(ma)2] (C, ma = maltolato(-)) and (NH4)[V(V)(O)2(dipic)] (D, dipic = pyridine-2,5-dicarboxylato(2-)) with simulated gastrointestinal (GI) media in the presence or absence of food components has been performed by the use of XANES (X-ray absorption near edge structure) spectroscopy. Changes in speciation under conditions that simulate interactions in the GI tract have been discerned using correlations of XANES parameters that were based on a library of model V(V), V(IV), and V(III) complexes for preliminary assessment of the oxidation states and coordination numbers. More detailed speciation analyses were performed using multiple linear regression fits of XANES from the model complexes to XANES obtained from the reaction products from interactions with the GI media. Compounds B and D were relatively stable in the gastric environment (pH ∼ 2) in the absence of food, while C was mostly dissociated, and A was converted to [V10O28](6-). Sequential gastric and intestinal digestion in the absence of food converted A, B and D to poorly absorbed tetrahedral vanadates, while C formed five- or six-coordinate V(V) species where the maltolato ligands were likely to be partially retained. XANES obtained from gastric digestion of A-D in the presence of typical food components converged to that of a mixture of V(IV)-aqua, V(IV)-amino acid and V(III)-aqua complexes. Subsequent intestinal digestion led predominantly to V(IV) complexes that were assigned as citrato or complexes with 2-hydroxyacidato donor groups from other organic compounds, including certain

  1. LOW RISK OF CARDIOVASCULAR DISEASES WITH METFORMIN COMPARED WITH OTHER ANTI-DIABETIC DRUGS IN PATIENTS WITH TYPE 2 DIABETES

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    Prathima Raj Dara

    2016-07-01

    Full Text Available BACKGROUND Diabetes is treatable, yet not withstanding when glucose levels are under control. It significantly increase the risk of coronary illness and stroke. Especially, type 2 diabetes may have the accompanying conditions that add to their danger for creating cardiovascular illness, for example, hypertension, weight, and abdominal cholesterol. This study to investigate the risk of cardiovascular malady (CVD in people with diabetes mellitus treated with metformin or other antidiabetic medications. SUBJECTS AND METHODS This was an observational study conducted in the Department of Medicine at Government General Hospital, Nizamabad. 500 patients were aged between 60 and below individuals diagnosed with cardiovascular problem irrespective of metformin or other anti-diabetic drugs from past years. Patient’s comparison with previous use of metformin or other anti-diabetic drugs among the individuals and calculated the risk of cardiovascular disease who is on metformin or anti-diabetic drugs. RESULTS In comparison with metformin, long-term use of other than metformin were at greater risk of developing CVD (Adjusted OR (AOR=0.83, 95% CI=1.12-2.60, but there was no consistent trend with increasing number of prescriptions. Long-term use of other antidiabetic drugs such as sulphonylurea (AOR=0.80, 95% CI=0.72-1.42, thiazolidinediones (AOR=0.69, 95% CI=0.31-2.40, or meglitinides (AOR=0.61, 95% CI=0.58-1.73 was showed related risk of developing CVD. CONCLUSION Long-term utilization of sulphonylurea, thiazolidinediones, or meglitinides was showed risk of developing CVD. There was a recommendation of a slightly bring down risk of CVD in long-term use of metformin.

  2. COST ANALYSIS OF ANTIDIABETIC DRUGS FOR DIABETES MELLITUS OUTPATIENT IN KODYA YOGYAKARTA HOSPITAL

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    TRI MURTI ANDAYANI

    2007-01-01

    Full Text Available Diabetes mellitus is a chronic disorder that has been recognised by the Indonesian government as a major public health problem with far reaching consequences not just for its adverse impact on the healthof Indonesians, but also for the economic burden it places on the healthcare systems. The objectives of this study were to describe the healthcare cost for outpatient diabetes mellitus treatment and to examine the cost of different classes of antidiabetic drug. The medical records of Type 2 diabetes mellitus outpatients without compelling indication were retrospectively reviewed. Data was collected for patients treated from January 1st to December 31st, 2004 in Kodya Yogyakarta Hospital. Data collected includedpatient demographics, drug acquisition cost, medical consultation cost and laboratory cost. We analysed charts of 100 consecutive patients, of whom 71% are women and 29% are men. The average age ofpatient was 61.2 ± 13.7 years. The monthly mean cost of Type 2 diabetes mellitus was found to be equivalent to USD19.97 ± 13.71. Most of the direct medical costs were spent on drugs (96.4%. Bloodglucose control using combination therapy was more frequently attained in patients taking glibenclamide and metformin (25%. The combination of gliquidone-metformin-acarbose (21% was themost expensive, which was equivalent to USD39.44. The potential saving was 6.10% of total drug cost if generic substitutions were prescribed for diabetes mellitus in place of more expensive drugs. Inconclusion, we identified that the costs of diabetes mellitus outside of hospitals are mainly dependent on the expenses with blood glucose-lowering drugs.

  3. Pharmacoeconomic analysis on six kinds of regimens using oral antidiabetic drugs in national essential medicines%国家基本药物中口服降糖药6种用药方案的药物经济学分析

    Institute of Scientific and Technical Information of China (English)

    江丽欢; 陈月婵; 霍彩凤

    2013-01-01

      目的:运用药物经济学方法评价国家基本药物中口服降糖药的6种用药方案治疗2型糖尿病的药物经济学效果,为治疗2型糖尿病的药物选择提供参考。方法:将我院2011年3月–2012年8月在门诊治疗的300例2型糖尿病患者平均分为6组,每组50例,分别给予二甲双胍(A组),格列齐特缓释胶囊(B组),格列美脲(C组),二甲双胍+格列本脲(D组),二甲双胍+格列美脲(E组),二甲双胍+格列齐特缓释胶囊(F组)进行治疗。观察12周后空腹血糖、餐后2 h血糖及HbA1c,利用成本-效果分析方法,比较其药物经济学效果。结果:治疗12周后,A、B、C、D、E、F组的成本分别为70.56、198.24、136.08、42.84、171.36、233.52元;总有效率分别为86.0%、88.0%、88.0%、84.0%、94.0%、92.0%。经过成本-效果分析,D组C/E为51.00,最小,E组ΔC/ΔE值为12.85,A组ΔC/ΔE值为13.86。结论:从药物经济学的角度分析,D组治疗2型糖尿病方案最经济,但是E组疗效最佳,单一用药方案中A组是最佳选择,在临床治疗中应根据具体情况合理选择。%  Objective:To evaluate the pharmacoeconomic effect on the six kinds of regimens using oral antidiabetic drugs in national essential medicines for treating type 2 diabetes mellitus, and provide reference for drug choice. Methods:A total of 300 type 2 diabetic patients in outpatient of our hospital collected from March 2011 to August 2012 were assigned into 6 groups with 50 cases in each group. Metformin (group A), gliclazide sustained release tablets (group B), glimepiride (group C), metformin and glibenclamide (group D), metformin and glimepiride (group E) and metformin and gliclazide sustained release tablets (group F) were given in different groups, respectively. The treatment effect was observed 12 weeks later by evaluating fasting blood glucose, postprandial 2 h blood glucose and HbA1c

  4. Comparison of the Efficacy of Glimepiride, Metformin, and Rosiglitazone Monotherapy in Korean Drug-Naïve Type 2 Diabetic Patients: The Practical Evidence of Antidiabetic Monotherapy Study

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    Kun Ho Yoon

    2011-02-01

    Full Text Available BackgroundAlthough many anti-diabetic drugs have been used to control hyperglycemia for decades, the efficacy of commonly-used oral glucose-lowering agents in Korean type 2 diabetic patients has yet to be clearly demonstrated.MethodsWe evaluated the efficacy of glimepiride, metformin, and rosiglitazone as initial treatment for drug-naïve type 2 diabetes mellitus patients in a 48-week, double-blind, randomized controlled study that included 349 Korean patients. Our primary goal was to determine the change in HbA1c levels from baseline to end point. Our secondary goal was to evaluate changes in fasting plasma glucose (FPG levels, body weight, frequency of adverse events, and the proportion of participants achieving target HbA1c levels.ResultsHbA1c levels decreased from 7.8% to 6.9% in the glimepiride group (P<0.001, from 7.9% to 7.0% in the metformin group (P<0.001, and from 7.8% to 7.0% (P<0.001 in the rosiglitazone group. Glimepiride and rosiglitazone significantly increased body weight and metformin reduced body weight during the study period. Symptomatic hypoglycemia was more frequent in the glimepiride group and diarrhea was more frequent in the metformin group.ConclusionThe efficacy of glimepiride, metformin, and rosiglitazone as antidiabetic monotherapies in drug-naïve Korean type 2 diabetic patients was similar in the three groups, with no statistical difference. This study is the first randomized controlled trial to evaluate the efficacy of commonly-used oral hypoglycemic agents in Korean type 2 diabetic patients. An additional subgroup analysis is recommended to obtain more detailed information.

  5. C{sub 18}-attached membrane funnel-based spray ionization mass spectrometry for quantification of anti-diabetic drug from human plasma

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wan [Department of Chemistry, The Chinese University of Hong Kong, Hong Kong Special Administrative Region (Hong Kong); Chen, Xiangfeng, E-mail: xiangfchensdas@163.com [Department of Chemistry, The Chinese University of Hong Kong, Hong Kong Special Administrative Region (Hong Kong); Shandong Analysis and Test Centre, Shandong Academy of Sciences, Jinan, Shandong (China); Wong, Y.-L. Elaine; Hung, Y.-L. Winnie; Wang, Ze; Deng, Liulin [Department of Chemistry, The Chinese University of Hong Kong, Hong Kong Special Administrative Region (Hong Kong); Dominic Chan, T.-W., E-mail: twdchan@cuhk.edu.hk [Department of Chemistry, The Chinese University of Hong Kong, Hong Kong Special Administrative Region (Hong Kong)

    2016-08-24

    In this work, sorbent-attached membrane funnel-based spray ionization mass spectrometry was explored for quantitative analysis of anti-diabetic drugs spiked in human plasma. C{sub 18}-attached membrane funnel was fabricated for in situ extraction and clean-up to alleviate matrix suppression effect in the ionization process. Repaglinide was used as a target analyte of anti-diabetic drugs. Under optimal working conditions, good linearity (R{sup 2} > 0.99) was obtained in the concentration range of 1–100 ng mL{sup −1}. The method detection limit of target drugs spiked in the human plasma was around 0.30 ng mL{sup −1}. Through the application of an isotope-labeled internal standard, the signal fluctuation caused by residual background matrices was largely alleviated and the precision of measurement (RSD) was below 15%. The recovery of repaglinide for 5, 25, and 100 ng mL{sup −1} of spiked human plasma matrixes ranged from 87% to 112%. The developed method was successfully applied to determine repaglinide in plasma volunteers who orally received a dose of drug association. Our results demonstrated that membrane funnel-based spray is a simple and sensitive method for rapid screening analysis of complex biological samples. - Highlights: • Sorbent attached membrane funnel based spray platform was used for drug determination in human plasma. • The matrix suppression effect of human plasma was largely eliminated. • The method was applied to determine repaglinide in plasma volunteers. • Membrane funnel-based spray is promising for analysis of biological samples.

  6. Metformin-loaded BSA nanoparticles in cancer therapy: a new perspective for an old antidiabetic drug.

    Science.gov (United States)

    Jose, Pinkybel; Sundar, K; Anjali, C H; Ravindran, Aswathy

    2015-03-01

    Clinical and experimental data suggest that there is a strong association between type II diabetic mellitus and pancreatic cancer. The present study focuses on exploring the anticancer and antidiabetic properties of metformin-loaded bovine serum albumin nanoparticles (BSA NPs) on (MiaPaCa-2) pancreatic carcinoma cell lines. Albumin nanoparticles were synthesized using coacervation method and the average size of the particles was found to be 97 nm. The particles were stable and showed a spherical morphology with narrow size distribution. We investigated the impact of two stages characterized in type II diabetes mellitus (hyperglycemia and hyperinsulinemia) on the proliferation of MiaPaCa-2 cells and compared the inhibitory effects of bare metformin to that of MET-BSA NPs. Further, different concentrations of insulin and glucose were added along with bare metformin, bare BSA, and metformin encapsulated BSA carrier on MiaPaCa-2 cells to check the strong association between type II diabetes and pancreatic cancer. The results revealed that MET-BSA NPs showed more toxicity when compared with drug and carrier individually.

  7. Noninsulin Antidiabetic Drugs for Patients with Type 2 Diabetes Mellitus: Are We Respecting Their Contraindications?

    Directory of Open Access Journals (Sweden)

    Irene Ruiz-Tamayo

    2016-01-01

    Full Text Available Aim. To assess prescribing practices of noninsulin antidiabetic drugs (NIADs in T2DM with several major contraindications according to prescribing information or clinical guidelines: renal failure, heart failure, liver dysfunction, or history of bladder cancer. Methods. Cross-sectional, descriptive, multicenter study. Electronic medical records were retrieved from all T2DM subjects who attended primary care centers pertaining to the Catalan Health Institute in Catalonia in 2013 and were pharmacologically treated with any NIAD alone or in combination. Results. Records were retrieved from a total of 255,499 pharmacologically treated patients. 78% of patients with some degree of renal impairment (glomerular filtration rate (GFR < 60 mL/min were treated with metformin and 31.2% with sulfonylureas. Even in the event of severe renal failure (GFR < 30 mL/min, 35.3% and 22.5% of patients were on metformin or sulfonylureas, respectively. Moreover, metformin was prescribed to more than 60% of patients with moderate or severe heart failure. Conclusion. Some NIADs, and in particular metformin, were frequently used in patients at high risk of complications when they were contraindicated. There is a need to increase awareness of potential inappropriate prescribing and to monitor the quality of prescribing patterns in order to help physicians and policymakers to yield better clinical outcomes in T2DM.

  8. 口服降糖药不良反应对2型糖尿病患者心理健康和生活质量的影响%Association between side effects of oral anti-diabetic drugs and self- reported mental health and quality of life among patients with type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    陈宗存; 张少玲; 严励; 吴木潮; 陈黎红; 纪立农

    2011-01-01

    目的 探讨口服降糖药常见不良反应低血糖和体重增加对2型糖尿病患者心理建康和生存质量的影响.方法 全国16家三甲医院于2007年1至6月对486例2型糖尿病患者采用统一的患者问卷(AP RECAP-DM研究)进行病史采集,以低血糖担忧勘测量表(HFS-Ⅱ)测量患者治疗后对低血糖的担忧状况,欧洲生存质量五维量表(EQ-5D)测量患者治疗后的健康相关生存质量.结果 203例(41.8%)发生低血糖,其中18例(8.8%)为严重或极严重低血糖.93例(19.2%)有体重增加,其中11例(11.7%)体重增加超过5 kg.发生低血糖组HFS-Ⅱ分值高于无低血糖组[7.00(2.00~19.00)比0.00(0.00~7.00),P<0.01]而EQ-5D健康指数低于未发生低血糖组(0.90±0.12比0.93±0.13,P=0.003),其中严重或极严重低血糖组HFS-Ⅱ分值高于轻度低血糖组[20.00(8.00~30.00)比5.00(0.00~14.00),P<0.01].回归分析显示,HFS-Ⅱ分值与低血糖反应呈正相关(β=5.78,P<0.01),EQ-5D健康指数与低血糖反应呈负相关(β=-0.04,P<0.05),其中相对于轻度低血糖,严重低血糖或极严重低血糖组的HFS-Ⅱ分值较高(β=10.92,P<0.01).结论 在口服降糖药治疗过程中存在着较高的低血糖发生风险,与自我感觉不良和负性心理健康相关,有可能影响糖尿病远期预后.%Objective To examine the association between the side effects of oral anti-diabetic drugs (OAD) and self-reported mental health and quality of life among patients with type 2 diabetes mellitus (T2DM). Methods An observational, cross-sectional multicenter study with a retrospective medical chart review was conducted at 16 medical centers from around China. The T2DM patients were followed-up and treated with OAD alone prior to the index visit from January to September 2007. All subjects were ≥30 years old at the time of T2DM diagnosis and had received monotherapy or combination therapy of OAD for at least 6 months. Health-related quality of life was measured

  9. 口服降糖药联合甘精胰岛素及餐前一次门冬胰岛素的治疗达标研究——1+1研究%Efficacy of the addition of a single bolus of insulin glulisine in combination with basal insulin glargine and oral antidiabetic drugs

    Institute of Scientific and Technical Information of China (English)

    天津市"1+1研究"协作组

    2011-01-01

    目的 观察2型糖尿病患者经口服降糖药联合甘精胰岛素治疗仍未达标时,于餐前增加1次门冬胰岛素的有效性、安全性和可行性.方法 采用多中心、开放、自身对照的方法.59例经口服降糖药及甘精胰岛素治疗而糖化血红蛋白(Hb)A1c>6.5%但<9%的患者,于主餐前加用门冬胰岛素治疗16周.结果 16周后,患者HbA1c由治疗前的(8.04±0.58)%降至(6.78±0.30)%(P<0.01),其中13例(22.03%)达到≤6.5%,43例(72.88%)达到<7.0%.早餐前、午餐前及晚餐前注射门冬胰岛素组3餐后血糖均较前明显降低,HbA1c分别为(6.70±0.29)%,(6.80±0.32)%及(6.90±0.21)%.患者低血糖发生率为0.38次/(患者·年),无夜间低血糖和严重低血糖事件发生.患者平均体重及体重指数均明显下降.结论 对于口服降糖药联合甘精胰岛素治疗血糖控制欠佳的2型糖尿病患者,于主餐前增加1次门冬胰岛素可以有效、安全地降低患者血糖,提高达标率,且具有较高可行性.%Objective To investigate the efficacy,safety and feasibility of the addition of a single bolus of insulin glulisine before meal, in combination with basal insulin glargine and oral antidiabetic drugs (OADs) in the treatment of patients with type 2 diabetes. Methods 59 patients with type 2 diabetes who were suboptimally controlled (HbA1c 6.5%-9.0% )on their previous glargine and OADs regimen were included in this 16 weeks, multicentre, open-label and self-control study. A single injection of glulisine was added,at main mealtime,to their existing therapy. Results HbA1c was decreased from (8.04 ±0.58)% to (6.78 ±0.30) % after 16 weeks(P <0.01 ). 13 patients(22.03% ) obtained the target of HbA1c ≤6.5%,43 patients (72.88%)obtained the target of HbA1c <7.0%. Glulisine given at breakfast,lunch or dinner was equally effective in controlling plasma glucose level, and the HbA1c was ( 6.70 ± 0.29 ) %, ( 6.80 ±0.32 ) %, (6.90 ± 0.21 ) % separately. The

  10. Phototoxicity to sulphonamide-derived oral antidiabetics and diuretics: comparative in-vitro and in-vivo investigations

    Science.gov (United States)

    Selvaag, Edgar; Anholt, Helle; Moan, Johan; Thune, Per

    1997-12-01

    Seven oral antidiabetics (chlorpropamide, glibenclamide, glipizide, gliquidone, glymidine, tolazamide, and tolbutamide), and 14 diuretics (bemetizide, bendroflumethiazide, benzylhydrochlorothiazide, bumetanide, butizide, chlortalidone, furosemide, hydrochlorothiazide, hydroflumethiazide, indapamide, piretanide, polythiazide, trichlormethiazide, and xipamide) were investigated for potential phototoxicity in vitro using a cell culture model and in vivo in hairless mice. After exposure to broad band UVA, the majority of the substances tested in vitro yielded phototoxic action leading to loss of culture forming ability. In vivo, all tested substances induced edema or ulceration, and lead to a significant increase in skin fold thickness of the mouse skin. In all a number of substances not described to induce clinical photosensitivity nor phototoxicity in vitro or in vivo were detected in our testing. In determining potential photosensitizers, it seems important to utilize different test methods, as not all substances will exhibit action in a given assay.

  11. The Antidiabetic Drug Metformin Stimulates Glycolytic Lactate Production in Cultured Primary Rat Astrocytes.

    Science.gov (United States)

    Westhaus, Adrian; Blumrich, Eva Maria; Dringen, Ralf

    2017-01-01

    Metformin is the most frequently used drug for the treatment of type 2 diabetes in humans. However, only little is known about effects of metformin on brain metabolism. To investigate potential metabolic consequences of an exposure of brain cells to metformin, we incubated rat astrocyte-rich primary cultures with this compound. Metformin in concentrations of up to 30 mM did not acutely compromise the viability of astrocytes, but caused a time- and concentration-dependent increase in cellular glucose consumption and lactate production. For acute incubations in the hour range, the presence of 10 mM metformin doubled the glycolytic flux, while already 1 mM metformin doubled glycolytic flux during incubation for 24 h. In addition to metformin, also other guanidino compounds increased astrocytic lactate production. After 4 h of incubation, half-maximal stimulation of glycolysis was observed for metformin, guanidine and phenformin at concentrations of around 3 mM, 3 mM and 30 µM, respectively. The acute stimulation of glycolytic lactate production by metformin was persistent after removal of extracellular metformin and was also observed, if glucose was absent from the incubation medium or replaced by other hexoses. The metformin-induced stimulation of glycolytic flux was not prevented by compound C, an inhibitor of AMP-dependent protein kinase, nor was it additive to the stimulation of glycolytic flux caused by respiratory chain inhibitors. These data demonstrate that the antidiabetic drug metformin has the potential to strongly activate glycolytic lactate production in brain astrocytes.

  12. Development of PPAR-agonist GW0742 as antidiabetic drug: study in animals

    Directory of Open Access Journals (Sweden)

    Niu HS

    2015-10-01

    increase of insulin sensitivity due to GW0742 was observed in these diabetic rats. Moreover, GW0742 reduced the hyperglycemia in T1DM rats lacking insulin. Western blotting analysis indicated that GW0742 reversed the decrease in GLUT4 and markedly reduced the increased PEPCK in liver.Conclusion: The data showed that GW0742 has the ability to improve glucose homeostasis in diabetic rats through activation of PPAR-δ. Therefore, PPAR-δ is a good target for the development of antidiabetic drugs in the future.Keywords: insulin resistance, fructose-rich chow, HOMA-IR, streptozotocin, insulinotropic action, rats

  13. Glycaemic control in patients with type 2 diabetes treated with oral antidiabetic drugs in urban areas of China%中国城市地区口服降糖药治疗的2型糖尿病患者血糖控制达标现状

    Institute of Scientific and Technical Information of China (English)

    陆菊明; 柳洁; 单忠艳; 杨玉芝; 胡仁明; 朱大龙; 杨立勇; 陈丽; 赵志刚; 李启富; 田浩明; 纪立农; 姬秋和; 刘静; 葛家璞; 时立新; 徐焱成; 郭晓蕙; 杨文英; 翁建平; 贾伟平; 邹大进; 周智广; 于德民

    2012-01-01

    目的 了解中国城市地区口服降糖药治疗的2型糖尿病(T2DM)患者的口服药治疗模式、血糖控制达标率及相关因素.方法 2010年7月至9月在全国30个省级行政区81个城市的414家医院,入选目前接受单纯口服降糖药治疗的门诊T2DM患者,收集患者的一般资料、糖尿病病史、实验室检查结果及治疗方案,以了解中国城市地区口服降糖药治疗的T2DM患者的口服药治疗模式、血糖控制达标率及相关因素.血糖达标的相关性分析采用逻辑回归模型分析.结果 共纳入97 315例T2DM患者,平均年龄(59±11)岁,病程(5±4)年,糖化血红蛋白(HbA1c)为7.7%±1.6%,HbA1c< 7.0%者34 154例(35.1%),HbA1c<6.5%者17 380例(17.9%).调查患者中12 748例(13.1%)合并有至少1种大血管病变,14 694例(15.1%)合并有至少1种微血管病变,合并有大或微血管并发症的患者血糖达标率分别为27.3%和25.2%,均低于未合并血管并发症组的36.3%和36.9%.口服药治疗方案中,双药(51.3%)、单药(34.5%)治疗较为常见,在单药、双药、3种药物和4种及以上药物联合治疗患者中,血糖达标率分别为40.6%、33.7%、27.0%和24.5%;单药治疗中,应用较多的为双胍类(30.8%)、磺脲类(24.6%)和格列奈类(21.1%);联合治疗中双胍类联合磺脲类者为23.7%,双胍类联合格列奈类者为13.6%.回归分析显示男性、糖尿病病程、口服药物种类数、体质指数、大血管病变、微血管病变与HbA1c达标率均呈显著负相关(OR=1.025、0.855、0.868、0.852、0.789、0.698,均P<0.01).结论 在中国应用口服药的T2DM患者中血糖控制达标率低,应进一步加强糖尿病管理,及时改变治疗方案,有效改善患者血糖控制状况.%Objective To investigate glycemic control,treatment regimen and other relevant characteristics in patients with type 2 diabetes mellitus( T2DM ) treated with oral antidiabetic drugs (OADs

  14. Comparison of anti-diabetic drug prescribing in children and adolescents in seven European countries

    NARCIS (Netherlands)

    Neubert, Antje; Hsia, Yingfen; de Jong-van den Berg, Lolkje T. W.; Janhsen, Katrin; Glaeske, Gerd; Furu, Kari; Kieler, Helle; Norgaard, Mette; Clavenna, Antonio; Wong, Ian C. K.

    2011-01-01

    AIMS The aim of this study was to compare the prevalence of diabetes in children across seven European countries, when using prescribing of anti-diabetics as a proxy for diabetes. A secondary aim was to assess the potential for collaboration between countries using different databases in diabetes re

  15. Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Ya-Yun [Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Tseng, Yu-Ting [Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Lo, Yi-Ching, E-mail: yichlo@kmu.edu.tw [Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China)

    2013-11-01

    Reactive oxygen intermediates production and apoptotic damage induced by high glucose are major causes of neuronal damage in diabetic neuropathy. Berberine (BBR), a natural antidiabetes drug with PI3K-activating activity, holds promise for diabetes because of its dual antioxidant and anti-apoptotic activities. We have previously reported that BBR attenuated H{sub 2}O{sub 2} neurotoxicity via activating the PI3K/Akt/Nrf2-dependent pathway. In this study, we further explored the novel protective mechanism of BBR on high glucose-induced apoptotic death and neurite damage of SH-SY5Y cells. Results indicated BBR (0.1–10 nM) significantly attenuated reactive oxygen species (ROS) production, nucleus condensation, and apoptotic death in high glucose-treated cells. However, AG1024, an inhibitor of insulin growth factor-1 (IGF-1) receptor, significantly abolished BBR protection against high glucose-induced neuronal death. BBR also increased Bcl-2 expression and decreased cytochrome c release. High glucose down-regulated IGF-1 receptor and phosphorylation of Akt and GSK-3β, the effects of which were attenuated by BBR treatment. BBR also activated nuclear erythroid 2-related factor 2 (Nrf2), the key antioxidative transcription factor, which is accompanied with up-regulation of hemeoxygenase-1 (HO-1). Furthermore, BBR markedly enhanced nerve growth factor (NGF) expression and promoted neurite outgrowth in high glucose-treated cells. To further determine the role of the Nrf2 in BBR neuroprotection, RNA interference directed against Nrf2 was used. Results indicated Nrf2 siRNA abolished BBR-induced HO-1, NGF, neurite outgrowth and ROS decrease. In conclusion, BBR attenuated high glucose-induced neurotoxicity, and we are the first to reveal this novel mechanism of BBR as an Nrf2 activator against glucose neurotoxicity, providing another potential therapeutic use of BBR on the treatment of diabetic complications. - Highlights: • BBR attenuates high glucose-induced ROS

  16. The Antidiabetics Market: Tendencies and Research Directions

    Directory of Open Access Journals (Sweden)

    Claudiu MOROGVAN

    2010-03-01

    Full Text Available Diabetes mellitus is a pathology with multiple and severe implications. Its prevalence has been continuously increasing during the last years, as well as the number of drugs introduced in its therapy. The value of the antidiabetics global market was evaluated at over 18 billion USD in 2005. The following five international producers hold the biggest share: NovoNordisk, Takeda, Sanofi-Aventis, GlaxoSmithkline and Eli Lilly. The two bestselling drugs in the USA in 2008 were Actos and Lantus, two products of latest generation, which, however, seems to be a global tendency. As far as the OAD (Oral Antidiabetic Drug category is concerned, the products to be prescribed in the following years will be those of latest generation, such as thiazolidinedione, GLP-1 analogues, DPP-4 inhibitors, as well as their fixed combinations with metformine. Rapid or slow acting Insulin analogues and their combinations with isophane insulins replace the classic insulins which seem to be outdated.

  17. 2010-2012年我院抗糖尿病药物应用分析%Use of anti-diabetic drugs of 2010-2012 in our hospital

    Institute of Scientific and Technical Information of China (English)

    陈娟娟; 杨世民; 薛京会

    2013-01-01

    Objective: To analyze use of anti-diabetic drugs in our hospital from 2010 through 2012 in order to provide some references for guiding and managing clinical use of anti-diabetic drugs. Methods: We analyzed consumption sum, defined daily dose(DDD), DDDs ,DDC and constituent ratio for anti-diabetic drugs use. Results: The sales amount of anti-diabetic drugs was increasing steadily. The top 3 DDDs were insulin glargine injection, repaglinide tablets and isophane protamine biosynthetic human insulin injection(pre-mixed 30R). The top 3 DDC were epalrestat tablets,insulin glargine injection and mixed protamine zinc recombinant human insulin lispro injection(25R). Conclusion: The use of anti-diabetic drugs was most rational in our hospital from 2010 to 2012. Non-sulfonylureas insulin secretagogues were often used in the clinic. The new , expensive oral drug and insulin preparations wil occupy a larger market, and we should pay close attention to this in clinic.%目的:分析我院2010-2012年抗糖尿病药物的应用情况,为其合理用药提供依据。方法:对我院2010-2012年抗糖尿病药物的使用数据用Excel2003软件进行销售金额、用药频度(DDDs)、构成比、日均费用(DDC)等统计分析。结果:我院抗糖尿病药物的用药金额逐年稳定上升,DDDs排在前3位的为甘精胰岛素、瑞格列奈、精蛋白生物合成人胰岛素(预混30R);DDC排名前3位的为依帕司他、甘精胰岛素、精蛋白锌重组赖脯胰岛素混合注射液(25R)。结论:我院2010-2012年抗糖尿病药物的使用状况较为合理,非磺脲类促胰岛素分泌剂的选用倾向较大,口服新贵药和胰岛素制剂将会占据更大份额,临床应引起足够重视。

  18. A drug utilization and pharmacoeconomic study of anti-diabetic drugs prescribed to type 2 diabetes mellitus patients visiting the medicine out-patient department of a tertiary care hospital of north India

    Directory of Open Access Journals (Sweden)

    Amandeep Singh

    2016-08-01

    Conclusions: Metformin was the most common OAD agent and insulin aspart was the most common injectable anti-diabetic drug prescribed in patients with T2DM. The newer anti-diabetic drugs sitagliptin and newer insulin analogues were also prescribed to a great extent. Overall, the prescribing trend was rational to a great extent and had improved since the earlier study in the same institute. The most cost-effective anti-diabetic therapy was combination therapy of glipizide and metformin. The cost of diabetes management is high, especially for insulin therapy. [Int J Basic Clin Pharmacol 2016; 5(4.000: 1220-1227

  19. Patterns and obstacles to oral antidiabetic medications adherence among type 2 diabetics in Ismailia, Egypt: a cross section study

    OpenAIRE

    Heissam, Khaled; Abuamer, Zeinab; El-Dahshan, Nahed

    2015-01-01

    Introduction Diabetes is a costly and increasingly common chronic disease. Effective management of diabetes to achieve glycemic control improves patient quality of life. Adherence rates to drug regimens in patients with type 2 diabetes are relatively low and vary widely between populations. There are many factors that could affect patient adherence to drug therapy. The aim of the present study was assessing patterns and obstacles to adherence of type 2 diabetic patients to their oral hypoglyc...

  20. Treating Diet-Induced Diabetes and Obesity with Human Embryonic Stem Cell-Derived Pancreatic Progenitor Cells and Antidiabetic Drugs

    Directory of Open Access Journals (Sweden)

    Jennifer E. Bruin

    2015-04-01

    Full Text Available Human embryonic stem cell (hESC-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported. An immunodeficient model of type 2 diabetes was generated by high-fat diet (HFD feeding in SCID-beige mice. Exposure to HFDs did not impact the maturation of macroencapsulated pancreatic progenitor cells into glucose-responsive insulin-secreting cells following transplantation, and the cell therapy improved glucose tolerance in HFD-fed transplant recipients after 24 weeks. However, since diet-induced hyperglycemia and obesity were not fully ameliorated by transplantation alone, a second cohort of HFD-fed mice was treated with pancreatic progenitor cells combined with one of three antidiabetic drugs. All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks. Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs.

  1. Nutrient-deprivation autophagy factor-1 (NAF-1: biochemical properties of a novel cellular target for anti-diabetic drugs.

    Directory of Open Access Journals (Sweden)

    Sagi Tamir

    Full Text Available Nutrient-deprivation autophagy factor-1 (NAF-1 (synonyms: Cisd2, Eris, Miner1, and Noxp70 is a [2Fe-2S] cluster protein immune-detected both in endoplasmic reticulum (ER and mitochondrial outer membrane. It was implicated in human pathology (Wolfram Syndrome 2 and in BCL-2 mediated antagonization of Beclin 1-dependent autophagy and depression of ER calcium stores. To gain insights about NAF-1 functions, we investigated the biochemical properties of its 2Fe-2S cluster and sensitivity of those properties to small molecules. The structure of the soluble domain of NAF-1 shows that it forms a homodimer with each protomer containing a [2Fe-2S] cluster bound by 3 Cys and one His. NAF-1 has shown the unusual abilities to transfer its 2Fe-2S cluster to an apo-acceptor protein (followed in vitro by spectrophotometry and by native PAGE electrophoresis and to transfer iron to intact mitochondria in cell models (monitored by fluorescence imaging with iron fluorescent sensors targeted to mitochondria. Importantly, the drug pioglitazone abrogates NAF-1's ability to transfer the cluster to acceptor proteins and iron to mitochondria. Similar effects were found for the anti-diabetes and longevity-promoting antioxidant resveratrol. These results reveal NAF-1 as a previously unidentified cell target of anti-diabetes thiazolidinedione drugs like pioglitazone and of the natural product resveratrol, both of which interact with the protein and stabilize its labile [2Fe-2S] cluster.

  2. PROSPECTS FOR DEVELOPMENT OF ANTIDIABETIC POLYPHENOL-BASED DRUGS: MECHANISMS OF HYPOGLYCEMIC ACTION AND PHARMACOKINETICS

    Directory of Open Access Journals (Sweden)

    Ruban E. A.

    2015-12-01

    Full Text Available Introduction. Diabetes mellitus is one of the most serious chronic diseases and considered to be non-infectious epidemic worldwide. Persistent hyperglycemia is a major hallmark of diabetes and risk factor for the development of its complications. Therefore, the main therapeutic goal in the treatment of diabetes is to reduce the elevated blood glucose level. Unfortunately, management of diabetes without any side effects is still a challenge to the modern medicine and pharmacy. Among potential alternatives to synthetic antidiabetic drugs plant polyphenols are very promising. However, polyphenol efficiency in diabetes is determined by their chemical structure and hence the affinity to a certain molecular targets in body tissues. Moreover, the bioavailability and other pharmacokinetic parameters of different individual substances may also vary significantly. In this context the present paper is devoted to the analysis of the available data on the hypoglycemic mechanisms and pharmacokinetics of various individual polyphenolic compounds in order to provide the necessary biopharmaceutical requirements in the development of a new blood glucose-lowering drug. Materials and methods. A systematic literature search of Pubmed, EMBASE and other databases with no language restrictions was performed until to the end of August 2015. The following terms were used: polyphenols, diabetes mellitus, hypoglycemic action, pharmacokinetics and bioavailability of polyphenols. Results and discussion. According to available experimental data various polyphenols may influence carbohydrate metabolism at many levels. The mechanisms by which plant polyphenols exert their hypoglycemic action are mediated primarily by their ability to directly bind to target proteins (or peptides and include inhibition of carbohydrate digestion and glucose absorption in the intestine, stimulation of insulin secretion from the pancreatic β-cells, modulation of glucose release from the liver

  3. Drug: D00594 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 675 452.5857 D00594.gif Antidiabetic [oral hypoglycemic agent] [DS:H00409] Same as: C07670 Therapeutic categ...Enzyme: CYP2C8 [HSA:1558], CYP3A4 [HSA:1576] Transporter: SLCO1B1 [HSA:10599] map07051 Antidiabetics Therape...utic category of drugs in Japan [BR:br08301] 3 Agents affecting metabolism 39 Other agents affecting metabolism 396 Antidiabetic...ation [BR:br08302] Blood Glucose Regulators Antidiabetic Agents Repaglinide D00594 Repaglinide (JAN/USP/INN)

  4. Development and validation of HPLC-UV-MS method for the control of four anti-diabetic drugs in suspected counterfeit products.

    Science.gov (United States)

    Dai, Xiu-mei; An, Ning; Wu, Jian-min; Li, Hui-yi; Zhang, Qi-ming

    2010-03-01

    An HPLC-UV method has been developed for the determination of valibose, miglitol, voglibose and acarbose, the four anti-diabetic drugs. The separation was accomplished successfully by using reversed phase chromatography (Prevail carbohydrate column, 250 mm x 4.6 mm, 5 microm) with a gradient acetonitrile-phosphate buffer solution (pH 8.0) at a wavelength of 210 nm. Furthermore, the method of a high-performance liquid chromatography coupled with ESI-MS in positive ionization mode has been established. These two methods were successfully applied to the assay and qualitative detection of four alpha-glucosidase inhibitors in the potential counterfeit anti-diabetic drugs.

  5. Glycemic control and antidiabetic drugs in type 2 diabetes mellitus patients with renal complications

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    Huri HZ

    2015-08-01

    Full Text Available Hasniza Zaman Huri,1,2 Lay Peng Lim,1 Soo Kun Lim3 1Department of Pharmacy, Faculty of Medicine, University of Malaya, 2Clinical Investigation Centre, University Malaya Medical Centre, 3Renal Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Background: Good glycemic control can delay the progression of kidney diseases in type 2 diabetes mellitus (T2DM patients with renal complications. To date, the association between antidiabetic agents and glycemic control in this specific patient population is not well established.Purpose: This study aimed to identify antidiabetic regimens as well as other factors that associated with glycemic control in T2DM patients with different stages of chronic kidney disease (CKD.Patients and methods: This retrospective, cross-sectional study involved 242 T2DM inpatients and outpatients with renal complications from January 2009 to March 2014 and was conducted in a tertiary teaching hospital in Malaysia. Glycated hemoglobin (A1C was used as main parameter to assess patients’ glycemic status. Patients were classified to have good (A1C <7% or poor glycemic control (A1C ≥7% based on the recommendations of the American Diabetes Association.Results: Majority of the patients presented with CKD stage 4 (43.4%. Approximately 55.4% of patients were categorized to have poor glycemic control. Insulin (57.9% was the most commonly prescribed antidiabetic medication, followed by sulfonylureas (43%. Of all antidiabetic regimens, sulfonylureas monotherapy (P<0.001, insulin therapy (P=0.005, and combination of biguanides with insulin (P=0.038 were found to be significantly associated with glycemic control. Other factors including duration of T2DM (P=0.004, comorbidities such as anemia (P=0.024 and retinopathy (P=0.033, concurrent medications such as erythropoietin therapy (P=0.047, a-blockers (P=0.033, and antigouts (P=0.003 were also correlated with A1C.Conclusion: Identification of

  6. Zinc oxide nanoparticles and a standard antidiabetic drug restore the function and structure of beta cells in Type-2 diabetes.

    Science.gov (United States)

    El-Gharbawy, Rehab Mohmed; Emara, Ashraf Mahmoud; Abu-Risha, Sally El-Sayed

    2016-12-01

    The aim of this study was to use Zinc oxide nanoparticles and a standard antidiabetic drug to restore the function and structure of beta cells in a rat model of Type-2 diabetes and compare the effects of a DPP-IV inhibitor with or without zinc oxide nanoparticles (ZnONPs) using a model of type 2 diabetes (rats fed a high fat diet that was treated with a low dose of streptozotocin). Ninety male Wistar rats were randomly divided into three groups 10days after the induction of diabetes: group I: non-diabetic animals that received only the chow diet plus 2ml of 0.5% carboxymethyl cellulose sodium; group II: diabetic animals that received only the chow diet plus 2ml of 0.5% carboxymethyl cellulose sodium; group III: diabetic animals were subdivided into 7 equal subgroups; one subgroup was administered Vildagliptin (10mg/kg/day p.o.); three subgroups were administered ZnONPs at doses of 1, 3 and 10mg/kg/day p.o.; and three subgroups were administered ZnONPs in different doses plus Vildagliptin for seven weeks. The DPP-IV inhibitor (Vildagliptin) and ZnONPs alone or in combination significantly decreased microRNA-103 and microRNA-143 expression compared to the diabetic group, indicating antidiabetic effects. ZnONPs improved many of the indices of diabetic dysfunction (glucose tolerance, weight loss, insulin levels, fructosamine levels, pancreatic SOD activity, and pancreas histology), but the addition of the DPP-IV further improved these indices. ZnONPs alone resulted in significant antidiabetic effects, whereas the addition of Vildagliptin resulted in a synergistic effect on the therapy of diabetes.

  7. An Oral Contraceptive Drug Interaction Study

    Science.gov (United States)

    Bradstreet, Thomas E.; Panebianco, Deborah L.

    2004-01-01

    This article focuses on a two treatment, two period, two treatment sequence crossover drug interaction study of a new drug and a standard oral contraceptive therapy. Both normal theory and distribution-free statistical analyses are provided along with a notable amount of graphical insight into the dataset. For one of the variables, the decision on…

  8. An Oral Contraceptive Drug Interaction Study

    Science.gov (United States)

    Bradstreet, Thomas E.; Panebianco, Deborah L.

    2004-01-01

    This article focuses on a two treatment, two period, two treatment sequence crossover drug interaction study of a new drug and a standard oral contraceptive therapy. Both normal theory and distribution-free statistical analyses are provided along with a notable amount of graphical insight into the dataset. For one of the variables, the decision on…

  9. Microencapsulation as a novel delivery method for the potential antidiabetic drug, Probucol

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    Mooranian A

    2014-09-01

    Full Text Available Armin Mooranian,1 Rebecca Negrulj,1 Nigel Chen-Tan,2 Hesham S Al-Sallami,3 Zhongxiang Fang,4 TK Mukkur,5 Momir Mikov,6,7 Svetlana Golocorbin-Kon,6,7 Marc Fakhoury,8 Gerald F Watts,9 Vance Matthews,10 Frank Arfuso,5 Hani Al-Salami1 1Biotechnology and Drug Development Research Laboratory School of Pharmacy, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, Western Australia, Australia; 2Faculty of Science and Engineering, Curtin University, Perth, Western Australia, Australia; 3School of Pharmacy, University of Otago, Dunedin, New Zealand; 4School of Public Health, Curtin University, Perth, Western Australia, Australia; 5Curtin Health Innovation Research Institute, Biosciences Research Precinct, School of Biomedical Science, Curtin University, Perth, Western Australia, Australia; 6Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Serbia; 7Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Serbia; 8Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada; 9School of Medicine and Pharmacology, Royal Perth Hospital, University of Western Australia; 10Laboratory for Metabolic Dysfunction, UWA Centre for Medical Research, Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia Introduction: In previous studies, we successfully designed complex multicompartmental microcapsules as a platform for the oral targeted delivery of lipophilic drugs in type 2 diabetes (T2D. Probucol (PB is an antihyperlipidemic and antioxidant drug with the potential to show benefits in T2D. We aimed to create a novel microencapsulated formulation of PB and to examine the shape, size, and chemical, thermal, and rheological properties of these microcapsules in vitro. Method: Microencapsulation was carried out using the Büchi-based microencapsulating system developed in our laboratory. Using the polymer, sodium

  10. Synthesis, spectroscopic, structural and thermal characterizations of vanadyl(IV) adenine complex prospective as antidiabetic drug agent

    Science.gov (United States)

    El-Megharbel, Samy M.; Hamza, Reham Z.; Refat, Moamen S.

    2015-01-01

    The vanadyl(IV) adenine complex; [VO(Adn)2]ṡSO4; was synthesized and characterized. The molar conductivity of this complex was measured in DMSO solution that showed an electrolyte nature. Spectroscopic investigation of the green solid complex studied here indicate that the adenine acts as a bidentate ligand, coordinated to vanadyl(IV) ions through the nitrogen atoms N7 and nitrogen atom of amino group. Thus, from the results presented the vanadyl(IV) complex has square pyramid geometry. Further characterizations using thermal analyses and scanning electron techniques was useful. The aim of this paper was to introduce a new drug model for the diabetic complications by synthesized a novel mononuclear vanadyl(IV) adenine complex to mimic insulin action and reducing blood sugar level. The antidiabetic ability of this complex was investigated in STZ-induced diabetic mice. The results suggested that VO(IV)/adenine complex has antidiabetic activity, it improved the lipid profile, it improved liver and kidney functions, also it ameliorated insulin hormone and blood glucose levels. The vanadyl(IV) complex possesses an antioxidant activity and this was clear through studying SOD, CAT, MDA, GSH and methionine synthase. The current results support the therapeutic potentiality of vanadyl(IV)/adenine complex for the management and treatment of diabetes.

  11. [Clinical pharmacology of two new oral antidiabetics of the sulfonamide type (author's transl)].

    Science.gov (United States)

    Haupt, E; Küllmer, K A; Schöffling, K

    1977-07-15

    Pharmacodynamic studies were performed with two new blood glucose lowering sulfonamides of high potency: gliquidone and gliflumide. The aim was to obtain equipotent doses on the basis of a maximum 30% blood glucose decrease in healthy normals (Ed 30) in order to compare the new compounds with the well known effects of tolbutamide and glibenclamide. Our investigations demonstrated a dose dependent blood glucose decrease with each sulfonylurea corresponding with the insulin levels after intravenous application. Gliquidone revealed a "tolbutamide-typed" dynamic both on insulin secretion and on blood glucose decrease whereas gliflumide showed a "glibenclamide-typed" reaction. The delayed and more prolonged insulin decrease, well known for glibenclamide, was even more distinct following gliflumide. Differences of insulin secretion after sulfonulureas can be observed only under intravenous conditions. Following oral application an only small increase of insulin can be noted when measured in peripheral blood.

  12. Re-Training of Type 2 Diabetic Patients for Better Adherence to Diabetes Care Plan in Oral Anti-Diabetics and Plus Insulin Treatment Groups

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    Soner Cander

    2015-06-01

    Full Text Available Purpose: This prospective observational single-centre study was designed to evaluate the effect of patient re-training for better adherence to regular self-monitoring of blood glucose (SMBG, standard diabetic diet and exercise program in ambulatory patients with type 2 diabetes mellitus (T2DM receiving oral anti-diabetic (OAD and OAD plus insulin treatments. Material and Method: In this study, we enrolled a total of 61 patients with T2DM in whom ongoing therapy with OAD (n=34 and OAD+insulin (n=27 failed to achieve adequate glycemic control. The patients were educated for lifestyle behavior, adherence to diet and exercise therapy, close monitoring with SMBG without change in their ongoing drugs and dosing. Changes in glycemic parameters, serum lipids and anthropometrics at the end of 3rd month were compared between the treatment groups. Results: During the course of the study, a significant decrease in the body weight and fat were observed in OAD (p<0.001 and p=0.002 and OAD+insulin groups (p=0.044 and p=0.008, respectively. A significant decrease in the HbA1c % (6.1%; 8.2% to 7.6% was observed in the overall population (p<0.001 as well as in OAD (p=0.011 and OAD+insulin (p=0.001 groups. A significant decrease was noted in the post-prandial capillary blood glucose levels in only OAD+insulin group. Discussion: Re-training approach with close follow-up and frequent SMBG seems to be important factors for the maintenance of achieved glycemic control. In our study, the effect of diabetes education on postprandial capillary blood glucose levels was more pronounced in OAD+insulin group. Turk Jem 2015; 19: 49-54

  13. Evaluation of the Prevalence of Chronic Kidney Disease and Rates of Oral Antidiabetic Prescribing in Accordance with Guidelines and Manufacturer Recommendations in Type 2 Diabetic Patients within a Long-Term Care Setting

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    Ning Wu

    2014-01-01

    Full Text Available This retrospective study assessed the prevalence of moderate to severe chronic kidney disease (CKD among nursing home (NH residents with type 2 diabetes. The pattern of oral antidiabetic drug (OAD use and their concordance with the National Kidney Foundation (NKF guideline and prescribing information (PI was also assessed. About half (47% of diabetic residents had moderate to severe CKD. A little over a quarter of the 186 residents using OADs received at least one NKF-discordant OAD prescription. Metformin was the most commonly misused OAD. PI nonconcordance was observed in 58.6% of residents and was highest in glipizide and metformin users. With the high prevalence of moderate to severe CKD in NH residents with diabetes, physicians should consider residents’ renal function when choosing treatment plans and review treatments regularly to check compliance with the NKF guidelines or PIs.

  14. The antidiabetic drug ciglitazone induces high grade bladder cancer cells apoptosis through the up-regulation of TRAIL.

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    Marie-Laure Plissonnier

    Full Text Available BACKGROUND: Ciglitazone belongs to the thiazolidinediones class of antidiabetic drug family and is a high-affinity ligand for the Peroxisome Proliferator-Activated Receptor γ (PPARγ. Apart from its antidiabetic activity, this molecule shows antineoplastic effectiveness in numerous cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: Using RT4 (derived from a well differentiated grade I papillary tumor and T24 (derived from an undifferentiated grade III carcinoma bladder cancer cells, we investigated the potential of ciglitazone to induce apoptotic cell death and characterized the molecular mechanisms involved. In RT4 cells, the drug induced G2/M cell cycle arrest characterized by an overexpression of p53, p21(waf1/CIP1 and p27(Kip1 in concomitance with a decrease of cyclin B1. On the contrary, in T24 cells, it triggered apoptosis via extrinsic and intrinsic pathways. Cell cycle arrest and induction of apoptosis occurred at high concentrations through PPARγ activation-independent pathways. We show that in vivo treatment of nude mice by ciglitazone inhibits high grade bladder cancer xenograft development. We identified a novel mechanism by which ciglitazone kills cancer cells. Ciglitazone up-regulated soluble and membrane-bound TRAIL and let TRAIL-resistant T24 cells to respond to TRAIL through caspase activation, death receptor signalling pathway and Bid cleavage. We provided evidence that TRAIL-induced apoptosis is partially driven by ciglitazone-mediated down-regulation of c-FLIP and survivin protein levels through a proteasome-dependent degradation mechanism. CONCLUSIONS/SIGNIFICANCE: Therefore, ciglitazone could be clinically relevant as chemopreventive or therapeutic agent for the treatment of TRAIL-refractory high grade urothelial cancers.

  15. A novel antidiabetic drug, fasiglifam/TAK-875, acts as an ago-allosteric modulator of FFAR1.

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    Chiori Yabuki

    Full Text Available Selective free fatty acid receptor 1 (FFAR1/GPR40 agonist fasiglifam (TAK-875, an antidiabetic drug under phase 3 development, potentiates insulin secretion in a glucose-dependent manner by activating FFAR1 expressed in pancreatic β cells. Although fasiglifam significantly improved glycemic control in type 2 diabetes patients with a minimum risk of hypoglycemia in a phase 2 study, the precise mechanisms of its potent pharmacological effects are not fully understood. Here we demonstrate that fasiglifam acts as an ago-allosteric modulator with a partial agonistic activity for FFAR1. In both Ca(2+ influx and insulin secretion assays using cell lines and mouse islets, fasiglifam showed positive cooperativity with the FFAR1 ligand γ-linolenic acid (γ-LA. Augmentation of glucose-induced insulin secretion by fasiglifam, γ-LA, or their combination was completely abolished in pancreatic islets of FFAR1-knockout mice. In diabetic rats, the insulinotropic effect of fasiglifam was suppressed by pharmacological reduction of plasma free fatty acid (FFA levels using a lipolysis inhibitor, suggesting that fasiglifam potentiates insulin release in conjunction with plasma FFAs in vivo. Point mutations of FFAR1 differentially affected Ca(2+ influx activities of fasiglifam and γ-LA, further indicating that these agonists may bind to distinct binding sites. Our results strongly suggest that fasiglifam is an ago-allosteric modulator of FFAR1 that exerts its effects by acting cooperatively with endogenous plasma FFAs in human patients as well as diabetic animals. These findings contribute to our understanding of fasiglifam as an attractive antidiabetic drug with a novel mechanism of action.

  16. 糖尿病治疗药物的再评价%Reappraisal of anti-diabetic drugs

    Institute of Scientific and Technical Information of China (English)

    刘静; 靳立英; 王云芳

    2011-01-01

    自从2007年糖尿病指南颁布3年以来,在糖尿病防治研究领域陆续完成了一系列重要研究,这些研究结论为糖尿病防治注入了大量新信息.在此背景下,对2007版糖尿病指南进行了再评价,并重新评估了常用糖尿病药物在糖尿病治疗治疗中的地位.文中结合《2010年中国2型糖尿病防治指南(讨论稿)》对各类糖尿病药物作用特点做一简要介绍.%In the 3 years since the publication of the 2007 guidelines of diabetes mellitus guidelines, research on diabetes mellitus has actively been pursued, and the results of new important studies (including several large-scale randomized trials) have been published. Some of these studies have reinforced the evidence on which the recommendations of the 2007 diabetes mellitus guidelines were based. Other studies have widened the information available in 2007, modifying some of the previous concepts. It is suggested that new evidence based on recommendations could be appropriated, especially in the aspects of anti-diabetic drugs. The aim of this review article was to address the renewed concepts of the clinical recommendations of anti-diabetic drugs based on the 2010 edition of diabetes mellitus guidelines.

  17. Pharmacogenomics of oral antiplatelet drugs.

    Science.gov (United States)

    Yasmina, Alfi; de Boer, Anthonius; Klungel, Olaf H; Deneer, Vera H M

    2014-03-01

    Pharmacogenomics has been implicated in the response variability of antiplatelet drugs in coronary artery disease (CAD), particularly for aspirin and clopidogrel. A large number of studies and several meta-analyses have been published on this topic, but until recently, there have been no clear conclusions and no definite guidelines on the clinical use of pharmacogenetic testing before prescribing antiplatelet drugs for CAD. In this review, the available evidence is summarized. The most consistent results are on clopidogrel, where CYP2C19 loss-of-function alleles are associated with stent thrombosis events. We recommend to genotype for CYP2C19 loss-of-function alleles in patients with CAD who are to undergo percutaneous coronary intervention and stenting, and to adjust the antiplatelet treatment based on the genotyping results.

  18. Progress of pharmacogenomic studies on anti-diabetic drugs%口服降糖药的药物基因组学研究进展

    Institute of Scientific and Technical Information of China (English)

    王婕; 贾伟平

    2009-01-01

    药物基因组学是研究基因组变异与药物疗效、安全性间关系的学科.本文主要介绍临床常用降糖药的药物基因组学研究进展.%Pharmacogenomics aims to identify the effects of genomie variants on drug efficacy and safety. This article summarized the progress of pharmacogenomic study on anti-diabetic drugs.

  19. Nuevas terapias en diabetes: más allá de la insulina inyectable y de los antidiabéticos orales New therapies for diabetes: beyond injectable insulin and oral antidiabetics

    Directory of Open Access Journals (Sweden)

    John Edwin Feliciano Alfonso

    2008-10-01

    Full Text Available Novos medicamentos para o tratamento do diabetes tipo 1 e tipo 2 foram incorporados à lista de fármacos tradicionais: antidiabéticos orais e insulinas injetáveis. Estas alternativas de tratamento têm novos mecanismos de ação que aproveitam as propriedades antidiabéticas de certos peptídeos como é o caso da amilina ou do peptídeo similar ao glucagon (GLP-1, cujos níveis são deficientes ou insuficientes no diabetes. Isto acontece pelos análogos da amilina ou do GLP-1, embora também possa ser obtido inibindo a enzima que degrada este último. Além disso, encontra-se disponível no mercado um novo sistema para administrar insulina de maneira não-invasiva por meio de inalação. Este artigo resume os resultados mais importantes e atualizados com relação ao mecanismo de ação, eficácia, efeitos adversos e indicações destes fármacos inovadores.New medicines for the therapy of the type 1 and type 2 diabetes have been incorporated in the list of traditional drugs: oral agents and injectable insulin. These treatment alternatives have a new mechanism of action that takes advantage of the antidiabetic properties of certain peptides such as amylin and glucagon like peptide-1 (GLP-1, whose levels are wanting or insufficient in diabetes. This is attained through amylin and GLP-1 analogues, although it can also be achieved by inhibiting the enzyme that degrades the latter. Furthermore, a new system to administer insulin in a noninvasive way through inhalation has become available in the market. This paper summarizes the most important and updated findings on the action mechanism, efficacy, adverse effects and indications of these innovative drugs.

  20. The Antidiabetic Drug Metformin Inhibits the Proliferation of Bladder Cancer Cells in Vitro and in Vivo

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    Tao Zhang

    2013-12-01

    Full Text Available Recent studies suggest that metformin, a widely used antidiabetic agent, may reduce cancer risk and improve prognosis of certain malignancies. However, the mechanisms for the anti-cancer effects of metformin remain uncertain. In this study, we investigated the effects of metformin on human bladder cancer cells and the underlying mechanisms. Metformin significantly inhibited the proliferation and colony formation of 5637 and T24 cells in vitro; specifically, metformin induced an apparent cell cycle arrest in G0/G1 phases, accompanied by a strong decrease of cyclin D1, cyclin-dependent kinase 4 (CDK4, E2F1 and an increase of p21waf-1. Further experiments revealed that metformin activated AMP-activated protein kinase (AMPK and suppressed mammalian target of rapamycin (mTOR, the central regulator of protein synthesis and cell growth. Moreover, daily treatment of metformin led to a substantial inhibition of tumor growth in a xenograft model with concomitant decrease in the expression of proliferating cell nuclear antigen (PCNA, cyclin D1 and p-mTOR. The in vitro and in vivo results demonstrate that metformin efficiently suppresses the proliferation of bladder cancer cells and suggest that metformin may be a potential therapeutic agent for the treatment of bladder cancer.

  1. Review: Ontogeny of oral drug absorption processes in children

    OpenAIRE

    Mooij, Miriam; Koning, De; Huijsman, Mark; de Wildt, Saskia

    2012-01-01

    textabstractA large proportion of prescribed drugs to children are administered orally. Age-related change in factors affecting oral absorption can have consequences for drug dosing. Areas covered: For each process affecting oral drug absorption, a systematic search has been performed using Medline to identify relevant articles (from inception till February 2012) in humans. This review presents the findings on age-related changes of the following processes affecting oral drug absorption: gast...

  2. Blood Pressure-Lowering Aspects of Lipid-Lowering and Anti-Diabetic Drugs

    Directory of Open Access Journals (Sweden)

    Peter M. Nilsson

    2010-12-01

    Full Text Available Several studies have shown that blood pressure can be lowered by the use of drugs that are not traditional antihypertensive drugs. This might be of clinical importance when many risk patients are treated by combination drug therapy in order to prevent cardiovascular disease by way of improving the cardiovascular risk factor profile.

  3. Review: Ontogeny of oral drug absorption processes in children

    NARCIS (Netherlands)

    M.G. Mooij (Miriam); B.A.E. Koning, de (Barbara); M.L. Huijsman (Mark); S.N. de Wildt (Saskia)

    2012-01-01

    textabstractA large proportion of prescribed drugs to children are administered orally. Age-related change in factors affecting oral absorption can have consequences for drug dosing. Areas covered: For each process affecting oral drug absorption, a systematic search has been performed using Medline

  4. Anti-diabetes drug pioglitazone ameliorates synaptic defects in AD transgenic mice by inhibiting cyclin-dependent kinase5 activity.

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    Jinan Chen

    Full Text Available Cyclin-dependent kinase 5 (Cdk5 is a serine/threonine kinase that is activated by the neuron specific activators p35/p39 and plays many important roles in neuronal development. However, aberrant activation of Cdk5 is believed to be associated with the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease (AD and Parkinson's disease (PD. Here in the present study, enhanced Cdk5 activity was observed in mouse models of AD; whereas soluble amyloid-β oligomers (Aβ, which contribute to synaptic failures during AD pathogenesis, induced Cdk5 hyperactivation in cultured hippocampal neurons. Inhibition of Cdk5 activity by pharmacological or genetic approaches reversed dendritic spine loss caused by soluble amyloid-β oligomers (Aβ treatment. Interestingly, we found that the anti-diabetes drug pioglitazone could inhibit Cdk5 activity by decreasing p35 protein level. More importantly, pioglitazone treatment corrected long-term potentiation (LTP deficit caused by Aβ exposure in cultured slices and pioglitazone administration rescued impaired LTP and spatial memory in AD mouse models. Taken together, our study describes an unanticipated role of pioglitazone in alleviating AD and reveals a potential therapeutic drug for AD curing.

  5. Marine algae as a prospective source for antidiabetic compounds - A brief review.

    Science.gov (United States)

    Unnikrishnan, S P; Jayasri, A M

    2016-12-29

    Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycaemia, which is attributed by several life threatening complications including atherosclerosis, nephropathy, and retinopathy. The current therapies available for the management of DM mainly include oral antidiabetic drugs and insulin injections. However, continuous use of synthetic drugs provides lower healing with many side effects. Therefore, there is an urge for safe and efficient antidiabetic drugs for the management of DM. In the continuing search for effective antidiabetic drugs, marine algae (seaweeds) remains as a promising source with potent bioactivity. It is anticipated that the isolation, characterization, and pharmacological study of unexplored marine algae can be useful in the discovery of novel antidiabetic compounds with high biomedical value. Among marine algae, brown and red algae are reported to exhibit antidiabetic activity. Majority of the investigations on algal derived compounds controls the blood glucose levels through the inhbition of carbohydrate hydroloyzing enzymes and protein tyrosine phosphatase 1B enzymes, insulin sensitization, glucose uptake effect and other protective effects against diabetic complications. Based on the above perspective this review provides; profiles for various marine algae posessing antidiabetic activity. This study also highlights the therapeutic potential of compounds isolated from marine algae for the effective management of diabetes and its associated complications.

  6. Connectivity maps for biosimilar drug discovery in venoms: the case of Gila monster venom and the anti-diabetes drug Byetta®.

    Science.gov (United States)

    Aramadhaka, Lavakumar Reddy; Prorock, Alyson; Dragulev, Bojan; Bao, Yongde; Fox, Jay W

    2013-07-01

    instances and negative correlation with 868 instances. Interestingly, the Gila monster venom and Byetta(®) both showed positive correlation with the anti-diabetic drugs troglitazone, of the thiazolidinedione class, and metformin, of the biguanide class, although Byetta(®) as a glucagon-like peptide-1 (GLP-1) agonist functions in a different manner than either of these two classes of anti-diabetic drugs. In summary, despite the fact that Gila monster venom contains a mixture of biologically active molecules, similarities in terms of perturbation of gene expression profiles on MCF7 cells were observed between the venom and the drug Byetta(®). Furthermore, using Connectivity Mapping the Gila monster venom was demonstrated to have nodes of positive correlation to several anti-diabetic drugs two of which were the same as observed with Byetta(®). Therefore, this study suggests that by using this approach novel drug activities heretofore unconsidered may be discovered in venoms using informatic tools and Connectivity Mapping. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Antidiabetic oils.

    Science.gov (United States)

    Berraaouan, Ali; Abid, Sanae; Bnouham, Mohamed

    2013-11-01

    Many studies have demonstrated evidence of the health benefits of natural products. Plant extracts have been tested on a variety of physiological disorders, including diabetes mellitus. Studies have tested aqueous extracts, plant fractions extracts, families of active of compounds, and specific active compounds. In this review, we describe the antidiabetic effects of vegetable oils. Information was collected from ScienceDirect and PubMed databases using the following key words: Diabetes mellitus, Oils, Vegetable oils, Type 1 diabetes, type 2 diabetes, antidiabetic effect, antihyperglycemic, antidiabetic oil. We have compiled approximately ten vegetable oils with including experimental studies that have demonstrated benefits on diabetes mellitus. There are soybean, argan, olive, palm, walnut, black cumin, safflower, Colocynth, Black seed, Rice bran, Cinnamom, and Rocket oils. For each vegetable oil, we investigated on the plant's traditional uses, their pharmacological activities and their antidiabetic effects. It seems that many vegetable oils are really interesting and can be used in the improvement of human health, particularly, to prevent or to treat diabetes mellitus complications.

  8. Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs

    NARCIS (Netherlands)

    R.W.F. van Leeuwen (Roelof); D.H.S. Brundel (D. H S); C. Neef (Cees); T. van Gelder (Teun); A.H.J. Mathijssen (Ron); D.M. Burger (David); F.G.A. Jansman (Frank)

    2013-01-01

    textabstractBackground: Potential drug-drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment.

  9. Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs

    NARCIS (Netherlands)

    van Leeuwen, R. W. F.; Brundel, D. H. S.; Neef, C.; van Gelder, T.; Mathijssen, R. H. J.; Burger, D. M.; Jansman, F. G. A.

    2013-01-01

    Background: Potential drug-drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment. Methods: A

  10. Effects of commonly used antidiabetic drugs on antioxidant enzymes and liver function test markers in type 2 diabetes mellitus subjects - pilot study.

    Science.gov (United States)

    Ghadge, A; Harke, S; Khadke, S; Diwan, A; Pankaj, M; Kulkarni, O; Ranjekar, P; Harsulkar, A; Kuvalekar, A A

    2015-09-01

    The present study analyzed the effects of antidiabetic drugs on antioxidant enzymes and liver function test (LFT) markers and their association with homeostatic model assessment of insulin resistance (HOMA-IR) in type 2 diabetic subjects. We assessed healthy and diabetic subjects (100 each). Diabetic subjects were divided based on treatment with only metformin, metformin in combination with other antidiabetic drugs and insulin in combination with other antidiabetic drugs. LFT markers, antioxidant status and HOMA-IR were assessed in the subjects. Superoxide dismutase activity was higher (plevels were higher in diabetic male subjects while urea (plevels were lower and SGPT (plevels were higher in diabetic female subjects. In male subjects consuming only metformin, a positive association between HOMA-IR and insulin (pantioxidant enzyme activities and liver function tests are dependent upon the gender and glycemic status of subjects while the variations in correlations of HOMA-IR with antioxidant enzymes, liver function tests and inflammatory markers are dependent on type of treatments. © Georg Thieme Verlag KG Stuttgart · New York.

  11. The anti-diabetic drug metformin reduces BACE1 protein level by interfering with the MID1 complex.

    Directory of Open Access Journals (Sweden)

    Moritz M Hettich

    Full Text Available Alzheimer's disease (AD, the most common form of dementia in the elderly, is characterized by two neuropathological hallmarks: senile plaques, which are composed of Aβ peptides, and neurofibrillary tangles, which are composed of hyperphosphorylated TAU protein. Diabetic patients with dysregulated insulin signalling are at increased risk of developing AD. Further, several animal models of diabetes show increased Aβ expression and hyperphosphorylated tau. As we have shown recently, the anti-diabetic drug metformin is capable of dephosphorylating tau at AD-relevant phospho-sites. Here, we investigated the effect of metformin on the main amyloidogenic enzyme BACE1 and, thus, on the production of Aβ peptides, the second pathological hallmark of AD. We find similar results in cultures of primary neurons, a human cell line model of AD and in vivo in mice. We show that treatment with metformin decreases BACE1 protein expression by interfering with an mRNA-protein complex that contains the ubiquitin ligase MID1, thereby reducing BACE1 activity. Together with our previous findings these results indicate that metformin may target both pathological hallmarks of AD and may be of therapeutic value for treating and/or preventing AD.

  12. Probiotic B420 and prebiotic polydextrose improve efficacy of antidiabetic drugs in mice

    National Research Council Canada - National Science Library

    Stenman, Lotta K; Waget, Aurélie; Garret, Céline; Briand, François; Burcelin, Rémy; Sulpice, Thierry; Lahtinen, Sampo

    2015-01-01

    Gut microbiota is now known to control glucose metabolism. Previous studies have shown that probiotics and prebiotics may improve glucose metabolism, but their effects have not been studied in combination with drug therapy...

  13. Pattern of antidiabetic drugs use in type-2 diabetic patients in a medicine outpatient clinic of a tertiary care teaching hospital

    Directory of Open Access Journals (Sweden)

    Bela Patel

    2013-08-01

    Full Text Available Background: Diabetes mellitus (DM is an important public health problem in developing countries. Drug utilisation study of antidiabetic agents is of paramount importance to promote rational drug use in diabetics and make available valuable information for the healthcare team. The aim of study was to investigate the drug utilization pattern in type-2 diabetic patients. Methods: A prospective, cross-sectional study was carried out in medicine outpatient clinic of tertiary care hospital, Ahmedabad for eight weeks. Patients with type-2 diabetes and on drug therapy for at least one month were included. Patients’ socio-demographic and clinical data were noted in a pre-designed proforma. Data was analysed by using SPSS version 20 and Excel 2007. Results: Total 114 patients were enrolled with mean (± standard deviation age and duration of diabetes of 56.8 ± 10.5 and 8.3 ± 9.4 years respectively. Male: Female ratio was 0.72:1. Mean fasting and postprandial blood glucose levels were 147.5 ± 73.1 and 215.6 ± 97.3 mg/dl respectively. Most common symptom was weakness/fatigue (77.2%. Hypertension (70.2% was most common co-morbid illness. Mean number of drugs prescribed were 7.8 ± 2.5. Total numbers of patients receiving more than five drugs were 89.5%. Most commonly used drug group was biguanides (87.7% followed by sulphonylureas (68.4%. Conclusion: Metformin (biguanide was the most utilized (87.7% antidiabetic drug for type-2 diabetes. This study revealed that the pattern of antidiabetic prescription was rational and largely compliant with NICE (National Institute for Health and Clinical Excellence guidelines. [Int J Basic Clin Pharmacol 2013; 2(4.000: 485-491

  14. Synthesis and Characterization of Process-Related Impurities of Antidiabetic Drug Linagliptin.

    Science.gov (United States)

    Huang, Yiwen; He, Xiaoqing; Wu, Taizhi; Zhang, Fuli

    2016-08-09

    Linagliptin, a xanthine derivative, is a highly potent, selective, long-acting and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. During the process development of linagliptin, five new process-related impurities were detected by high performance liquid chromatography (HPLC). All these impurities were identified, synthesized, and subsequently characterized by their respective spectral data (MS, HRMS, ¹H-NMR, (13)C-NMR and IR) as described in this article. The identification of these impurities should be useful for quality control and the validation of the analytical method in the manufacture of linagliptin.

  15. Synthesis and Characterization of Process-Related Impurities of Antidiabetic Drug Linagliptin

    Directory of Open Access Journals (Sweden)

    Yiwen Huang

    2016-08-01

    Full Text Available Linagliptin, a xanthine derivative, is a highly potent, selective, long-acting and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. During the process development of linagliptin, five new process-related impurities were detected by high performance liquid chromatography (HPLC. All these impurities were identified, synthesized, and subsequently characterized by their respective spectral data (MS, HRMS, 1H-NMR, 13C-NMR and IR as described in this article. The identification of these impurities should be useful for quality control and the validation of the analytical method in the manufacture of linagliptin.

  16. Preclinical and clinical pharmacology of oral anticancer drugs

    NARCIS (Netherlands)

    Oostendorp, R.L.

    2009-01-01

    Nowadays, more than 25% of all anticancer drugs are developed as oral formulations. Oral administration of drugs has several advantages over intravenous (i.v.) administration. It will on average be more convenient for patients, because they can take oral medication themselves, there is no need for

  17. Preclinical and clinical pharmacology of oral anticancer drugs

    NARCIS (Netherlands)

    Oostendorp, R.L.

    2009-01-01

    Nowadays, more than 25% of all anticancer drugs are developed as oral formulations. Oral administration of drugs has several advantages over intravenous (i.v.) administration. It will on average be more convenient for patients, because they can take oral medication themselves, there is no need for f

  18. [Metformin - new data for an "old", but efficient, safe and reliable antidiabetic drug].

    Science.gov (United States)

    Winkler, Gábor

    2016-06-01

    Metformin is the basic drug of antihyperglycemic therapy in type 2 diabetes: according to actual therapeutic guidelines, it should be given in the absence of contraindications or intolerance during the whole course of the disease even after the initiation of insulin therapy. Recently more and more details have been explored regarding the molecular background of its effects, however, in parallel with the enormous growing knowledge, the number of questions still waiting to be answered has also grown. This review article deals with data already crystallized as well as with details not definitely cleared up. Genetic polymorphisms as well as potential drug interactions influencing the effects of metformin are also briefly summarized.

  19. Parametric time-to-onset (TTO) modelling of common ADRs in patients using antidiabetic drugs

    NARCIS (Netherlands)

    Scholl, Joep H.G.; Van De Ven, Peter M.; Van Puijenbroek, Eugène P.

    2015-01-01

    Background: Although the time-to-onset (TTO) is an important aspect in causality assessment of adverse drug reactions (ADRs), limited information about it is available in publicly available literature. Objectives: The aim of this study was to investigate whether the TTO of common ADRs of antidiabeti

  20. Thrice-daily biphasic insulin aspart 30 may be another therapeutic option for Chinese patients with type 2 diabetes inadequately controlled with oral antidiabetic agents

    Institute of Scientific and Technical Information of China (English)

    YANG Wen-ying; JI Qiu-he; ZHU Da-long; YANG Jin-kui; CHEN Lu-lu; LIU Zhi-min; YU De-min; YAN Li

    2009-01-01

    In subjects with type 2 diabetes inadequately controlled with oral antidiabetic agents (OADs), insulin therapy is usually started to improve glycaemic control after failure of diet, exercise and OADs.1 Although there is no standard way to introduce insulin treatment, premixed formulations are a popular option. They offer an alternative to basal-bolus therapy and provide basal and prandial coverage with a single injection. Indeed, Koivisto et al2 in 1999 reported that 39% of patients with type 2 diabetes worldwide used premixed insulin as part of their therapeutic regimen. The modem premixed insulins, such as biphasic insulin aspart 30 (BIAsp 30) are most frequently prescribed twice-daily (BID) in clinical Department of Endocrinology, China-Japan Friendship Hospital, Beijing 100029, China (Yang WY)

  1. Establishment of liver specific glucokinase gene knockout mice:a new animal model for screening anti-diabetic drugs

    Institute of Scientific and Technical Information of China (English)

    Ya-li ZHANG; Xiao-hong TAN; Mei-fang XIAO; Hui LI; Yi-qing Mao; Xiao YANG; Huan-ran TAN

    2004-01-01

    AIM: To characterize the liver-specific role of glucokinase in maintaining glucose homeostasis and to create an animal model for diabetes. METHODS: We performed hepatocyte-specific gene knockout of glucokinase in mice using Cre-loxP gene targeting strategy. First, two directly repeated loxP sequences were inserted to flank the exon 9 and exon 10 of glucokinase in genomic DNA. To achieve this, linearized targeting vector was electroporated into ES cells. Then G418- and Gancyclovir-double-resistant clones were picked and screened by PCR analysis and the positives identified by PCR were confirmed by Southern blot. A targeted clone was selected for microinjection into C57BL/6J blastocysts and implanted into pseudopregnant FVB recipient. Chimeric mice and their offspring were analyzed by Southern blot. Then by intercrossing the Alb-Cre transgenic mice with mice containing a conditional gk allele, we obtained mice with liver-specific glucokinase gene knockout. RESULTS: Among 161 double resistant clones 4 were positive to PCR and Southern blot and only one was used for further experiments. Eventually we generated the liver specific glucokinase knockout mice. These mice showed increased glucose level with age and at the age of 6 weeks fasting blood glucose level was significantly higher than control and they also displayed impaired glucose tolerance. CONCLUSION: Our studies indicate that hepatic glucokinase plays an important role in glucose homeostasis and its deficiencies contribute to the development of diabetes. The liver glucokinase knockout mouse is an ideal animal model for MODY2, and it also can be applied for screening anti-diabetic drugs.

  2. Berberine as a promising anti-diabetic nephropathy drug: An analysis of its effects and mechanisms.

    Science.gov (United States)

    Ni, Wei-Jian; Ding, Hai-Hua; Tang, Li-Qin

    2015-08-05

    Diabetic nephropathy is a progressive kidney disorder and is pathologically characterized by thickened glomerular and tubular basement membranes, accumulation of the extracellular matrix and increased mesangial hypertrophy. Growing evidence has suggested that diabetic nephropathy is induced by multiple factors, such as dyslipidemia, hyperglycemia, hemodynamic abnormalities and oxidative stress, based on genetic susceptibility. Berberine (BBR; [C20H18NO4](+)), an isoquinoline alkaloid, is the major active constituent of Rhizoma coptidis and Cortex phellodendri. Recent studies have demonstrated that berberine has various pharmacological activities, including lowering blood glucose, regulating blood lipids and reducing inflammation in addition to its antioxidant activity. These findings suggest that berberine has potential applications as a therapeutic drug for diabetic nephropathy, and has significant research value. However, the possible mechanisms have not been fully established. The purpose of this paper is to investigate the renoprotective mechanisms of berberine in diabetic nephropathy and highlight the importance of berberine as a potential therapeutic reagent for diabetic nephropathy treatment.

  3. Causative anti-diabetic drugs and the underlying clinicalfactors for hypoglycemia in patients with diabetes

    Institute of Scientific and Technical Information of China (English)

    Hidekatsu Yanai; Hiroki Adachi; Hisayuki Katsuyama; Sumie Moriyama; Hidetaka Hamasaki; Akahito Sako

    2015-01-01

    Recent clinical trials indicated that the intensiveglycemic control do not reduce cardiovascular diseasemortality among diabetic patients, challenging asignificance of the strict glycemic control in diabetesmanagement. Furthermore, retrospective analysis ofthe Action to Control Cardiovascular Risk in Diabetesstudy demonstrated a significant association betweenhypoglycemia and mortality. Here, we systematicallyreviewed the drug-induced hypoglycemia, and alsothe underlying clinical factors for hypoglycemiain patients with diabetes. The sulfonylurea use issignificantly associated with severe hypoglycemia inpatients with type 2 diabetes. The use of biguanide(approximately 45%-76%) and thiazolidinediones(approximately 15%-34%) are also highly associatedwith the development of severe hypoglycemia. Inpatients treated with insulin, the intensified insulintherapy is more frequently associated with severehypoglycemia than the conventional insulin therapy andcontinuous subcutaneous insulin infusion. Among theunderlying clinical factors for development of severehypoglycemia, low socioeconomic status, aging, longerduration of diabetes, high HbA1c and low body massindex, comorbidities are precipitating factors for severehypoglycemia. Poor cognitive and mental functions arealso associated with severe hypoglycemia.

  4. Efficacy of canagliflozin combined with antidiabetic drugs in treating type 2 diabetes mellitus: Meta-analysis of randomized control trials.

    Science.gov (United States)

    Meng, Qi; Shen, Yun; Liu, Dajin; Jiang, Fei

    2016-05-01

    Canagliflozin has been proposed as an effective treatment for type 2 diabetes. This meta-analysis of randomized control trials aimed to evaluate the effect of canagliflozin combined with other hypoglycemic drugs. We searched Medline, Embase, Cochrane Library, Google Scholar and ClinicalTrials.gov for randomized control trials comparing canagliflozin combined with conventional antidiabetic drugs vs placebo. Our main end-points were glycemic control and change in weight. We assessed pooled data by use of a random-effects model. Of 161 identified studies, six were eligible and were included in our analysis (n = 4670 participants). Compared with the placebo, mean changes in glycosylated hemoglobin were -0.60% (95% confidence interval -0.67 to -0.54%; I (2) = 0%) for canagliflozin 100 mg, and -0.76% (95% confidence interval -0.84 to -0.68%; I (2) = 20%) for canagliflozin 300 mg with bodyweight loss. Canagliflozin as an add-on drug to other antidiabetic drugs effectively lowers blood glucose without significant weight gain.

  5. Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide

    Science.gov (United States)

    Candeias, Emanuel Monteiro; Sebastião, Inês Carolina; Cardoso, Susana Maria; Correia, Sónia Catarina; Carvalho, Cristina Isabel; Plácido, Ana Isabel; Santos, Maria Sancha; Oliveira, Catarina Resende; Moreira, Paula Isabel; Duarte, Ana Isabel

    2015-01-01

    Long-acting glucagon-like peptide-1 (GLP-1) analogues marketed for type 2 diabetes (T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia. In this regard, it has also been suggested that stimulation of brain insulin signaling may have a protective role against cognitive deficits. As GLP-1 receptors (GLP-1R) are expressed throughout the central nervous system and GLP-1 may cross the blood-brain-barrier, an emerging hypothesis suggests that they may be promising therapeutic targets against brain dysfunctional insulin signaling-related pathologies. Importantly, GLP-1 actions depend not only on the direct effect mediated by its receptor activation, but also on the gut-brain axis involving an exchange of signals between both tissues via the vagal nerve, thereby regulating numerous physiological functions (e.g., energy homeostasis, glucose-dependent insulin secretion, as well as appetite and weight control). Amongst the incretin/GLP-1 mimetics class of anti-T2D drugs with an increasingly described neuroprotective potential, the already marketed liraglutide emerged as a GLP-1R agonist highly resistant to dipeptidyl peptidase-4 degradation (thereby having an increased half-life) and whose systemic GLP-1R activity is comparable to that of native GLP-1. Importantly, several preclinical studies showed anti-apoptotic, anti-inflammatory, anti-oxidant and neuroprotective effects of liraglutide against T2D, stroke and Alzheimer disease (AD), whereas several clinical trials, demonstrated some surprising benefits of liraglutide on weight loss

  6. 2型糖尿病从预混胰岛素转换为甘精胰岛素联合口服降糖药物治疗的观察性研究%Study of treatment switching from premixed insulin to glargine combined with oral antidiabetic drugs of patients with type 2 diabetic

    Institute of Scientific and Technical Information of China (English)

    杨艳; 李蓬秋; 包明晶; 刘丽梅; 张学军; 鲜杨; 吴冀川; 张磊; 朱显军

    2014-01-01

    目的 观察2型糖尿病患者从预混胰岛素转换为甘精胰岛素联合口服降糖药物(OADs)治疗的效果、安全性和患者的满意度.方法 采用自身前后对照研究,选择2型糖尿病患者,接受预混胰岛素治疗至少3个月,联合/或未联合OADs治疗,且糖化血红蛋白(HbA1c)≤10.0%的2型糖尿病患者43例,基于患者和医师的考虑,将预混胰岛素转换为甘精胰岛素联合OADs治疗,由医师根据血糖调整胰岛素和OADs的剂量,随访16周,目标空腹血糖≤5.6 mmol/L.结果 共36例患者完成全部随访观察,治疗16周后空腹血糖、餐后2h血糖、HbA1c均与治疗前相当(P均>0.05),而胰岛素用量明显减少[(23.8±6.0)、(9.6±4.0) U/d,t=13.59,P<0.01],体质量指数较治疗前明显下降[(24.4±2.9)、(23.8±2.8)kg/m2,t=3.25,P<0.05];随访期间36例入组患者中15例患者共发生低血糖30次,低血糖发生率41.7%(15/36),均无需他人帮助,少量进食后缓解,无重度低血糖发生,无患者因低血糖反应而退出本研究;36例患者转换前治疗总体满意率为36.1% (13/36),转换后为72.2%(26/36),转换后总体满意度明显高于转换前(x2=6.26,P<O.05).结论 HbA1c≤7.0%时将预混胰岛素转换为甘精胰岛素联合OADs治疗能有效控制血糖,且胰岛素用量及注射次数减少,患者体质量减轻,治疗满意度高.%Objective To evaluation the efficacy,safety and treatment satisfaction of glargine plus oral medications(OADs) switching from premixed insulin on patients with type 2 diabetic.Methods Forty-three patients with type 2 diabetes were enrolled into our study.All patients were treated with twice-daily premixed insulin therapy for at least 3 months with or without OADs and their glycosylated haemoglobin(HbA1c) were less than 10.0%.The aim of OADs treatment was FBG ≤ 5.6 mmol/L Results Thirty-six cases were performed a 16 weeks follow-up and no one lost.After 4 months OADs treatment,the levels of fasting

  7. Drug-drug interactions between rosuvastatin and oral antidiabetic drugs occurring at the level of oatp1b1s

    NARCIS (Netherlands)

    Steeg, E. van de; Greupink, R.; Schreurs, M.; Nooijen, I.H.G.; Verhoeck, K.C.M.; Hanemaaijer, R.; Ripken, D.; Monshouwer, M.; Vlaming, M.L.H.; DeGroot, J.; Verwei, M.; Russel, F.G.M.; Huisman, M.T.; Wortelboer, H.M.

    2013-01-01

    Organic anion-transporting polypeptide 1B1 (OATP1B1) is an important hepatic uptake transporter, of which the polymorphic variant OATP1B1*15 (Asn130Asp and Val174Ala) has been associated with decreased transport activity. Rosuvastatin is an OATP1B1 substrate and often concomitantly prescribed with o

  8. Improved stability and antidiabetic potential of insulin containing folic acid functionalized polymer stabilized multilayered liposomes following oral administration

    DEFF Research Database (Denmark)

    Agrawal, Ashish Kumar; Harde, Harshad; Thanki, Kaushik;

    2014-01-01

    The present study reports the folic acid (FA) functionalized insulin loaded stable liposomes with improved bioavailability following oral administration. Liposomes were stabilized by alternating coating of negatively charged poly(acrylic acid) (PAA) and positively charged poly(allyl amine...

  9. Polymeric Micro- and Nanofabricatced Devices for Oral Drug Delivery

    Science.gov (United States)

    Fox, Cade Brylee

    While oral drug administration is by far the most preferred route, it is accompanied by many barriers that limit drug uptake such as the low pH of the stomach, metabolic and proteolytic enzymes, and limited permeability of the intestinal epithelium. As a result, many drugs ranging from small molecules to biological therapeutics have limited oral bioavailability, precluding them from oral administration. To address this issue, microfabrication has been applied to create planar, asymmetric devices capable of binding to the lining of the gastrointestinal tract and releasing drug at high concentrations, thereby increasing oral drug uptake. While the efficacy of these devices has been validated in vitro and in vivo, modifying their surfaces with nanoscale features has potential to refine their properties for enhanced drug delivery. This dissertation first presents an approach to fabricate polymeric microdevices coated with nanowires in a rapid, high throughput manner. The nanowires demonstrate rapid drug localization onto the surface of these devices via capillary action and increased adhesion to epithelial tissue, suggesting that this fabrication technique can be used to create devices with enhanced properties for oral drug delivery. Also presented are microdevices sealed with nanostraw membranes. The nanostraw membranes provide sustained drug release by limiting drug efflux from the devices, prevent drug degradation by limiting influx of outside biomolecules, and enhance device bioadhesion by penetrating into the mucus layer of the intestinal lining. Finally, an approach that dramatically increases the capacity and efficiency of drug loading into microdevices over previous methods is presented. A picoliter-volume printer is used to print drug directly into device reservoirs in an automated fashion. The technologies presented here expand the capabilities of microdevices for oral drug delivery by incorporating nanoscale structures that enhance device bioadhesion

  10. ORGANIZATION OF AVAILABILITY OF THE CIRCULATION OF ANTIDIABETIC MEDICINES BASED ON PHARMACEUTICAL LAW IN UKRAINE

    Directory of Open Access Journals (Sweden)

    Zbrozhek SI

    2016-12-01

    Full Text Available Introduction. In recent years as the global problem of healthcare in many countries acts diabetes, number of patients with this disease is growing and is already 4-6% of the population in developed countries. These indicators enable WHO experts include diabetes to one of the four priority non-infectious diseases and non-infectious epidemic of the 21st century. Because of chronic disease of diabetes decreases the quality of life of citizens, develops related diseases such as stroke, heart attack, blindness, kidney failure, amputation of the lower extremities causing deaths. Therefore, programs to combat diabetes and its prevention is a priority for national healthcare systems without exception countries. Materials and methods. Circulation of the registered antidiabetic medicines in Ukraine during pricing and delivery (example; forensic and pharmaceutical practice of the complaints and appeals on the availability for them of the antidiabetic medicines; pricing characteristics of the antidiabetic medicines over the period of 2012–2015. Methods: normative and legal, documentary, bibliographic, statistical, comparative, forensic and pharmaceutical, graphical analysis. Results and discussion. The study of organization of circulation of the antidiabetic medicines requires a systematic approach from the organizational, legal and forensic and pharmaceutical research. Today in Ukraine the arsenal of drugs for the treatment of diabetes presented with more than 85 registered antidiabetic drugs for trade names, of which 60% – insulin, and the remaining 40% – oral hypoglycemic drugs offered in a 210 release forms. Given forensic and pharmaceutical example shows that the barrier, which reduces the availability of antidiabetic medicines for diabetics at discounted prescription is mandatory registration of wholesale prices, because that price mechanism of registration by the Ministry of Healthcare of Ukraine interferes with the right of privileged

  11. Analysis of the use of drugs in cardiovascular and antidiabetic primary health care according to age - doi: 10.4025/actascihealthsci.v35i1.10694

    Directory of Open Access Journals (Sweden)

    Marcos Aparecido Sarria Cabrera

    2013-03-01

    Full Text Available The population of elderly and non-elderly users of a Basic Health Unit (UBS was interviewed regarding the use of cardiovascular and anti-diabetic medications, as well as the adverse effects that were noted. Hypertension and diabetes mellitus are conditions involving complications and compromise the quality of life of patients. The objective was to build a profile of these users. The cross-sectional study was carried out on patients older than 18 years of age and users of cardiovascular or anti-diabetic drugs in Centro Social Urbano UBS, located in Londrina – PR, Brazil. The result revealed the following statistically significant variables: lower use of beta blockers (p = 0.012 and metformin (p = 0.05 among the elderly compared to the overall average, and higher acetylsalicylic acid (ASA (p = 0.006 use in people over 64 years of age. Reported adverse symptoms were lower among those over 64 years old (p = 0.03. Angiotensin-converting enzyme (ACE inhibitors are the most used (63.5%, followed by diuretics (54.9% and beta-blockers (27.7%. Among diabetic patients, 23.2% were using biguanides and 15.9% sulfonylureas; only 6.6% were insulin-dependent. The conclusion is that drug therapies within the sample were mostly in accordance with current guidelines.  

  12. Analytical evaluation of five oral fluid drug testing devices

    OpenAIRE

    Isalberti, Cristina; Van Stechelman, Sylvie; Legrand, Sara-Ann; Van der Linden, Gertrude; Verstraete, Alain

    2010-01-01

    Introduction: The correlation with blood drug presence and the easiness of sample collection make oral fluid an ideal matrix for roadside drug tests targeting impaired drivers. Aim: To evaluate the reliability of five oral fluid testing devices: Varian OraLab®6, Dräger DrugTest® 5000, Cozart® DDS 806, Mavand RapidSTAT® and Innovacon OrAlert. Method: More than 760 samples were collected from volunteers either at drug addiction treatment centres or during roadside sessions. Target drug ...

  13. A DETAILED REVIEW ON ORAL MUCOSAL DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Radha Bhati

    2012-03-01

    Full Text Available Oral mucosal drug delivery system is widely applicable as novel site for administration of drug for immediate and controlled release action by preventing first pass metabolism and enzymatic degradation due to GI microbial flora. Oral mucosal drug delivery system provides local and systemic action. In this review, attention is focused to give regarding physiology of oral mucosal including tissue permeability, barriers to permeation and route of permeation, biopharmaceutics of buccal and sublingual absorption, factors affecting drug absorption, detailed information of penetration enhancers, design of oral mucosal drug delivery system and role of mucoadhesion and various theories of bioadhesion. Evaluation techniques and selection of animal model for in-vivo studies are also discussed.

  14. Oral controlled release drug delivery system and Characterization of oral tablets; A review

    Directory of Open Access Journals (Sweden)

    Muhammad Zaman

    2016-01-01

    Full Text Available Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes diffusion controlled drug delivery systems; dissolution controlled drug delivery systems, osmotically controlled drug delivery systems, ion-exchange controlled drug delivery systems, hydrodynamically balanced systems, multi-Particulate drug delivery systems and microencapsulated drug delivery system. The systems are formulated using different natural, semi-synthetic and synthetic polymers. The purpose of the review is to provide information about the orally controlled drug delivery system, polymers which are used to formulate these systems and characterizations of one of the most convenient dosage form which is the tablets. 

  15. 76 FR 59023 - Oral Dosage Form New Animal Drugs; Tylosin

    Science.gov (United States)

    2011-09-23

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Tylosin... drug application (ANADA) filed by Cross Vetpharm Group, Ltd. The ANADA provides for use of tylosin..., Dublin 24, Ireland, filed ANADA 200-455 for use of TYLOMED-WS (tylosin tartrate), a water soluble powder...

  16. Performance Evaluation of Mucoadhesive Potential of Sodium Alginate on Microspheres Containing an Anti-Diabetic Drug: Glipizide

    Directory of Open Access Journals (Sweden)

    Yaswanth Allamneni

    2012-04-01

    Full Text Available The objective of the present investigation was to design mucoadhesive microspheres to achieve a substantial increase in length of stay of the drug in the GI tract of glipizide for treatment of type 2 diabetes mellitus. Glipizide is a second-generation sulfonylurea derivative used for the treatment of type II diabetes. Its short biological half-life (0.3 ± 0.7 h necessitates the need to be administered in two or three doses of 2.5-10 mg per day. Mucoadhesive microsphere exhibit a prolonged residence time at the site of application and facilitate an intimate contact with the underlying absorption surface and thus contribute to improved or better therapeutic performance of drug. It would, therefore be advantageous to have means for providing an intimate contact of the drug delivery system with the absorbing membranes. In the present study, alginate based mucoadhesive microspheres of were prepared by ionotropic external gelation technique utilizing calcium chloride (CaCl2 as a cross linking agent, to take the advantage of swelling and mucoadhesive property of alginate beads for improving the oral delivery of glipizide. Interaction studies performed using FTIR spectroscopy and DSC revealed that there was no drug to polymer interactions. The prepared microspheres are discrete, spherical and free flowing which was characterized by entrapment efficiency, particle size, micromeritic properties, in-vitro release behavior, scanning electron microscopy (SEM, in-vitro wash off test etc. Depending upon the variability in the concentration of sodium alginate, time of cross linking agent, the factors like particle size, and incorporation efficiency and release rate and mucoadhesion properties of microspheres varies. It was observed that increasing the polymer concentration along with the cross-linking time given the better affect on microspheres characteristic and percentage release of drug. Formulation F8 containing 5% w/v sodium alginate was selected as best

  17. Guidelines for European workplace drug testing in oral fluid.

    Science.gov (United States)

    Cooper, Gail; Moore, Christine; George, Claire; Pichini, Simona

    2011-05-01

    Over the past decade, oral fluid has established itself as a robust testing matrix for monitoring drug use or misuse. Commercially available collection devices provide opportunities to collect and test oral fluid by the roadside and near-patient testing with both clinical and criminal justice applications. One of the main advantages of oral fluid relates to the collection of the matrix which is non-invasive, simple, and can be carried out under direct observation making it ideal for workplace drug testing. Laboratories offering legally defensible oral fluid workplace drug testing must adhere to national and international quality standards (ISO/IEC 17025); however, these standards do not address issues specific to oral fluid testing. The European Workplace Drug Testing Society (EWDTS) recognizes the importance of providing best practice guidelines to organizations offering testing and those choosing to use oral fluid drug testing to test their employees. The aim of this paper is to present the EWDTS guidelines for oral fluid workplace drug testing. Copyright © 2011 John Wiley & Sons, Ltd.

  18. A novel oral dual amylin and calcitonin receptor agonist (KBP-042) exerts antiobesity and antidiabetic effects in rats

    DEFF Research Database (Denmark)

    Andreassen, Kim V; Feigh, Michael; Hjuler, Sara T

    2014-01-01

    The present study investigated a novel oral dual amylin and calcitonin receptor agonist (DACRA), KBP-042, in head-to-head comparison with salmon calcitonin (sCT) with regard to in vitro receptor pharmacology, ex vivo pancreatic islet studies, and in vivo proof of concept studies in diet-induced o......The present study investigated a novel oral dual amylin and calcitonin receptor agonist (DACRA), KBP-042, in head-to-head comparison with salmon calcitonin (sCT) with regard to in vitro receptor pharmacology, ex vivo pancreatic islet studies, and in vivo proof of concept studies in diet......-induced obese (DIO) and Zucker diabetic fatty (ZDF) rats. In vitro, KBP-042 demonstrated superior binding affinity and activation of amylin and calcitonin receptors, and ex vivo, KBP-042 exerted inhibitory action on stimulated insulin and glucagon release from isolated islets. In vivo, KBP-042 induced...... a superior attenuation of diabetic hyperglycemia and alleviated impaired glucose and insulin tolerance. Concomitantly, KBP-042 preserved insulinotropic and induced glucagonostatic action, ultimately preserving pancreatic insulin and glucagon content. In conclusion, oral KBP-042 is a novel DACRA, which exerts...

  19. Novel engineered systems for oral, mucosal and transdermal drug delivery.

    Science.gov (United States)

    Li, Hairui; Yu, Yuan; Faraji Dana, Sara; Li, Bo; Lee, Chi-Ying; Kang, Lifeng

    2013-08-01

    Technological advances in drug discovery have resulted in increasing number of molecules including proteins and peptides as drug candidates. However, how to deliver drugs with satisfactory therapeutic effect, minimal side effects and increased patient compliance is a question posted before researchers, especially for those drugs with poor solubility, large molecular weight or instability. Microfabrication technology, polymer science and bioconjugate chemistry combine to address these problems and generate a number of novel engineered drug delivery systems. Injection routes usually have poor patient compliance due to their invasive nature and potential safety concerns over needle reuse. The alternative non-invasive routes, such as oral, mucosal (pulmonary, nasal, ocular, buccal, rectal, vaginal), and transdermal drug delivery have thus attracted many attentions. Here, we review the applications of the novel engineered systems for oral, mucosal and transdermal drug delivery.

  20. Fabrication and loading of microcontainers for oral drug delivery

    DEFF Research Database (Denmark)

    Petersen, Ritika Singh

    is achieved. Characterization of spin coating of drug-polymer films is thoroughly performed using microscopy, profilometry, differential scanning calorimetry, Raman spectroscopy, X-ray diffraction and microdissolution release tests. These films are applied for loading of microcontainers. Furosemide which......Oral drug delivery is considered as the most patient compliant delivery route. However, it faces many obstacles, especially due to the ever-increasing number of drugs that are poorly soluble and barely absorbed in the gastro-intestinal tract. Moreover, drugs can degrade in the harsh acidic...... environment of stomach before they reach the intestine. These issues lead to reduced bioavailability of active ingredients. To combat that novel oral drug delivery systems have been developed. Some of these systems that have gained significant interest in this field are reservoir based drug delivery...

  1. Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs

    DEFF Research Database (Denmark)

    Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse;

    2015-01-01

    are summarized. Additionally, the paper provides an overview of recent studies on characterization of solid drug carriers for peptide/protein drugs, drug distribution in particles, drug release and stability in simulated GI fluids, as well as the absorption of peptide/protein drugs in cell-based models. The use......Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe...... biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral...

  2. Drug: D10264 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available of oral blood glucose lowering drugs A10BD11 Metformin and linagliptin D10264 Linagliptin - metformin hydrochloride mixt PubChem: 163312295 ... ...formin hydrochloride [DR:D00944] Antidiabetic [DS:H00409] ATC code: A10BD11 Anatomi...D10264 Mixture, Drug Linagliptin - metformin hydrochloride mixt; Jentaduet (TN) Linagliptin [DR:D09566], Met

  3. Drug: D10261 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10261 Mixture, Drug Metformin hydrochloride - sitagliptin phosphate mixt; Janumet (TN) Metformin hydr...ochloride [DR:D00944], Sitagliptin phosphate hydrate [DR:D06645] Antidiabetic [DS:H00409]...SULINS A10BD Combinations of oral blood glucose lowering drugs A10BD07 Metformin and sitagliptin D10261 Metformin hydrochloride - sitagliptin phosphate mixt PubChem: 163312292 ...

  4. Biopharmaceutical aspects of oral drug delivery

    NARCIS (Netherlands)

    Faassen, Werenfriedus Adrianus

    2004-01-01

    Most drugs display their therapeutic activity on specific places in the human body and should reach the systemic circulation in order to be transported towards the site of action. Irrespective of the route of administration the same sequence of steps are of relevance for the exposure to a drug: rele

  5. Pharmacokinetic and pharmacodynamic drug interactions between antiretrovirals and oral contraceptives.

    Science.gov (United States)

    Tittle, Victoria; Bull, Lauren; Boffito, Marta; Nwokolo, Nneka

    2015-01-01

    More than 50 % of women living with HIV in low- and middle-income countries are of reproductive age, but there are limitations to the administration of oral contraception for HIV-infected women receiving antiretroviral therapy due to drug-drug interactions caused by metabolism via the cytochrome P450 isoenzymes and glucuronidation. However, with the development of newer antiretrovirals that use alternative metabolic pathways, options for contraception in HIV-positive women are increasing. This paper aims to review the literature on the pharmacokinetics and pharmacodynamics of oral hormonal contraceptives when given with antiretroviral agents, including those currently used in developed countries, older ones that might still be used in salvage regimens, or those used in resource-limited settings, as well as newer drugs. Nucleos(t)ide reverse transcriptase inhibitors (NRTIs), the usual backbone to most combined antiretroviral treatments (cARTs) are characterised by a low potential for drug-drug interactions with oral contraceptives. On the other hand non-NRTIs (NNRTIs) and protease inhibitors (PIs) may interact with oral contraceptives. Of the NNRTIs, efavirenz and nevirapine have been demonstrated to cause drug-drug interactions; however, etravirine and rilpivirine appear safe to use without dose adjustment. PIs boosted with ritonavir are not recommended to be used with oral contraceptives, with the exception of boosted atazanavir which should be used with doses of at least 35 µg of estrogen. Maraviroc, an entry inhibitor, is safe for co-administration with oral contraceptives, as are the integrase inhibitors (INIs) raltegravir and dolutegravir. However, the INI elvitegravir, which is given in combination with cobicistat, requires a dose of estrogen of at least 30 µg. Despite the growing evidence in this field, data are still lacking in terms of large cohort studies, randomised trials and correlations to real clinical outcomes, such as pregnancy rates, in women

  6. Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs

    DEFF Research Database (Denmark)

    Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse

    2015-01-01

    Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe...... biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral...... delivery of peptide/protein drugs and to provide an overview of formulationand characterization strategies. For a better understanding of the challenges in oral delivery of peptide/protein drugs, the composition of GI fluids and the digestion processes of different kinds of excipients in the GI tract...

  7. Drug addiction: self-perception of oral health

    OpenAIRE

    Eduardo Luiz Da-ré; Gabriel Ferreira Bello; Gabriela Pereira Silva; Leandro Araújo Fernandes; Daniela Coelho de Lima

    2015-01-01

    Objective: To report the self-perception of substance-abusing individuals who were in a recovery process regarding sociodemographic conditions and general and oral health. Methods: Descriptive cross-sectional study conducted in a recovery center for drug addiction in Alfenas, Minas Gerais, Brazil, in 2015, with 39 men aged over 18 years old. Data were collected using a semi-structured questionnaire that addressed: socioeconomic status, selfperception of general and oral health, access to dent...

  8. Loading of microcontainers for oral drug delivery

    DEFF Research Database (Denmark)

    Marizza, Paolo

    , they are usually degraded before they are absorbed. These combined factors considerably reduce the bioavailability of many active ingredients. Several strategies have been developed to overcome these challenges. One of them are microfabricated drug delivery devices. Microreservoir based-systems are characterized...... of drugs and with the perspective of mass production. In a first instance, the suitability of inkjet printing as filling method was elucidated. Solutions containing furosemide and lipid based formulations of insulin were dispensed into microcontainers. Secondly, this technique was successfully utilized...... to dispense controlled amounts of polymer into microcontainers. Subsequently, polymer filled-containers were loaded with drug. To achieve this, supercritical impregnation technology was successfully employed. Furthermore, in vitro drug dissolution studies showed that the loading yields and the release...

  9. Rapid on-site TLC-SERS detection of four antidiabetes drugs used as adulterants in botanical dietary supplements.

    Science.gov (United States)

    Zhu, Qingxia; Cao, Yongbing; Cao, Yingying; Chai, Yifeng; Lu, Feng

    2014-03-01

    A novel facile method has been established for rapid on-site detection of antidiabetes chemicals used to adulterate botanical dietary supplements (BDS) for diabetes. Analytes and components of pharmaceutical matrices were separated by thin-layer chromatography (TLC) then surface-enhanced Raman spectroscopy (SERS) was used for qualitative identification of trace substances on the HPTLC plate. Optimization and standardization of the experimental conditions, for example the method used for preparation of silver colloids, the mobile phase, and the concentration of colloidal silver, resulted in a very robust and highly sensitive method which enabled successful detection when the amount of adulteration was as low as 0.001 % (w/w). The method was also highly selective, enabling successful identification of some chemicals in extremely complex herbal matrices. The established TLC-SERS method was used for analysis of real BDS used to treat diabetes, and the results obtained were verified by liquid chromatography-triple quadrupole mass spectrometry (LC-MS-MS). The study showed that TLC-SERS could be used for effective separation and detection of four chemicals used to adulterate BDS, and would have good prospects for on-site qualitative screening of BDS for adulterants.

  10. Honey - A Novel Antidiabetic Agent

    Directory of Open Access Journals (Sweden)

    Omotayo O. Erejuwa, Siti A. Sulaiman, Mohd S. Ab Wahab

    2012-01-01

    Full Text Available Diabetes mellitus remains a burden worldwide in spite of the availability of numerous antidiabetic drugs. Honey is a natural substance produced by bees from nectar. Several evidence-based health benefits have been ascribed to honey in the recent years. In this review article, we highlight findings which demonstrate the beneficial or potential effects of honey in the gastrointestinal tract (GIT, on the gut microbiota, in the liver, in the pancreas and how these effects could improve glycemic control and metabolic derangements. In healthy subjects or patients with impaired glucose tolerance or diabetes mellitus, various studies revealed that honey reduced blood glucose or was more tolerable than most common sugars or sweeteners. Pre-clinical studies provided more convincing evidence in support of honey as a potential antidiabetic agent than clinical studies did. The not-too-impressive clinical data could mainly be attributed to poor study designs or due to the fact that the clinical studies were preliminary. Based on the key constituents of honey, the possible mechanisms of action of antidiabetic effect of honey are proposed. The paper also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent. It makes recommendations for further clinical studies on the potential antidiabetic effect of honey. This review provides insight on the potential use of honey, especially as a complementary agent, in the management of diabetes mellitus. Hence, it is very important to have well-designed, randomized controlled clinical trials that investigate the reproducibility (or otherwise of these experimental data in diabetic human subjects.

  11. [Oral chemotherapy: food-drug interactions].

    Science.gov (United States)

    Santana Martínez, Sara; Marcos Rodríguez, José Antonio; Romero Carreño, Elia

    2015-07-01

    Introducción: el uso de citostáticos orales está cada vez más extendido en oncología. Presenta ventajas importantes, como la comodidad para el paciente, pero también supone nuevos retos que no se planteaban con la terapia intravenosa. Algunos de estos fármacos presentan interacciones con los alimentos, dando lugar a cambios en su biodisponibilidad. Al tratarse de fármacos de estrecho margen terapéutico, pueden dar lugar a alteraciones en su eficacia y/o toxicidad. Objetivos: evaluar el nivel de conocimiento sobre el modo de administración por parte de los pacientes que acuden a la consulta de pacientes externos de oncohematología del hospital de aquellos citostáticos orales que presentan alguna restricción respecto a su consumo con alimentos (deben tomarse o bien en ayunas. o bien con alimentos). Minimizar al máximo la administración incorrecta de los citostáticos dispensados y el riesgo de que se produzcan interacciones con los alimentos, proporcionando información a los pacientes acerca del modo correcto de administración. Material y métodos: una vez identificados los citostáticos orales con restricciones respecto a su consumo con alimentos, además de la información aportada por farmacia, se preguntó a los pacientes la información que habían recibido por parte del médico acerca de cómo debía administrarse el fármaco, el modo en que se lo tomaban finalmente y, en caso de no hacerlo adecuadamente, se les reforzó la información pertinente. En el siguiente ciclo se confirmó si efectivamente el paciente se lo administraba correctamente, en caso de hacerlo previamente de forma incorrecta (intervención aceptada/no aceptada). Resultados y conclusiones: un 40% de los pacientes entrevistados se administraban el fármaco incorrectamente. Los resultados muestran una gran diversidad en función del fármaco dispensado. Se realizaron un total de 39 intervenciones, que fueron aceptadas en un 95%. Los datos obtenidos sugieren la necesidad de

  12. Antidiabetic and hypolipidemic activities of Kigelia pinnata flowers extract in streptozotocin induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Kumar S; Kumar V; Prakash OM

    2012-01-01

    Objective:To evaluate antidiabetic and hypolipidemic activities of Kigelia pinnata methanolic flowers extract in streptozotocin (STZ) induced diabetic wistar rat. Methods: Rats were made diabetic by a single dose of STZ at 60 mg/kg body weight i.p. The blood glucose level was checked before and 72 h after STZ injection to confirm the development of diabetes. The flower extract and glibenclamide were administered orally at the doses of 250 and 500 mg/kg body weight for 21 days. Results:Daily oral treatment with the extract and standard drug for 21 days significantly reduced blood glucose, serum cholesterol and triglycerides levels. High density lipoprotein-cholesterol level was found to be improved (P<0.01) as compared to diabetic control group. Conclusions:It is concluded that Kigellia pinnata flowers extract have significant antidiabetic and hypolipidemic effect.

  13. AN OVERVIEW ON VARIOUS APPROACHES TO ORAL CONTROLLED DRUG DELIVERY SYSTEM VIA GASTRORETENTIVE DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Bhalla.Neetika

    2012-04-01

    Full Text Available In recent years scientific and technological advancements have been made in the research and development of oral drug delivery system. Oral sustained drug delivery system is complicated by limited gastric residence times (GRTs. In order to understand various physiological difficulties to achieve gastric retention, we have summarized important factors controlling gastric retention. To overcome these limitations, various approaches have been proposed to increase gastric residence of drug delivery systems in the upper part of the gastrointestinal tract includes floating drug dosage systems (FDDS, swelling or expanding systems , mucoadhesive systems , magnetic systems, modified-shape systems, high density system and other delayed gastric emptying devices.

  14. pH-triggered drug release from biodegradable microwells for oral drug delivery

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Nagstrup, Johan; Gordon, Sarah;

    2015-01-01

    Microwells fabricated from poly-L-lactic acid (PLLA) were evaluated for their application as an oral drug delivery system using the amorphous sodium salt of furosemide (ASSF) as a model drug. Hot embossing of PLLA resulted in fabrication of microwells with an inner diameter of 240 μm and a height...... of microwell cavities with an Eudragit® layer prevented drug release in biorelevant gastric medium. An immediate release of the ASSF from coated microwells was observed in the intestinal medium. This pH-triggered release behavior demonstrates the future potential of PLLA microwells as a site-specific oral drug...

  15. New antiplatelet drugs and new oral anticoagulants.

    Science.gov (United States)

    Koenig-Oberhuber, V; Filipovic, M

    2016-09-01

    In our daily anaesthetic practice, we are confronted with an increasing number of patients treated with either antiplatelet or anticoagulant agents. During the last decade, changes have occurred that make the handling of antithrombotic medication a challenging part of anaesthetic perioperative management. In this review, the authors discuss the most important antiplatelet and anticoagulant drugs, the perioperative management, the handling of bleeding complications, and the interpretation of some laboratory analyses related to these agents.

  16. 21 CFR 330.3 - Imprinting of solid oral dosage form drug products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Imprinting of solid oral dosage form drug products... AS SAFE AND EFFECTIVE AND NOT MISBRANDED General Provisions § 330.3 Imprinting of solid oral dosage form drug products. A requirement to imprint an identification code on solid oral dosage form drug...

  17. Self-nanoemulsifying drug delivery systems for oral insulin delivery

    DEFF Research Database (Denmark)

    Li, Ping; Tan, Angel; Prestidge, Clive A

    2014-01-01

    This study aims at evaluating the combination of self-nanoemulsifying drug delivery systems (SNEDDS) and enteric-coated capsules as a potential delivery strategy for oral delivery of insulin. The SNEDDS preconcentrates, loaded with insulin-phospholipid complex at different levels (0, 2.5 and 10% w...

  18. Solid Phospholipid Dispersions for Oral Delivery of Poorly Soluble Drugs

    DEFF Research Database (Denmark)

    Fong, Sophia Yui Kau; Martins, Susana A. M.; Brandl, Martin

    2016-01-01

    Celecoxib (CXB) is a Biopharmaceutical Classification System class II drug in which its oral bioavailability is limited by poor aqueous solubility. Although a range of formulations aiming to increase the solubility of CXB have been developed, it is not completely understood, whether (1) an increase...

  19. Comparison of Urine and Oral Fluid for Workplace Drug Testing.

    Science.gov (United States)

    Casolin, Armand

    2016-09-01

    To determine the relative detection rates of urine versus oral fluid testing in a safety sensitive industry and the correlation with diagnosed substance use disorders and possible impairment at work. The trial involved 1,500 paired urine and oral fluid tests performed in accordance with Australian Standard/New Zealand Standard (AS/NZS) 4308:2008 and AS 4760:2006. Workers who returned a positive test were screened for substance use disorders, as defined by DSM-5, and for possible impairment at work following that particular episode of substance use. Substances were detected in 3.7% (n = 56) of urine samples and 0.5% (n = 8) of oral fluid samples (p drug or a controlled substance without a clinical indication and prescription. Nine workers tested positive on urine alone, one on oral fluid alone and two on both (p = 0.0114). Of note, 6/11 workers who tested positive on urine had possible impairment at work and 2/11 had a substance use disorder versus 2/3 and 0/3, respectively, who tested positive on oral fluid. Urine drug testing performed in accordance with AS/NZS 4308:2008 is more likely to detect overall substance use and illicit drug use than oral fluid testing conducted in accordance with AS 4760:2006. Urine testing performed in accordance with AS/NZS 4308:2008 may also be more likely to detect workers with possible impairment at work and substance use disorders than oral fluid testing performed in accordance with AS 4760:2006. © The Author 2016. Published by Oxford University Press.

  20. Gymnema sylvestre R. Br. suspension cell extract show antidiabetic potential in Alloxan induced diabetic albino male rats

    Institute of Scientific and Technical Information of China (English)

    R Karthic; S Nagaraj; P Arulmurugan; S Seshadri; R Rengasamy; K Kathiravan

    2012-01-01

    Objective: To study the antidiabetic effects of suspension cell extract of Gymnema sylvestre (G.sylvestre in vitro grown suspension cells of G. sylvestre along with field grown and wild plant leaves of G.sylvestre was tested on alloxan induced diabetic rats. Results: While oral administration of the extracts reduced the glucose content in blood and urine, sugar and lipids in serum significantly (P≤0.05), it also increased the body weight, total haemoglobin and plasma protein content.Conclusions:It can be concluded that G. sylvestre suspension cell extract show excellent) along with field grown and wild plants. Methods: The effect of ethanolic extracts of the antidiabetic potential against alloxan induced diabetic albino male rats therefore be considered as potent antidiabetic drug.

  1. Microcontainers - an oral drug delivery system for poorly soluble drugs

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Petersen, Ritika Singh; Marizza, Paolo

    with polyvinylpyrrolidone (PVP) by inkjet printing followed by supercritical CO2 impregnation of ketoprofen into the PVP matrix. As an alternative filling method, the powder of amorphous sodium salt of furosemide, (ASSF) was filled into the SU-8 microcontainers. The PLLA microcontainers were filled with drug formulation...

  2. The complete control of glucose level utilizing the composition of ketogenic diet with the gluconeogenesis inhibitor, the anti-diabetic drug metformin, as a potential anti-cancer therapy.

    Science.gov (United States)

    Oleksyszyn, Józef

    2011-08-01

    In the animal models of glucose dependent cancer growth, the growth is decreased 15-30% through the use of low-carbohydrate, calorically restricted and/or ketogenic diet. The remaining growth depends on glucose formed by the liver-kidney gluconeogenesis as is the case in the cancer cachexia. It is hypothesized that a new treatment for cancer diseases should be explored which includes the ketogenic diet combined with the inhibition of gluconeogenesis by the anti-diabetic drug metformin.

  3. Orally disintegrating films: A modern expansion in drug delivery system

    Directory of Open Access Journals (Sweden)

    Muhammad Irfan

    2016-09-01

    Full Text Available Over the past few decades, tendency toward innovative drug delivery systems has majorly increased attempts to ensure efficacy, safety and patient acceptability. As discovery and development of new chemical agents is a complex, expensive and time consuming process, so recent trends are shifting toward designing and developing innovative drug delivery systems for existing drugs. Out of those, drug delivery system being very eminent among pediatrics and geriatrics is orally disintegrating films (ODFs. These fast disintegrating films have superiority over fast disintegrating tablets as the latter are associated with the risks of choking and friability. This drug delivery system has numerous advantages over conventional fast disintegrating tablets as they can be used for dysphasic and schizophrenic patients and are taken without water due to their ability to disintegrate within a few seconds releasing medication in mouth. Various approaches are employed for formulating ODFs and among which solvent casting and spraying methods are frequently used. Generally, hydrophilic polymers along with other excipients are used for preparing ODFs which allow films to disintegrate quickly releasing incorporated active pharmaceutical ingredient (API within seconds. Orally disintegrating films have potential for business and market exploitation because of their myriad of benefits over orally disintegrating tablets. This present review attempts to focus on benefits, composition, approaches for formulation and evaluation of ODFs. Additionally, the market prospect of this innovative dosage form is also targeted.

  4. Micro and nano structures for biosensing and oral drug delivery

    DEFF Research Database (Denmark)

    Boisen, Anja

    2014-01-01

    , facilitating electrochemical measurements. In cantilever-­‐based sensing, micrometer sized cantilevers are functionalized on one side with probe molecules. As target analytes bind to the probe molecules the cantilever deflects due to changes in surface stress. This deflection is typically in the nm range...... spectroscopy on picoliter amount of sample. Vibrating micrometer sized strings can be used for efficient and sensitive mass detection and for chemical analysis of single nanoparticles. We will show examples from drug characterization and illustrate how the strings can be read-­‐out using blu-­‐ray optics....... Finally, we will show how agglutination based assays can be handled and read-­‐out using the disc platform – here targeting biomarkers for rapid diagnostics and prognostics. Micrometer sized containers can be used for oral drug delivery. The hypothesis is that oral drug delivery can be improved...

  5. 2003~2005年我院口服降糖药物利用分析%Drug utilization analysis of oral hypoglycemic agents in our hospital during the period of 2003 ~ 2005

    Institute of Scientific and Technical Information of China (English)

    辛海莉; 蔡雯雯; 郭蔚

    2007-01-01

    To assess the drug utilization and tendency of progress of oral hypoglycemic agents in our hospital and to provide references for rational administration clinically. Methods: DDDs, sales quantities, sales expenses and the ratio of sales expenses sequencing to that of DDDs in our hospital during the period of 2003 ~ 2005 were analyzed statistically with the method of DDDs analysis. Results:The top two antidiabetic drugs according to DDDs were melbine ( dimethyl diguanide) and gliclazide three successive years. The DDDs of acarbose increased dramatically. Which blood glucose regulatsry drugs ranked lower, the ratio of sales expenses sequencing to that of DDDs of glipizide and gliclazide controlled release pellets was equal or about, whereas that of rosiglitazone, acarbose(glucobay) and glimepiride was less than 1. Conclusion:The study shows that the drug utilization of oral hypoglycemic agents in our hospital is basically rational and is in accordance with the trend of advancement and drug therapeutic strategies of diabetes mellitus.

  6. Sitagliptin, An Anti-diabetic Drug, Suppresses Estrogen Deficiency-Induced OsteoporosisIn Vivo and Inhibits RANKL-Induced Osteoclast Formation and Bone Resorption In Vitro

    Directory of Open Access Journals (Sweden)

    Chuandong Wang

    2017-06-01

    Full Text Available Postmenopausal osteoporosis is a disease characterized by excessive osteoclastic bone resorption. Some anti-diabetic drugs were demonstrated for anti-osteoclastic bone-loss effects. The present study investigated the skeletal effects of chronic administration of sitagliptin, a dipeptidyl peptidase IV (DPP IV inhibitor that is increasingly used for type 2 diabetes treatments, in an estrogen deficiency-induced osteoporosis and elucidated the associated mechanisms. This study indicated that sitagliptin effectively prevented ovariectomy-induced bone loss and reduced osteoclast numbers in vivo. It was also indicated that sitagliptin suppressed receptor activator of nuclear factor-κB ligand (RANKL-mediated osteoclast differentiation, bone resorption, and F-actin ring formation in a manner of dose-dependence. In addition, sitagliptin significantly reduced the expression of osteoclast-specific markers in mouse bone-marrow-derived macrophages, including calcitonin receptor (Calcr, dendrite cell-specific transmembrane protein (Dc-stamp, c-Fos, and nuclear factor of activated T-cells cytoplasmic 1 (Nfatc1. Further study indicated that sitagliptin inhibited osteoclastogenesis by suppressing AKT and ERK signaling pathways, scavenging ROS activity, and suppressing the Ca2+ oscillation that consequently affects the expression and/or activity of the osteoclast-specific transcription factors, c-Fos and NFATc1. Collectively, these findings suggest that sitagliptin possesses beneficial effects on bone and the suppression of osteoclast number implies that the effect is exerted directly on osteoclastogenesis.

  7. Dietary Intake as a Link between Obesity, Systemic Inflammation, and the Assumption of Multiple Cardiovascular and Antidiabetic Drugs in Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Bruna Guida

    2013-01-01

    Full Text Available We evaluated dietary intake and nutritional-inflammation status in ninety-six renal transplant recipients, years after transplantation. Patients were classified as normoweight (NW, overweight (OW, and obese (OB, if their body mass index was between 18.5 and 24.9, 25.0 and 29.9, and ≥30 kg/m2, respectively. Food composition tables were used to estimate nutrient intakes. The values obtained were compared with those recommended in current nutritional guidelines. 52% of the patients were NW, 29% were OW, and 19% were OB. Total energy, fat, and dietary n-6 PUFAs intake was higher in OB than in NW. IL-6 and hs-CRP were higher in OB than in NW. The prevalence of multidrug regimen was higher in OB. In all patients, total energy, protein, saturated fatty acids, and sodium intake were higher than guideline recommendations. On the contrary, the intake of unsaturated and n-6 and n-3 polyunsaturated fatty acids and fiber was lower than recommended. In conclusion, the prevalence of obesity was high in our patients, and it was associated with inflammation and the assumption of multiple cardiovascular and antidiabetic drugs. Dietary intake did not meet nutritional recommendations in all patients, especially in obese ones, highlighting the need of a long-term nutritional support in renal transplant recipients.

  8. Development of a fast high performance liquid chromatographic screening system for eight antidiabetic drugs by an improved methodology of in-silico robustness simulation.

    Science.gov (United States)

    Mokhtar, Hatem I; Abdel-Salam, Randa A; Haddad, Ghada M

    2015-06-19

    Robustness of RP-HPLC methods is a crucial method quality attribute which has gained an increasing interest throughout the efforts to apply quality by design concepts in analytical methodology. Improvement to design space modeling approaches to represent method robustness was the goal of many previous works. Modeling of design spaces regarding to method robustness fulfils quality by design essence of ensuring method validity throughout the design space. The current work aimed to describe an improvement to robustness modeling of design spaces in context of RP-HPLC method development for screening of eight antidiabetic drugs. The described improvement consisted of in-silico simulation of practical robustness testing procedures thus had the advantage of modeling design spaces with higher confidence in estimated of method robustness. The proposed in-silico robustness test was performed as a full factorial design of simulated method conditions deliberate shifts for each predicted point in knowledge space with modeling error propagation. Design space was then calculated as zones exceeding a threshold probability to pass the simulated robustness testing. Potential design spaces were mapped for three different stationary phases as a function of gradient elution parameters, pH and ternary solvent ratio. A robust and fast separation for the eight compounds within less than 6 min was selected and confirmed through experimental robustness testing. The effectiveness of this approach regarding definition of design spaces with ensured robustness and desired objectives was demonstrated.

  9. 21 CFR 310.517 - Labeling for oral hypoglycemic drugs of the sulfonylurea class.

    Science.gov (United States)

    2010-04-01

    ... sulfonylurea class. 310.517 Section 310.517 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Devices § 310.517 Labeling for oral hypoglycemic drugs of the sulfonylurea class. (a) The University Group... to all other sulfonylurea drugs as well. Therefore, the labeling for oral hypoglycemic drugs of...

  10. Anti-diabetic drugs, insulin and metformin, have no direct interaction with hepatitis C virus infection or anti-viral interferon response

    Directory of Open Access Journals (Sweden)

    Mohamad S. Hakim

    2014-01-01

    Full Text Available Hepatitis C virus (HCV infection is associated with insulin resistance (IR and type 2 diabetes (T2D. Chronic HCV patients with IR and T2D appear to have a decreased response to the standard pegylated-interferon-alpha and ribavirin (PEG-IFN/RBV anti-viral therapy. Insulin and metformin are anti-diabetic drugs regularly used in the clinic. A previous in vitro study has shown a negative effect of insulin on interferon signaling. In the clinic, adding metformin to PEG-IFN/RBV therapy was reported to increase the response rate in chronic HCV patients and it has been suggested this effect derives from an improved anti-viral action of interferon. The goal of this study was to further investigate the molecular insight of insulin and metformin interaction with HCV infection and the anti-viral action of interferon. We used two cell culture models of HCV infection. One is a sub-genomic model that assays viral replication through luciferase reporter gene expression. The other one is a full-length infectious model derived from the JFH1 genotype 2a isolate. We found that both insulin and metformin do not affect HCV infection. Insulin and metformin also do not influence the anti-viral potency of interferon. In addition, there is no direct interaction between these two drugs and interferon signaling. Our results do not confirm the previous laboratory observation that insulin interferes with interferon signaling and suggest that classical nutritional signaling through mTOR may be not involved in HCV replication. If metformin indeed can increase the response rate to interferon therapy in patients, our data indicate that this could be mediated via an indirect mechanisms.

  11. Oral fluid for workplace drug testing: laboratory implementation.

    Science.gov (United States)

    Moore, Christine

    2012-02-01

    As oral fluid increases in popularity for workplace testing, due to its easy and observed collection, the ability to adapt existing laboratory instrumentation without further capital investment will allow more facilities to test oral fluid. The European Workplace Drug Testing Society (EWDTS) guidelines for oral fluid testing outline the maximum cut-off concentrations acceptable under the workplace drug testing programme. The recommended cut-off values may be subject to change as advances in technology or other considerations warrant identification of these substances at different concentrations; however, the instrumentation currently exists for routine screening using immunoassay and confirmation by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography with tandem mass spectral detection (LC-MS/MS) so laboratories can easily implement oral fluid analysis in their current systems. Immunoassays for the detection of the drug classes at recommended levels have been developed using various collection devices and different formats: liquid reagent chemistries and enzyme-linked immunosorbent assay (ELISA) platforms. Immunoassays provide faster turnaround than mass spectral methods particularly when the number of specimens increases. Since the guidelines state that positive immunoassay results should not be reported without confirmation, fully validated methods using LC-MS/MS and/or GC-MS for all drugs are also widely available. All proposed concentrations are easily achievable using MS instruments currently in testing laboratories; however, the likelihood of a low number of positive specimens in workplace populations allows the test facility to screen specimens in a cost-effective manner using immunoassay, while ensuring scientific credibility and defensibility by confirming the positive results with a second test. Copyright © 2011 John Wiley & Sons, Ltd.

  12. Diabetes mellitus:An overview on its pharmacological aspects and reported medicinal plants having antidiabetic activity

    Institute of Scientific and Technical Information of China (English)

    Patel DK; Kumar R; Laloo D; Hemalatha S

    2012-01-01

    Diabetes mellitus is not a single disease but is a group of metabolic disorders affecting a huge number of population in the world. It is mainly characterized by chronic hyperglycemia, resulting from defects in insulin secretion or insulin action. It is predicated that the number of diabetes person in the world could reach upto 366 million by the year 2030. Even though the cases of diabetes are increasing day by day, except insulin and oral hypoglycemic drugs no other way of treatment has been successfully developed so far. Thus, the objective of the present review is to provide an insight over the pathophysiological and etiological aspects of diabetes mellitus along with the remedies available for this metabolic disorder. The review also contains brief idea about diabetes mellitus and the experimental screening model with their relevant mechanism and significance mainly used nowadays. Alloxan and streptozotocin are mainly used for evaluating the antidiabetic activity of a particular drug. This review contain list of medicinal plants which have been tested for their antidiabetic activity in the alloxan induced diabetic rat model. From the available data in the literature, it was found that plant having antidiabetic activity is mainly due to the presence of the secondary metabolite. Thus, the information provided in this review will help the researchers for the development of an alternative methods rather than insulin and oral hypoglycemic agents for the treatment of diabetes mellitus, which will minimize the complication associated with the diabetes and related disorder.

  13. Review of drug treatment of oral submucous fibrosis.

    Science.gov (United States)

    Chole, Revant H; Gondivkar, Shailesh M; Gadbail, Amol R; Balsaraf, Swati; Chaudhary, Sudesh; Dhore, Snehal V; Ghonmode, Sumeet; Balwani, Satish; Mankar, Mugdha; Tiwari, Manish; Parikh, Rima V

    2012-05-01

    This study undertook a review of the literature on drug treatment of oral submucous fibrosis. An electronic search was carried out for articles published between January 1960 to November 2011. Studies with high level of evidence were included. The levels of evidence of the articles were classified after the guidelines of the Oxford Centre for Evidence-Based Medicine. The main outcome measures used were improvement in oral ulceration, burning sensation, blanching and trismus. Only 13 publications showed a high level of evidence (3 randomized controlled trials and 10 clinical trials/controlled clinical trials), with a total of 1157 patients. Drugs like steroids, hyaluronidase, human placenta extracts, chymotrypsin and collagenase, pentoxifylline, nylidrin hydrochloride, iron and multivitamin supplements including lycopene, have been used. Only systemic agents were associated with few adverse effects like gastritis, gastric irritation and peripheral flushing with pentoxifylline, and flushingly warm skin with nylidrin hydrochloride; all other side-effects were mild and mainly local. Few studies with high levels of evidence were found. The drug treatment that is currently available for oral submucous fibrosis is clearly inadequate. There is a need for high-quality randomized controlled trials with carefully selected and standardized outcome measures.

  14. Uso de anti-hipertensivos e antidiabéticos por idosos: inquérito em Belo Horizonte, Minas Gerais, Brasil Use of anti-hypertensive and anti-diabetic drugs by the elderly: a survey in Belo Horizonte, Minas Gerais State, Brazil

    Directory of Open Access Journals (Sweden)

    Mônica de Fátima Gontijo

    2012-07-01

    Full Text Available A preocupação com efeitos prejudiciais do uso de medicamentos por idosos tem motivado estudos com o objetivo de identificar problemas nessa utilização. Realizou-se um inquérito domiciliar entre aposentados, com idade > 60 anos, residentes em Belo Horizonte, Minas Gerais, Brasil (2003, que declararam ter diabetes ou hipertensão arterial. A qualidade do uso de medicamentos anti-hipertensivos e antidiabéticos foi avaliada com base em redundância, associações medicamentosas e fármacos inapropriados. Entre os 283 (89% idosos autodeclarados hipertensos, em uso de farmacoterapia, 68,2% utilizavam diuréticos, e 37,8% utilizavam IECA. Entre os 22 (64,7% autodeclarados diabéticos sob farmacoterapia, 45,5% utilizavam insulina, e 77,3%, antidiabéticos orais. Entre os 89 autodeclarados diabéticos hipertensos, 80 (90% utilizavam anti-hipertensivos, e 51 (57,3%, antidiabéticos. Observou-se o uso de associações medicamentosas, medicamentos redundantes ou inadequados, o que indica a necessidade de seguimento de protocolos terapêuticos e maior atenção à saúde dos pacientes idosos.Concern over the harmful effects of drug use by the elderly has motivated studies aimed at identifying problems in such utilization. This was a household survey with retirees aged > 60 years living in Belo Horizonte, Minas Gerais State, Brazil, in 2003, who reported having a diagnosis of diabetes and/or hypertension. Quality of anti-hypertensive and anti-diabetic medication was measured by redundancy, combinations of drugs, and inappropriate drugs. Among 283 elderly patients (89% with self-reported hypertension and use of anti-hypertensive pharmacotherapy, 68.2% were using diuretics and 37.8% ACE inhibitors. Among the 22 (64.7% self-reported diabetic patients under pharmacotherapy, 45.5% were using insulin and 77.3% oral anti-diabetic agents. Among the 89 self-reported diabetic and hypertensive patients, 80 (90% were using anti-hypertensive drugs and 51 (57.3% anti-diabetic

  15. Microfluidic Assembly of a Multifunctional Tailorable Composite System Designed for Site Specific Combined Oral Delivery of Peptide Drugs.

    Science.gov (United States)

    Araújo, Francisca; Shrestha, Neha; Shahbazi, Mohammad-Ali; Liu, Dongfei; Herranz-Blanco, Bárbara; Mäkilä, Ermei M; Salonen, Jarno J; Hirvonen, Jouni T; Granja, Pedro L; Sarmento, Bruno; Santos, Hélder A

    2015-08-25

    Multifunctional tailorable composite systems, specifically designed for oral dual-delivery of a peptide (glucagon-like peptide-1) and an enzymatic inhibitor (dipeptidyl peptidase 4 (DPP4)), were assembled through the microfluidics technique. Both drugs were coloaded into these systems for a synergistic therapeutic effect. The systems were composed of chitosan and cell-penetrating peptide modified poly(lactide-co-glycolide) and porous silicon nanoparticles as nanomatrices, further encapsulated in an enteric hydroxypropylmethylcellulose acetylsuccinate polymer. The developed multifunctional systems were pH-sensitive, inherited by the enteric polymer, enabling the release of the nanoparticles only in the simulated intestinal conditions. Moreover, the encapsulation into this polymer prevented the degradation of the nanoparticles' modifications. These nanoparticles showed strong and higher interactions with the intestinal cells in comparison with the nonmodified ones. The presence of DPP4 inhibitor enhanced the peptide permeability across intestinal cell monolayers. Overall, this is a promising platform for simultaneously delivering two drugs from a single formulation. Through this approach peptides are expected to increase their bioavailability and efficiency in vivo both by their specific release at the intestinal level and also by the reduced enzymatic activity. The use of this platform, specifically in combination of the two antidiabetic drugs, has clinical potential for the therapy of type 2 diabetes mellitus.

  16. COST-EFFECTIVENESS ANALYSIS OF ANTI-DIABETIC THERAPY IN A UNIVERSITY TEACHING HOSPITAL

    OpenAIRE

    Giwa Abdulganiyu; Tayo Fola

    2014-01-01

    Purpose: To conduct cost-effectiveness analysis of anti-diabetic therapy in a University Teaching Hospital in 2010. Methods: A retrospective review of selected case-notes was conducted. World Health Organization Defined Daily Dose Method of evaluating drug use and probability method for potential effectiveness of antidiabetic therapeutic options from literature analysis was employed in determining cost-effectiveness of each anti-diabetic therapeutic option identified from anti-diabetic dru...

  17. Predicting Noninsulin Antidiabetic Drug Adherence Using a Theoretical Framework Based on the Theory of Planned Behavior in Adults With Type 2 Diabetes: A Prospective Study.

    Science.gov (United States)

    Zomahoun, Hervé Tchala Vignon; Moisan, Jocelyne; Lauzier, Sophie; Guillaumie, Laurence; Grégoire, Jean-Pierre; Guénette, Line

    2016-04-01

    Understanding the process behind noninsulin antidiabetic drug (NIAD) nonadherence is necessary for designing effective interventions to resolve this problem. This study aimed to explore the ability of the theory of planned behavior (TPB), which is known as a good predictor of behaviors, to predict the future NIAD adherence in adults with type 2 diabetes. We conducted a prospective study of adults with type 2 diabetes. They completed a questionnaire on TPB variables and external variables. Linear regression was used to explore the TPB's ability to predict future NIAD adherence, which was prospectively measured as the proportion of days covered by at least 1 NIAD using pharmacy claims data. The interaction between past NIAD adherence and intention was tested. The sample included 340 people. There was an interaction between past NIAD adherence and intention to adhere to the NIAD (P = 0.032). Intention did not predict future NIAD adherence in the past adherers and nonadherers groups, but its association measure was high among past nonadherers (β = 5.686, 95% confidence interval [CI] -10.174, 21.546). In contrast, intention was mainly predicted by perceived behavioral control both in the past adherers (β = 0.900, 95% CI 0.796, 1.004) and nonadherers groups (β = 0.760, 95% CI 0.555, 0.966). The present study suggests that TPB is a good tool to predict intention to adhere and future NIAD adherence. However, there was a gap between intention to adhere and actual adherence to the NIAD, which is partly explained by the past adherence level in adults with type 2 diabetes.

  18. Drug addiction: self-perception of oral health

    Directory of Open Access Journals (Sweden)

    Eduardo Luiz Da-ré

    2015-12-01

    Full Text Available Objective: To report the self-perception of substance-abusing individuals who were in a recovery process regarding sociodemographic conditions and general and oral health. Methods: Descriptive cross-sectional study conducted in a recovery center for drug addiction in Alfenas, Minas Gerais, Brazil, in 2015, with 39 men aged over 18 years old. Data were collected using a semi-structured questionnaire that addressed: socioeconomic status, selfperception of general and oral health, access to dental care, relationship with the dentist, and other issues. In order to assess the self-perception of oral health, the variable was dichotomized into “satisfactory” and “unsatisfactory”, which refer to what the individual acknowledges as a good or poor condition of oral health, using Fisher’s exact test with 5% significance level. Results: Most frequent diseases were depression, 35.90% (n=14, insomnia, 35.9%, (n=14 and recurring headache (23.1%; n=9; however, 61.50% (n=24 of the participants reported not getting sick easily, which contrasts with their self-perception. Regarding oral health, only 30.50% (n=12 of the participants reported brushing their teeth three times a day; 53.80% (n=21 had dentinal hypersensitivity; 41.00% (n=16 had dry mouth and bad breath; 30.80% (n=12 claimed to have bruxism and reported having one or more loose teeth; 28.20% (n=11 reported clenching the teeth in an exaggerated way, and 33.30% (n=13 reported feeling tooth pain. Conclusion: The self-perception of individuals – under 30 years old, single, white or mulattos – regarding their general health was contradictory, as they rated it as good but have reported depression, insomnia and weight loss; additionally, oral health was considered poor with unsatisfactory conditions, which highlights the harmful effects of substance abuse.

  19. Oral drugs in the treatment of metastatic colorectal cancer.

    Science.gov (United States)

    Kwakman, J J M; Punt, C J A

    2016-07-01

    Intravenous administration of fluoropyrimidine-based chemotherapy has been the cornerstone of treatment in metastatic colorectal cancer (mCRC) for decades. The availability of oral capecitabine has improved the tolerability in monotherapy schedules, and has simplified combination schedules. Since then, other oral drugs have proven efficacy in this setting. We review the available evidence and most recent data concerning oral drugs with proven efficacy in mCRC, including capecitabine, S-1, trifluridine-tipiracil (TAS-102) and regorafenib. The use of capecitabine is widely implemented in the care of mCRC. However, with recent data supporting its prolonged use, the relatively high incidence of hand-foot syndrome (HFS) may impair quality of life. In Asian populations, S-1 is associated with equivalent efficacy but lower incidence of HFS compared to capecitabine. Further studies evaluating the effects of S-1 in Western populations are needed. Both regorafenib and TAS-102 improve the overall survival of patients in whom all other treatment options have failed. Since only a subset of patients appears to benefit, future studies to identify predictive biomarkers are needed.

  20. Oral anticancer drugs in the elderly: an overview.

    Science.gov (United States)

    Lonardi, Sara; Bortolami, Alberto; Stefani, Micaela; Monfardini, Silvio

    2007-01-01

    The increasing number of elderly people in the world population has led to a parallel increase in the number of older cancer patients, with over 45% of all cancers in Europe occurring in patients >70 years of age. The increasing tendency to use oral chemotherapy is thus of interest in the elderly, given that both elderly patients and their physicians prefer to use less complex and toxic regimens when such treatments have equivalent efficacy to more complex regimens. However, data from studies designed to evaluate these therapies in the elderly are currently limited. Factors that must be considered before prescribing oral agents to this subset of patients include age-related physiological changes affecting clinical pharmacology, adherence, the patient's capability to self-administer medications, and safety issues concerning the older patient and his or her caregivers. The idea that elderly patients may benefit from the introduction of oral chemotherapy is very fashionable, but to date there is no proof that this approach is as effective as intravenous therapy in this age group, particularly since randomised trials are lacking. This review discusses these issues and reviews current information about the use of specific oral chemotherapeutic drugs for major neoplastic diseases in the elderly.

  1. Antidiabetic Activity of Self Nanoemulsifying Drug Delivery System from Bay Leaves (Eugenia polyantha Wight) Ethyl Acetate Fraction

    Science.gov (United States)

    Prihapsara, F.; Harini, M.; Widiyani, T.; Artanti, A. N.; Ani, I. L.

    2017-02-01

    Insulin resistance is caused by inability of target tissues to insulin response. Bay leaves (Eugenia polyantha Wight) fraction or extract have been used for the treatment of antidibetic mellitus type-2 resistance insulin (ADMRI) but it has low solubility and bioavailability. To overcome these problems, ethyl acetate fraction of bay leaves was formulated into self nanoemulsifying drug delivery system (SNEDDS) using Virgin Coconut Oil (VCO) as a carrier oil. This study aims to produce nanoherbal medicine, determine effect of nanoherbal preparation derived from bay leaves as an anti-ADMRI. The results showed that the optimum SNEDDS formula was tween 80 : PEG 400 : Virgin Coconut Oil (30% : 60% : 10%) in 5 mL. It has emulsification time 13.00 seconds with the average of droplet size value 84.5 nanometer and zeta potential value ± 0.2 mV. Morphological observation showed the nanoemulsion particles has spherical shaped and stable in different pH media. Hypoglycaemic effect of single dose metformin, SNEDDS, combination a-half dose of SNEEDS with metformin value is 28.3%; 15.6%; 34.6% respectively.

  2. Polysaccharide-based aerogel microspheres for oral drug delivery.

    Science.gov (United States)

    García-González, C A; Jin, M; Gerth, J; Alvarez-Lorenzo, C; Smirnova, I

    2015-03-06

    Polysaccharide-based aerogels in the form of microspheres were investigated as carriers of poorly water soluble drugs for oral administration. These bio-based carriers may combine the biocompatibility of polysaccharides and the enhanced drug loading capacity of dry aerogels. Aerogel microspheres from starch, pectin and alginate were loaded with ketoprofen (anti-inflammatory drug) and benzoic acid (used in the management of urea cycle disorders) via supercritical CO2-assisted adsorption. Amount of drug loaded depended on the aerogel matrix structure and composition and reached values up to 1.0×10(-3) and 1.7×10(-3) g/m(2) for ketoprofen and benzoic acid in starch microspheres. After impregnation, drugs were in the amorphous state in the aerogel microspheres. Release behavior was evaluated in different pH media (pH 1.2 and 6.8). Controlled drug release from pectin and alginate aerogel microspheres fitted Gallagher-Corrigan release model (R(2)>0.99 in both cases), with different relative contribution of erosion and diffusion mechanisms depending on the matrix composition. Release from starch aerogel microspheres was driven by dissolution, fitting the first-order kinetics due to the rigid starch aerogel structure, and showed different release rate constant (k1) depending on the drug (0.075 and 0.160 min(-1) for ketoprofen and benzoic acid, respectively). Overall, the results point out the possibilities of tuning drug loading and release by carefully choosing the polysaccharide used to prepare the aerogels.

  3. Oral Drugs Related with Muscle Wasting and Sarcopenia. A Review.

    Science.gov (United States)

    Campins, Lluis; Camps, Marcella; Riera, Ariadna; Pleguezuelos, Eulogio; Yebenes, Juan Carlos; Serra-Prat, Mateu

    2017-01-01

    Sarcopenia is a geriatric syndrome characterized by progressive and generalized loss of skeletal muscle mass and function. Reported prevalence of this geriatric syndrome, differs depending on the definition, the population and the method used to identify sarcopenia. The causes of sarcopenia are multifactorial, and can include genetic influence, immobility or disuse, endocrine factors, inflammation and nutritional deficiencies. These disorders involve an imbalance between anabolic and catabolic pathways that rules muscle mass. Many drugs taken regularly for common conditions may interact with some mechanisms that can alter the balance between protein synthesis and degradation. This may lead to a harmful or a beneficial effect on muscle mass and strength. Widely prescribed drugs could play an important role during the time of onset and development of sarcopenia. In this paper, we reviewed the current understanding of how can drugs contribute positively or negatively on sarcopenia and muscle wasting. We decided to focus this review on oral common drugs, which are usually prescribed in older adults, leaving aside other drugs as hormone therapy. © 2016 S. Karger AG, Basel.

  4. Novel Nanostructured Solid Materials for Modulating Oral Drug Delivery from Solid-State Lipid-Based Drug Delivery Systems

    National Research Council Canada - National Science Library

    Dening, Tahnee J; Rao, Shasha; Thomas, Nicky; Prestidge, Clive A

    2016-01-01

    Lipid-based drug delivery systems (LBDDS) have gained significant attention in recent times, owing to their ability to overcome the challenges limiting the oral delivery of poorly water-soluble drugs...

  5. Medication adherence to oral anticancer drugs: systematic review.

    Science.gov (United States)

    Huang, Wen-Chuan; Chen, Chung-Yu; Lin, Shun-Jin; Chang, Chao-Sung

    2016-01-01

    Many studies have demonstrated that non-adherence to oral anticancer drugs (OACDs) has challenged treatment efficacy. Otherwise, few validated tools exist to measure patients' adherence to medication regimen in clinical practice. To synthesize previous studies on adherence by cancer patients taking OACDs, especially in targeted therapy, a systematic search of several electronic databases was conducted. We analyzed existing scales' contents for various cancer patients and outcomes of studies assessing adherence. However, a well-validated scale designed particularly for OACD adherence is still lacking. Most adherence scales used in the studies reviewed contain items focused on measuring patients' medication-taking behavior more than their barriers to medication compliance and beliefs. However, non-adherence to OACDs is a complex phenomenon, and drug-taking barriers and patient beliefs significantly affect patients' non-adherence. To understand the key drivers and predisposing factors for non-adherence, we need to develop a well-validated, multidimensional scale.

  6. Fibrin formation and dissolution in women receiving oral contraceptive drugs.

    Science.gov (United States)

    Ball, A P; McKee, P A

    1977-04-01

    Factors affecting fibrin formation and dissolution were compared for 15 women taking combined oral contraceptives and 15 women using nonpharmacological methods of birth control. The two groups were matched for age, body weight, time of blood collection, and day in menstrual cycle; none of the women was receiving other drugs known to affect the blood coagulation or fibrinolytic parameters measured in this study. Fibrinogen concentrations tended to be higher in the experimental group; the degree of fibrinogen degradation, number of fibrin cross-links, and levels of factor XIII and plasminogen were the same for both group. There were significant reductions in antithrombin activity, the euglobulin lysis time, and fibrinolytic inhibitor level in women using oral contraceptives. An estrogen dose effect was suggested for fibrinogen concentration and the degree of antithrombin activity. The increased fibrinolytic activity and decreased fibrinolytic inhibitor levels are consistent with in vitro observations that antithrombin also inhibits plasmin activity. Thus while oral contraceptive-induced depression of antithrombin III could possibly predispose to thrombosis by diminishing the inhibition of the serine protease clotting factors, the concomitant decreased level of plasmin inhibition might balance the system by favoring thrombolysis as well as the digestion and inactivation of certain clotting factors by plasmin.

  7. Antidiabetic Effects of Tea

    Directory of Open Access Journals (Sweden)

    Qiu-Yue Fu

    2017-05-01

    Full Text Available Diabetes mellitus (DM is a chronic endocrine disease resulted from insulin secretory defect or insulin resistance and it is a leading cause of death around the world. The care of DM patients consumes a huge budget due to the high frequency of consultations and long hospitalizations, making DM a serious threat to both human health and global economies. Tea contains abundant polyphenols and caffeine which showed antidiabetic activity, so the development of antidiabetic medications from tea and its extracts is increasingly receiving attention. However, the results claiming an association between tea consumption and reduced DM risk are inconsistent. The advances in the epidemiologic evidence and the underlying antidiabetic mechanisms of tea are reviewed in this paper. The inconsistent results and the possible causes behind them are also discussed.

  8. Comparative efficacy and safety of antidiabetic drug regimens added to metformin monotherapy in patients with type 2 diabetes: a network meta-analysis.

    Directory of Open Access Journals (Sweden)

    Elizabeth S Mearns

    Full Text Available When first line therapy with metformin is insufficient for patients with type 2 diabetes (T2D, the optimal adjunctive therapy is unclear. We assessed the efficacy and safety of adjunctive antidiabetic agents in patients with inadequately controlled T2D on metformin alone.A search of MEDLINE and CENTRAL, clinicaltrials.gov, regulatory websites was performed. We included randomized controlled trials of 3-12 months duration, evaluating Food and Drug Administration or European Union approved agents (noninsulin and long acting, once daily basal insulins in patients experiencing inadequate glycemic control with metformin monotherapy (≥ 1500 mg daily or maximally tolerated dose for ≥ 4 weeks. Random-effects network meta-analyses were used to compare the weighted mean difference for changes from baseline in HbA1c, body weight (BW and systolic blood pressure (SBP, and the risk of developing hypoglycemia, urinary (UTI and genital tract infection (GTI.Sixty-two trials evaluating 25 agents were included. All agents significantly reduced HbA1c vs. placebo; albeit not to the same extent (range, 0.43% for miglitol to 1.29% for glibenclamide. Glargine, sulfonylureas (SUs and nateglinide were associated with increased hypoglycemia risk vs. placebo (range, 4.00-11.67. Sodium glucose cotransporter-2 (SGLT2 inhibitors, glucagon-like peptide-1 analogs, miglitol and empagliflozin/linagliptin significantly reduced BW (range, 1.15-2.26 kg whereas SUs, thiazolindinediones, glargine and alogliptin/pioglitazone caused weight gain (range, 1.19-2.44 kg. SGLT2 inhibitors, empagliflozin/linagliptin, liraglutide and sitagliptin decreased SBP (range, 1.88-5.43 mmHg. No therapy increased UTI risk vs. placebo; however, SGLT2 inhibitors were associated with an increased risk of GTI (range, 2.16-8.03.Adding different AHAs to metformin was associated with varying effects on HbA1c, BW, SBP, hypoglycemia, UTI and GTI which should impact clinician choice when selecting adjunctive

  9. Can the genotype or phenotype of two polymorphic drug metabolising cytochrome P450-enzymes identify oral lichenoid drug eruptions?

    DEFF Research Database (Denmark)

    Kragelund, Camilla; Hansen, Claus; Reibel, Jesper

    2010-01-01

    Lichenoid drug eruptions (LDE) in the oral cavity are adverse drug reactions (ADR) that are impossible to differentiate from oral lichen planus (OLP) as no phenotypic criteria exist. Impaired function of polymorphic cytochrome 450-enzymes (CYPs) may cause increased plasma concentration of some dr...

  10. Antidiabetic potential and secondary metabolites screening of mangrove gastropod Cerithidea obtusa

    Institute of Scientific and Technical Information of China (English)

    Reni Tri Cahyani; Sri Purwaningsih; Azrifitria

    2015-01-01

    Objective: To study the possible effects of Cerithidea obtusa extract as antidiabetic and to screen the secondary metabolites presence. Methods: Antidiabetic activity of Cerithidea obtusa extract was measured in vitro usingα-glucosidase inhibition method. Whereas, secondary metabolites screening was measured qualitatively. Results: The methanol extract had antidiabetic activity (IC50 = 36.40 mg/mL). However, the control drug acarbose had significantly higher antidiabetic activity (IC50 = 0.32 mg/mL). Secondary metabolites screening showed the presence of alkaloids, flavonoids, triterpenoids and saponins. Conclusions: The methanol extract had antidiabetic activity and the presence of alkaloids, flavonoids and triterpenoids might contribute to the activity.

  11. Biodegradable microcontainers as an oral drug delivery system for poorly soluble drugs

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Nagstrup, Johan; Keller, Stephan Sylvest

    2013-01-01

    -equilibration of the dissolution cell with the intestinal medium, a release of furosemide was observed after 1 min with an increased release after 5 min of dissolution. CONCLUSIONS: Biodegradable microcontainers were successfully fabricated and loaded with drug. Coating with Eudragit L-100 proved to be useful for protecting drug......PURPOSE: To fabricate microcontainers in biodegradable polylactic acid (PLLA) polymer films using hot embossing, and investigate the application of fabricated microcontainers as an oral drug delivery system for a poorly soluble drug. METHODS: For fabrication of the PLLA microcontainers, a film...... of PLLA was produced by spin coating. The film was heated above the polymer glass transition temperature (Tg), and a stamp was forced into the film. Following cooling of the film the stamp was removed, exposing the formed microcontainers. Microcontainers were filled with amorphous furosemide sodium salt...

  12. Synthesis and Antidiabetic Evaluation of Benzenesulfonamide Derivatives

    Science.gov (United States)

    Hosseinzadeh, Nouraddin; Seraj, Soodeh; Bakhshi-Dezffoli, Mohamad Ebrahim; Hasani, Mohammad; Khoshneviszadeh, Mehdi; Fallah-Bonekohal, Saeed; Abdollahi, Mohammad; Foroumadi, Alireza; Shafiee, Abbas

    2013-01-01

    The complex metabolic syndrome, diabetes mellitus, is a major human health concern in the world and is estimated to affect 300 million people by the year 2025. Several drugs such as sulfonylureas and biguanides are presently available to reduce hyperglycemia in diabetes mellitus. These drugs have side effects and thus searching for a new class of compounds is essential to overcome this problems. A series of seven novel N-(4-phenylthiazol-2-yl)benzenesulfonamides derivatives were synthesized and assayed in-vivo to investigate their antidiabetic activities by streptozotocin-induced model in rat. These derivatives showed considerable biological efficacy when compared to glibenclamide, a potent and well-known antidiabetic agent, as a reference drug. Four of the compounds were effective, amongst which 13 show more prominent activity at 100 mg/Kg p.o. The experimental results are statistically significant at p < 0.05 level. PMID:24250607

  13. ORAL MULTIPARTICULATE PULSATILE DRUG DELIVERY SYSTEMS: A REVIEW

    Directory of Open Access Journals (Sweden)

    Shaji Jessy

    2011-02-01

    Full Text Available Pulsatile drug delivery aims to release drugs in a planned pattern i.e. at appropriate time and/or at a suitable site of action. Pharmaceutical invention and research are increasingly focusing on delivery systems which enhance desirable therapeutic objectives while minimising side effects. However, in recent pharmaceutical applications involving pulsatile delivery, multiparticulate dosage forms are gaining much favour over single-unit dosage forms because of their potential benefits like predictable gastric emptying, no risk of dose dumping, flexible release patterns and increased bioavailability with less inter- and intra-subject variability. Based on these, the present review aims to study multiparticulate pulsatile delivery systems, for which the Reservoir systems with rupturable polymeric coatings and Reservoir systems with erodible polymer coatings are primarily involved in the control of release. Multiparticulate drug delivery systems provide tremendous opportunities for designing new controlled and delayed release oral formulations, thus extending the frontier of future pharmaceutical development. The development of low density floating multiparticulate pulsed-release dosage forms possessing gastric retention capabilities has also been addressed with increasing focus on the upcoming multiparticulate-pulsatile technologies being exploited on an industrial scale.

  14. Lipophilic drug transfer between liposomal and biological membranes: what does it mean for parenteral and oral drug delivery?

    Science.gov (United States)

    Fahr, Alfred; van Hoogevest, Peter; Kuntsche, Judith; Leigh, Mathew L S

    2006-01-01

    This review presents the current knowledge on the interaction of lipophilic, poorly water soluble drugs with liposomal and biological membranes. The center of attention will be on drugs having the potential to dissolve in a lipid membrane without perturbing them too much. The degree of interaction is described as solubility of a drug in phospholipid membranes and the kinetics of transfer of a lipophilic drug between membranes. Finally, the consequences of these two factors on the design of lipid-based carriers for oral, as well as parenteral use, for lipophilic drugs and lead selection of oral lipophilic drugs is described. Since liposomes serve as model-membranes for natural membranes, the assessment of lipid solubility and transfer kinetics of lipophilic drug using liposome formulations may additionally have predictive value for bioavailability and biodistribution and the pharmacokinetics of lipophilic drugs after parenteral as well as oral administration.

  15. Determinants and associated factors influencing medication adherence and persistence to oral anticancer drugs: a systematic review.

    Science.gov (United States)

    Verbrugghe, M; Verhaeghe, S; Lauwaert, K; Beeckman, D; Van Hecke, A

    2013-10-01

    The use of oral anticancer drugs has increased in modern oncology treatment. The move from intravenous treatments towards oral anticancer drugs has increased the patients' own responsibility to take oral anticancer drugs as being prescribed. High rates of non-adherence to oral anticancer drugs have been reported. A systematic literature review was conducted to gain insight into determinants and associated factors of non-adherence and non-persistence in patients taking oral anticancer therapy. PubMed, Cochrane, Web of Science and Cinahl were systematically searched for studies focusing on determinants and associated factors of medication non-adherence and non-persistence to oral anticancer drugs. The methodological quality of the included studies was assessed by two independent reviewers. No studies were excluded based on the quality assessment. Twenty-five studies were included and systematically reviewed. The quality of the studies was moderate. Associated factors influencing medication non-adherence and non-persistence to oral anticancer drugs are multifactorial and interrelated. Older and younger age, and the influence of therapy related side effects were found to be predominant factors. Non-adherence and non-persistence to oral anticancer drug therapy are complex phenomena. More qualitative research is needed to facilitate the development of patient tailored complex interventions by exploring patients' needs and underlying processes influencing medication non-adherence and non-persistence to oral anticancer drugs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Nanotechnology Based Approaches for Enhancing Oral Bioavailability of Poorly Water Soluble Antihypertensive Drugs

    Directory of Open Access Journals (Sweden)

    Mayank Sharma

    2016-01-01

    Full Text Available Oral administration is the most convenient route among various routes of drug delivery as it offers high patient compliance. However, the poor aqueous solubility and poor enzymatic/metabolic stability of drugs are major limitations in successful oral drug delivery. There are several approaches to improve problems related to hydrophobic drugs. Among various approaches, nanotechnology based drug delivery system has potential to overcome the challenges associated with the oral route of administration. Novel drug delivery systems are available in many areas of medicine. The application of these systems in the treatment of hypertension continues to broaden. The present review focuses on various nanocarriers available in oral drug administration for improving solubility profile, dissolution, and consequently bioavailability of hydrophobic antihypertensive drugs.

  17. New developments and opportunities in oral mucosal drug delivery for local and systemic disease.

    Science.gov (United States)

    Hearnden, Vanessa; Sankar, Vidya; Hull, Katrusha; Juras, Danica Vidović; Greenberg, Martin; Kerr, A Ross; Lockhart, Peter B; Patton, Lauren L; Porter, Stephen; Thornhill, Martin H

    2012-01-01

    The oral mucosa's accessibility, excellent blood supply, by-pass of hepatic first-pass metabolism, rapid repair and permeability profile make it an attractive site for local and systemic drug delivery. Technological advances in mucoadhesives, sustained drug release, permeability enhancers and drug delivery vectors are increasing the efficient delivery of drugs to treat oral and systemic diseases. When treating oral diseases, these advances result in enhanced therapeutic efficacy, reduced drug wastage and the prospect of using biological agents such as genes, peptides and antibodies. These technologies are also increasing the repertoire of drugs that can be delivered across the oral mucosa to treat systemic diseases. Trans-mucosal delivery is now a favoured route for non-parenteral administration of emergency drugs and agents where a rapid onset of action is required. Furthermore, advances in drug delivery technology are bringing forward the likelihood of transmucosal systemic delivery of biological agents.

  18. Pectin-based oral drug delivery to the colon.

    Science.gov (United States)

    Sande, Sverre Arne

    2005-05-01

    This review presents an overview of studies concerning oral formulations intended for site-specific drug delivery to the colon with pectin as the main excipient. The biological aspects covered include gastrointestinal transit and the enzymatic degradation of pectin. Scintigraphic methods demonstrating the functionality of pectin formulations are discussed. The main focus is on the various formulations reported, including matrix tablets, multiparticulate formulations as pellets and hydrogel beads, and pectin-based coatings. Also included is an evaluation of common excipients employed to improve colon specificity by crosslinking or increasing the hydrophobicity. Finally, properties of the pectin molecules that are important for successful formulations are examined. The conclusion is that the studies found in the literature provide an excellent platform for the development of pectin-based colon delivery systems.

  19. Animal versus human oral drug bioavailability: do they correlate?

    Science.gov (United States)

    Musther, Helen; Olivares-Morales, Andrés; Hatley, Oliver J D; Liu, Bo; Rostami Hodjegan, Amin

    2014-06-16

    Oral bioavailability is a key consideration in development of drug products, and the use of preclinical species in predicting bioavailability in human has long been debated. In order to clarify whether any correlation between human and animal bioavailability exist, an extensive analysis of the published literature data was conducted. Due to the complex nature of bioavailability calculations inclusion criteria were applied to ensure integrity of the data. A database of 184 compounds was assembled. Linear regression for the reported compounds indicated no strong or predictive correlations to human data for all species, individually and combined. The lack of correlation in this extended dataset highlights that animal bioavailability is not quantitatively predictive of bioavailability in human. Although qualitative (high/low bioavailability) indications might be possible, models taking into account species-specific factors that may affect bioavailability are recommended for developing quantitative prediction.

  20. Characterization and comparison of sodium-glucose cotransporter 2 inhibitors: Part 2. Antidiabetic effects in type 2 diabetic mice

    Directory of Open Access Journals (Sweden)

    Atsuo Tahara

    2016-07-01

    Full Text Available Previously we investigated the pharmacokinetic, pharmacodynamic, and pharmacologic properties of all six sodium-glucose cotransporter (SGLT 2 inhibitors commercially available in Japan using normal and diabetic mice. We classified the SGLT2 inhibitors with respect to duration of action as either long-acting (ipragliflozin and dapagliflozin or intermediate-acting (tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin. In the present study, antidiabetic effects of repeated administration of these SGLT2 inhibitors in type 2 diabetic mice were investigated. When repeatedly administered for 4 weeks, all SGLT2 inhibitors significantly exhibited antihyperglycemic, antihyperinsulinemic, and pancreas-protective effects, as well as insulin resistance-improving effects. When compared at doses producing comparable reduction in hyperglycemia across all drugs, the antidiabetic effects of ipragliflozin and dapagliflozin were more potent than those of the other four drugs, but these differences among the six drugs were not statistically significant. Further, an oral glucose tolerance test performed after repeated administration demonstrated significant improvement in glucose tolerance only with ipragliflozin and dapagliflozin, implying improved insulin resistance and secretion. Taken together, these findings demonstrate that, although all SGLT2 inhibitors exert antidiabetic effects in type 2 diabetic mice, these pharmacologic effects might be slightly superior with the long-acting drugs, which are able to provide favorable blood glucose control throughout the day.

  1. In vitro characterization of microcontainers as an oral drug delivery system

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Keller, Stephan Sylvest; Petersen, Ritika Singh;

    We here present in vitro studies showing the promise of microcontainers (fabricated in either SU-8 or Poly(lactic acid) (PLLA)) as an oral drug delivery system for the poorly watersoluble drug, furosemide.......We here present in vitro studies showing the promise of microcontainers (fabricated in either SU-8 or Poly(lactic acid) (PLLA)) as an oral drug delivery system for the poorly watersoluble drug, furosemide....

  2. Review of antidiabetic mechanism of Metformin%二甲双胍降糖机制研究进展

    Institute of Scientific and Technical Information of China (English)

    潘小康

    2016-01-01

    [Summary] Metformin is the first‐line oral antidiabetic drug.However ,its antidiabetic mechanism is not well understood.The glucose‐lowering effect of Metformin has been attributed to increase insulin sensitivity and glucose disposal ,suppress hepatic gluconeogenesis and inhibit glucagon action.Metformin can decrease the glucose level by activating AMPK dependent/independent pathway ,but its antidiabetic effect is not limited to this.Here we reviewed antidiabetic mechanism of Metformin.%二甲双胍(M et )是临床一线口服降糖药物,但其降低血糖(BG )的机制还不完全清楚。M et降低BG主要通过增加IS、增加外周组织对葡萄糖(PG )的摄取、抑制肝脏糖异生和拮抗胰升血糖素的作用。Met可通过激活腺苷酸激活蛋白激酶(AMPK)降低BG ,同时,Met也能不依赖AMPK降低BG。本文就M et主要的降糖机制作一综述。

  3. Oral Health of Drug Abusers: A Review of Health Effects and Care

    Directory of Open Access Journals (Sweden)

    Hamed Ekhtiari

    2013-09-01

    Full Text Available Oral health problems, among the most prevalent comorbidities related to addiction, require more attention by both clinicians and policy-makers. Our aims were to review oral complications associated with drugs, oral health care in addiction rehabilitation, health services available, and barriers against oral health promotion among addicts. Drug abuse is associated with serious oral health problems including generalized dental caries, periodontal diseases, mucosal dysplasia, xerostomia, bruxism, tooth wear, and tooth loss. Oral health care has positive effects in recovery from drug abuse: patients’ need for pain control, destigmatization, and HIV transmission. Health care systems worldwide deliver services for addicts, but most lack oral health care programs. Barriers against oral health promotion among addicts include difficulty in accessing addicts as a target population, lack of appropriate settings and of valid assessment protocols for conducting oral health studies, and poor collaboration between dental and general health care sectors serving addicts. These interfere with an accurate picture of the situation. Moreover, lack of appropriate policies to improve access to dental services, lack of comprehensive knowledge of and interest among dental professionals in treating addicts, and low demand for non-emergency dental care affect provision of effective interventions. Management of drug addiction as a multi-organ disease requires a multidisciplinary approach. Health care programs usually lack oral health care elements. Published evidence on oral complications related to addiction emphasizes that regardless of these barriers, oral health care at various levels including education, prevention, and treatment should be integrated into general care services for addicts.

  4. Nanostructured Lipid Carriers Loaded with Baicalin: An Efficient Carrier for Enhanced Antidiabetic Effects.

    Science.gov (United States)

    Shi, Feng; Wei, Zheng; Zhao, Yingying; Xu, Ximing

    2016-01-01

    Recent studies have demonstrated that baicalin has antihyperglycemic effects by inhibiting lipid peroxidation. Baicalin is low hydrophilic and poorly absorbed after oral administration. Thus, a suitable formulation is highly desired to overcome the disadvantages of baicalin. The objective of this work was to prepare baicalin-loaded nanostructured lipid carriers (B-NLCs) for enhanced antidiabetic effects. B-NLCs were prepared by high-pressure homogenization method using Precirol as the solid lipid and Miglyol as the liquid lipid. The properties of the NLCs, such as particle size, zeta potential (ZP), and drug encapsulation efficiency (EE), were investigated. The morphology of NLCs was observed by transmission electron microscopy. In addition, drug release and antidiabetic activity were also studied. The results revealed that B-NLCs particles were uniformly in the nanosize range and of spherical morphology with a mean size of 92 ± 3.1 nm, a ZP of -31.35 ± 3.08 mV, and an EE of 85.29 ± 3.42%. Baicalin was released from NLCs in a sustained manner. In addition, B-NLCs showed a significantly higher antidiabetic efficacy compared with baicalin. B-NLCs described in this study are well-suited for the delivery of baicalin. Currently, herbal medicines have attracted increasing attention as a complementary approach for type 2 diabetesBaicalin has antihyperglycemic effects by inhibiting lipid peroxidationA suitable formulation is highly desired to overcome the disadvantages (poor solubility and low bioavailability) of baicalinNanostructured lipid carriers could enhance the antidiabetic effects of baicalin. Abbreviations used: B-NLCs: Baicalin-Loaded Nanostructured Lipid Carriers, B-SUS: Baicalin Water Suspension, EE: Encapsulation Efficiency, FBG: Fasting Blood Glucose, HbAlc: Glycosylated Hemoglobin, HPLC: High-performance Liquid Chromatography; NLCs: Nanostructured Lipid Carriers, PI: Polydispersity Index, SD: Sprague-Dawley, SLNs: Solid lipid nanoparticles, STZ

  5. Modification de la biodisponibilité orale des médicaments : interactions « Herb-Drugs » « Drugs- Drugs».

    OpenAIRE

    Dossou-Yovo, Flore

    2014-01-01

    Oral dosing is still seen as the silver bullet of drug administration, as it is cheaper andbetter adapted to patient comfort. However, oral route is still inaccessible to many drugssuch as biologics and biosimilars respectively certain anticancer drugs and antiretrovirals(ARV).The aim of this present study was to find new drugs enhancers that improve the oralbioavailability of drugs and xenobiotics. All the studies were realized in vitro using Ussingchambers technic. To achieve the set object...

  6. Harnessing the potential clinical use of medicinal plants as anti-diabetic agents

    Directory of Open Access Journals (Sweden)

    Campbell-Tofte JI

    2012-08-01

    Full Text Available Joan IA Campbell-Tofte,1 Per Mølgaard,2 Kaj Winther11Department of Clinical Biochemistry, Frederiksberg University Hospital, Frederiksberg, Denmark; 2Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, DenmarkAbstract: Diabetes is a metabolic disorder arising from complex interactions between multiple genetic and/or environmental factors. The characteristic high blood sugar levels result from either lack of the hormone insulin (type 1 diabetes, T1D, or because body tissues do not respond to the hormone (type 2 diabetes, T2D. T1D patients currently need exogenous insulin for life, while for T2D patients who do not respond to diet and exercise regimes, oral anti-diabetic drugs (OADs and sometimes insulin are administered to help keep their blood glucose as normal as possible. As neither the administration of insulin nor OADs is curative, many patients develop tissue degenerative processes that result in life-threatening diabetes comorbidities. Several surveys of medicinal plants used as anti-diabetic agents amongst different peoples have been published. Some of this interest is driven by the ongoing diabetes pandemic coupled with the inadequacies associated with the current state of-the-art care and management of the syndrome. However, there is a huge cleft between traditional medicine and modern (Western medicine, with the latter understandably demanding meaningful and scientific validation of anecdotal evidence for acceptance of the former. The main problems for clinical evaluation of medicinal plants with promising anti-diabetic properties reside both with the complexity of components of the plant materials and with the lack of full understanding of the diabetes disease etiology. This review is therefore focused on why research activities involving an integration of Systems Biology-based technologies of pharmacogenomics, metabolomics, and bioinformatics with standard clinical data

  7. Buccal bioadhesive drug delivery--a promising option for orally less efficient drugs.

    Science.gov (United States)

    Sudhakar, Yajaman; Kuotsu, Ketousetuo; Bandyopadhyay, A K

    2006-08-10

    Rapid developments in the field of molecular biology and gene technology resulted in generation of many macromolecular drugs including peptides, proteins, polysaccharides and nucleic acids in great number possessing superior pharmacological efficacy with site specificity and devoid of untoward and toxic effects. However, the main impediment for the oral delivery of these drugs as potential therapeutic agents is their extensive presystemic metabolism, instability in acidic environment resulting into inadequate and erratic oral absorption. Parenteral route of administration is the only established route that overcomes all these drawbacks associated with these orally less/inefficient drugs. But, these formulations are costly, have least patient compliance, require repeated administration, in addition to the other hazardous effects associated with this route. Over the last few decades' pharmaceutical scientists throughout the world are trying to explore transdermal and transmucosal routes as an alternative to injections. Among the various transmucosal sites available, mucosa of the buccal cavity was found to be the most convenient and easily accessible site for the delivery of therapeutic agents for both local and systemic delivery as retentive dosage forms, because it has expanse of smooth muscle which is relatively immobile, abundant vascularization, rapid recovery time after exposure to stress and the near absence of langerhans cells. Direct access to the systemic circulation through the internal jugular vein bypasses drugs from the hepatic first pass metabolism leading to high bioavailability. Further, these dosage forms are self-administrable, cheap and have superior patient compliance. Developing a dosage form with the optimum pharmacokinetics is a promising area for continued research as it is enormously important and intellectually challenging. With the right dosage form design, local environment of the mucosa can be controlled and manipulated in order to

  8. Antidiabetic and antidiarrheal effects of the methanolic extract of Phyllanthus reticulatus leaves in mice

    Institute of Scientific and Technical Information of China (English)

    Mst Hajera Khatun; Mst Luthfun Nesa; Rafikul Islam; Farhana Alam Ripa; Al mamum; Shahin Kadir

    2014-01-01

    Objective: To assess the anti-diabetic and antidiarrheal activity of methanolic extract of Phyllanthus reticulates (P. reticulates) leaves in an animal model. Methods: Phytochemical screening of methanolic extract of P. reticulatus leaves has been performed. Antidiabetic activity have been done by OGTT, normoglycemic hyperglycemia and alloxan induced diabetic mice. Plant extracts (150 mg/kg and 300 mg/kg, b.w.) were administered orally in fasting glucose loaded mice with regard to normal control and in alloxan induced (110 mg/kg body weight i.p.) diabetic mice in comparison with reference drug Metformin hydrochloride (100 mg/kg) during 7 day test period. Antidiarrheal test was conducted by castor oil and magnesium sulfate. Results:Findings confirmed that the continuous post-treatment for 7 days with both extracts showed significant (P<0.05) hypoglycemic activity in OGTT, normoglycemic and alloxan induced mouse models. Castor oil and Magnesium sulfate induced diarrheal test of the extract (200 and 400 mg/kg) has given significant effect in compairing to control diarrheal group. Conclusion:Methanolic extract of P. reticulatus leaves have shown significant antidiabetic and antidiarrheal properties.

  9. Antidiabetic Plants of Iran

    Directory of Open Access Journals (Sweden)

    Ashrafeddin Goushegir

    2011-10-01

    Full Text Available To identify the antidiabetic plants of Iran, a systematic review of the published literature on the efficacy of Iranian medicinal plant for glucose control in patients with type 2 diabetes mellitus was conducted. We performed an electronic literature search of MEDLINE, Science Direct, Scopus, Proquest, Ebsco, Googlescholar, SID, Cochrane Library Database, from 1966 up to June 2010. The search terms were complementary and alternative medicine (CAM, diabetes mellitus, plant (herb, Iran, patient, glycemic control, clinical trial, RCT, natural or herbal medicine, hypoglycemic plants, and individual herb names from popular sources, or combination of these key words. Available Randomized Controlled Trials (RCT published in English or Persian language examined effects of an herb (limited to Iran on glycemic indexes in type 2 diabetic patients were included. Among all of the articles identified in the initial database search, 23 trials were RCT, examining herbs as potential therapy for type 2 diabetes mellitus. The key outcome for antidiabetic effect was changes in blood glucose or HbA1 c, as well as improves in insulin sensitivity or resistance. Available data suggest that several antidiabetic plants of Iran need further study. Among the RCT studies, the best evidence in glycemic control was found in Citrullus colocynthus, Ipomoea betatas, Silybum marianum and Trigonella foenum graecum.

  10. A New Approach to the Oral Administration of Insulin and Other Peptide Drugs

    Science.gov (United States)

    Saffran, Murray; Sudesh Kumar, G.; Savariar, Celin; Burnham, Jeffrey C.; Williams, Frederick; Neckers, Douglas C.

    1986-09-01

    The oral administration of peptide drugs is well known to be precluded by their digestion in the stomach and small intestine. As a new approach to oral delivery, peptide drugs were coated with polymers cross-linked with azoaromatic groups to form an impervious film to protect orally administered drugs from digestion in the stomach and small intestine. When the azopolymer-coated drug reached the large intestine, the indigenous microflora reduced the azo bonds, broke the cross-links, and degraded the polymer film, thereby releasing the drug into the lumen of the colon for local action or for absorption. The ability of the azopolymer coating to protect and deliver orally administered peptide drugs was demonstrated in rats with the peptide hormones vasopressin and insulin.

  11. Dosage Form Developments of Nanosuspension Drug Delivery System for Oral Administration Route.

    Science.gov (United States)

    Chen, Ang; Shi, Ye; Yan, Zhiqiang; Hao, Hongxun; Zhang, Yong; Zhong, Jian; Hou, Huiming

    2015-01-01

    A large amount of new drug candidates are practically insoluble in aqueous solvents and are even simultaneously poorly soluble in organic solvents. Nanosuspension drug delivery system (DDS) was firstly developed in 1994 and has attracted more and more attention as a formation solution for the poorly soluble drugs. By nansizing the poorly soluble drugs, nanosuspensions have several outstanding advantages for drug delivery. Among many administration routes of drug delivery, oral administration is the most preferred route due to its advantages such as ease of ingestion, versatility to accommodate various types of drug candidates, low production cost, high safety, good patient compliance, and pain avoidance. Current marketed pharmaceutical nanosuspension DDS products are mostly for oral administration. This review is to systematically summarize the nanosuspension DDS dosage form developments of poorly soluble drugs for oral administration use.

  12. Treatment of a Tuberculous Empyema with Simultaneous Oral and Intrapleural Antituberculosis Drugs

    Directory of Open Access Journals (Sweden)

    Richard Long

    2008-01-01

    Full Text Available A 71-year-old man was diagnosed with an uncomplicated tuberculous (TB empyema. Differential penetration of anti-TB drugs, believed to explain the phenomenon of acquired drug resistance in TB empyema, was confirmed by measurement of serum and pleural fluid anti-TB drug concentrations. Simultaneous oral and intrapleural anti-TB drugs were administered and a cure was achieved. The present case is discussed in the context of the literature on acquired drug resistance in TB empyema. It is argued that high-end doses of oral drugs or combined oral plus intrapleural drugs, along with tube thoracostomy or intermittent thoracentesis, will cure uncomplicated TB empyema without threatening to induce drug resistance or having to resort to surgery.

  13. Lipid nanocarriers (GeluPearl) containing amphiphilic lipid Gelucire 50/13 as a novel stabilizer: fabrication, characterization and evaluation for oral drug delivery

    Science.gov (United States)

    Date, Abhijit A.; Vador, Nimish; Jagtap, Aarti; Nagarsenker, Mangal S.

    2011-07-01

    Purpose. To evaluate the ability of Gelucire 50/13 (an amphiphilic lipid excipient) to act as a stabilizer for lipid nanocarriers such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) and to establish the ability of Gelucire 50/13 based lipid nanocarriers to improve oral delivery of hydrophobic drugs using repaglinide (RPG) as a model drug. Methods. The ability of Gelucire 50/13 to nanosize various solid lipids was evaluated. The ability of Gelucire 50/13 to yield NLC was evaluated by using Precirol ATO 5 as a model solid lipid and various liquid lipids (oils). Gelucire 50/13 based NLC (GeluPearl) were evaluated for their ability to improve the efficacy of RPG on oral administration in comparison to RPG tablets. The short term stability of RPG-GeluPearl was evaluated at 25 °C/60% RH. Results. Gelucire 50/13 could successfully yield SLN and NLC of various solid lipids, demonstrating its potential to act as a novel stabilizer. DSC studies indicated that Gelucire 50/13 interacts with Precirol ATO 5 and this interaction suppresses polymorphic transitions of both the components. RPG-GeluPearl exhibited significantly higher anti-diabetic activity compared to marketed RPG tablets. RPG-GeluPearl demonstrated good colloidal and chemical stability at the end of 1 month. Indian patent application number 2167/MUM/2008.

  14. Lipid nanocarriers (GeluPearl) containing amphiphilic lipid Gelucire 50/13 as a novel stabilizer: fabrication, characterization and evaluation for oral drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Date, Abhijit A; Nagarsenker, Mangal S [Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E.), Mumbai (India); Vador, Nimish; Jagtap, Aarti, E-mail: mangal_nag511@yahoo.co.in, E-mail: mangal@bcp.edu.in [Department of Pharmacology, Bombay College of Pharmacy, Kalina, Santacruz (E.), Mumbai (India)

    2011-07-08

    Purpose. To evaluate the ability of Gelucire 50/13 (an amphiphilic lipid excipient) to act as a stabilizer for lipid nanocarriers such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) and to establish the ability of Gelucire 50/13 based lipid nanocarriers to improve oral delivery of hydrophobic drugs using repaglinide (RPG) as a model drug. Methods. The ability of Gelucire 50/13 to nanosize various solid lipids was evaluated. The ability of Gelucire 50/13 to yield NLC was evaluated by using Precirol ATO 5 as a model solid lipid and various liquid lipids (oils). Gelucire 50/13 based NLC (GeluPearl) were evaluated for their ability to improve the efficacy of RPG on oral administration in comparison to RPG tablets. The short term stability of RPG-GeluPearl was evaluated at 25 deg. C/60% RH. Results. Gelucire 50/13 could successfully yield SLN and NLC of various solid lipids, demonstrating its potential to act as a novel stabilizer. DSC studies indicated that Gelucire 50/13 interacts with Precirol ATO 5 and this interaction suppresses polymorphic transitions of both the components. RPG-GeluPearl exhibited significantly higher anti-diabetic activity compared to marketed RPG tablets. RPG-GeluPearl demonstrated good colloidal and chemical stability at the end of 1 month.

  15. pH-triggered drug release from biodegradable microwells for oral drug delivery

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Nagstrup, Johan; Gordon, Sarah

    2015-01-01

    of 100 μm. The microwells were filled with ASSF using a modified screen printing technique, followed by coating of the microwell cavities with a gastroresistant lid of Eudragit® L100. The release behavior of ASSF from the coated microwells was investigated using a μ-Diss profiler and a UV imaging system......, and under conditions simulating the changing environment of the gastrointestinal tract. Biorelevant gastric medium (pH 1.6) was employed, after which a change to biorelevant intestinal release medium (pH 6.5) was carried out. Both μ-Diss profiler and UV imaging release experiments showed that sealing...... of microwell cavities with an Eudragit® layer prevented drug release in biorelevant gastric medium. An immediate release of the ASSF from coated microwells was observed in the intestinal medium. This pH-triggered release behavior demonstrates the future potential of PLLA microwells as a site-specific oral drug...

  16. Piperin and piplartin as natural oral anticancer drug

    Directory of Open Access Journals (Sweden)

    Berlian Bidarisugma

    2011-12-01

    Full Text Available Background: Since the last few decades, oral cancer as pathology has become an attention in medicine and dentistry. The majority cases of oral cancer are affecting people with smoking habit and alcohol consumption. Many herbs contain substances which can stop cancer cells proliferation, such as Piper retrofractum/Retrofracti fructus, an herb plant from Piperaceae family which contains piperin and piplartin. Purpose: The purpose of this study was to examine the mechanism of piperin and pilplartin as natural oral anticancer drug. Reviews: Piperin and piplartin has function as antioxidant that can protect body cell from damage caused by free radicals. Piperin works synergistically with another bioactive substance like capsaicin and curcumin. Piperin increase the number of serum and life time of serum from a few nutrition substance like co-enzyme Q10 and beta-carotene. Beta-carotene can catch reactive O2 and peroxil radicals. The activity of anticancer piplartin related with obstruction of proliferation cell rate, observe form Ki67 reduction as antigen in nucleus that associated with G1, S, G2, and M phase in cell cycle. Comparing with piplartin, piperin is more potential to inhibit proliferation rate of Ki67, but piplartin’s antiproliferation mechanism will increase if supported by piperin. Conclusion: Piperin and piplartin contained in Javanese chili are potential for natural oral anticancer, by directly or indirectly suppress tumor cell development by increasing the number of immunity cells (immunomodulator, and by inhibiting cell proliferation with reduction of Ki67, nucleus antigen that associated with G1,S,G2, dan M phase of cell cycle.Latar belakang: Sejak beberapa dekade terakhir, patologi kanker rongga mulut telah banyak menjadi perhatian di bidang kedokteran dan kedokteran gigi. Risiko paling tinggi ditemukan pada penderita perokok dan peminum alkohol. Banyak tanaman herbal yang memiliki kandungan untuk menghambat pertumbuhan sel kanker

  17. From Leflunomide to Teriflunomide: Drug development and Immunosuppressive Oral Drugs in the Treatment of Multiple Sclerosis.

    Science.gov (United States)

    Aly, Lilian; Hemmer, Bernhard; Korn, Thomas

    2016-12-08

    Immunosuppressive drugs have been used in the treatment of multiple sclerosis (MS) for a long time. Today, the increased number of approved substances and the possibility of an oral availability of some immunomodulators improve the therapeutic repertory and increase patient satisfaction and compliance. Teriflunomide is indicated as first line oral disease modifying therapy (DMT) in relapsing-remitting MS (RRMS). Its immunosuppressive capacity results from an inhibition of de novo pyrimidine synthesis in rapidly proliferating lymphocytes. While Teriflunomide has been approved for the treatment of RRMS only since 2012, there is substantial therapeutic experience with its prodrug Leflunomide used in the treatment of rheumatoid arthritis (RA). In MS, a daily dose of 14 mg Teriflunomide reduces the annualized relapse rate (ARR) by more than 30% and disability progression by 30% compared to placebo while it provides a reasonable safety profile. This review presents an overview on oral immunosuppressants used in the treatment of MS. With an emphasis on Teriflunomide it summarizes discovery, mechanism of action and clinical effectiveness in phase II and III trials as well as important aspects for treating physicians.

  18. EDGE study in Russian Federation: efficacy and safety of vildagliptine in comparison with other oral antidiabetic agents in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    G R Galstyan

    2013-06-01

    Full Text Available According to international consensus, metformin is acknowledged as a first-line therapeutic agent for type 2 diabetes mellitus (T2DM. However, in most cases this treatment eventually requires intensification by supplementation with other hypoglycemic medications. The aim of the EDGE study (Effective Diabetes control with vildaGliptin and vildagliptin/mEtformin was to assess the efficacy and safety of vildagliptin in comparison with other oral agents in routine management of patients with T2DM that has been poorly controlled by metformin monotherapy.

  19. Antidiabetic therapy in real practice: indicators for adherence and treatment cost

    Directory of Open Access Journals (Sweden)

    Colombo GL

    2012-09-01

    Full Text Available Giorgio L Colombo,1,2 Elisa Rossi,4 Marisa De Rosa,4 Danilo Benedetto,3 Antonio V Gaddi31School of Pharmacy, Department of Drug Sciences, University of Pavia, Pavia, 2S.A.V.E. Studi Analisi Valutazioni Economiche, Milan, 3CINECA – Bologna; 4Centro Aterosclerosi GC Descovich, Dipartimento di Medicina Interna e dell'Invecchiamento, University of Bologna, Bologna, ItalyBackground: Type 2 diabetes has become a disease with a high economic and social impact. The ARNO Observatory is a clinical data warehouse consisting of a network of local health care units (ASL scattered throughout the Italian territory which collects data on health care consumption for about 10.5 million people. The purpose of this study was to evaluate the use of antidiabetic drugs with particular reference to type of treatment. The analyses were carried out on a sample of 169,375 patients treated with oral blood glucose-lowering drugs in 2008 from a total population of 4,040,624 health care beneficiaries at 12 local health care units in the ARNO Observatory.Methods: Patients were considered “on treatment with oral blood glucose-lowering drugs” if they had received at least one prescription of an antidiabetic drug (Anatomical Therapeutic Chemical code A10B during 2008. The patients were divided into three treatment groups, ie, monotherapy, fixed-combination drugs, and dual therapy. The following indicators were assessed: number of patients treated with an oral antidiabetic drug, mean number of hospitalizations, mean number of specialist examinations, and mean expenditure per treated patient. Adherence was assessed using the medication possession ratio indicator (MPR.Results: Patients treated with oral blood glucose-lowering drugs comprised 4.2% of the investigated population, and had an average age of 68.9 years. The mean annual number of hospitalizations was lower in the dual therapy group (298 versus 328 per 1000 patients in the sample, while the average number of

  20. Design Features of Drug-Drug Interaction Trials Between Antivirals and Oral Contraceptives.

    Science.gov (United States)

    Ayala, Ruben C; Arya, Vikram; Younis, Islam R

    2016-05-01

    The aim of this work was to explore the major design features of drug-drug interaction trials between antiviral medications (AVs) and oral contraceptives (OCs). Information on these trials (n = 27) was collected from approved drug labels and clinical pharmacology reviews conducted by the U.S. Food and Drug Administration. The primary objective of all trials was to evaluate changes in OC exposure following the coadministration of AVs. In addition, an evaluation of potential pharmacodynamic interaction was performed in 10 of these trials. Twenty-two trials were open label with a fixed-sequence design, and 5 trials used a double-blind crossover design. The trials were conducted using one, two, or three 28-day ovulatory cycles in 10, 8, and 9 trials, respectively. Only 1 trial enrolled HIV-infected women. The median number of women in a trial was 20 (range, 12 to 52). Norethindrone/ethinyl estradiol (EE) combination was the most commonly used OC (n = 16, 59%) followed by norgestimate/EE (n = 9, 33%). Labeling recommendations were based on exposure changes in 25 cases and on safety observations in the trial in 2 cases. In conclusion, a wide variety of trial designs was used, and there is no preferred design. The answer to the exposure question can be achieved using multiple designs.

  1. 21 CFR 328.50 - Principal display panel of all OTC drug products intended for oral ingestion that contain alcohol.

    Science.gov (United States)

    2010-04-01

    ... intended for oral ingestion that contain alcohol. 328.50 Section 328.50 Food and Drugs FOOD AND DRUG... PRODUCTS INTENDED FOR ORAL INGESTION THAT CONTAIN ALCOHOL Labeling § 328.50 Principal display panel of all OTC drug products intended for oral ingestion that contain alcohol. (a) The amount (percentage) of...

  2. Lipid-based formulations for oral administration of poorly water-soluble drugs

    DEFF Research Database (Denmark)

    Mu, Huiling; Holm, René; Müllertz, Anette

    2013-01-01

    Lipid-based drug delivery systems have shown great potentials in oral delivery of poorly water-soluble drugs, primarily for lipophilic drugs, with several successfully marketed products. Pre-dissolving drugs in lipids, surfactants, or mixtures of lipids and surfactants omits the dissolving....../dissolution step, which is a potential rate limiting factor for oral absorption of poorly water-soluble drugs. Lipids not only vary in structures and physiochemical properties, but also in their digestibility and absorption pathway; therefore selection of lipid excipients and dosage form has a pronounced effect...

  3. The rule of five for non-oral routes of drug delivery: ophthalmic, inhalation and transdermal.

    Science.gov (United States)

    Choy, Young Bin; Prausnitz, Mark R

    2011-05-01

    The Rule of Five predicts suitability of drug candidates, but was developed primarily using orally administered drugs. Here, we test whether the Rule of Five predicts drugs for delivery via non-oral routes, specifically ophthalmic, inhalation and transdermal. We assessed 111 drugs approved by FDA for those routes of administration and found that >98% of current non-oral drugs have physicochemical properties within the limits of the Rule of Five. However, given the inherent bias in the dataset, this analysis was not able to assess whether drugs with properties outside those limits are poor candidates. Indeed, further analysis indicates that drugs well outside the Rule of Five limits, including hydrophilic macromolecules, can be delivered by inhalation. In contrast, drugs currently administered across skin fall within more stringent limits than predicted by the Rule of Five, but new transdermal delivery technologies may make these constraints obsolete by dramatically increasing skin permeability. The Rule of Five does appear to apply well to ophthalmic delivery. We conclude that although current non-oral drugs mostly have physicochemical properties within the Rule of Five thresholds, the Rule of Five should not be used to predict non-oral drug candidates, especially for inhalation and transdermal routes.

  4. Recent advances in lipid nanoparticle formulations with solid matrix for oral drug delivery.

    Science.gov (United States)

    Das, Surajit; Chaudhury, Anumita

    2011-03-01

    Lipid nanoparticles based on solid matrix have emerged as potential drug carriers to improve gastrointestinal (GI) absorption and oral bioavailability of several drugs, especially lipophilic compounds. These formulations may also be used for sustained drug release. Solid lipid nanoparticle (SLN) and the newer generation lipid nanoparticle, nanostructured lipid carrier (NLC), have been studied for their capability as oral drug carriers. Biodegradable, biocompatible, and physiological lipids are generally used to prepare these nanoparticles. Hence, toxicity problems related with the polymeric nanoparticles can be minimized. Furthermore, stability of the formulations might increase than other liquid nano-carriers due to the solid matrix of these lipid nanoparticles. These nanoparticles can be produced by different formulation techniques. Scaling up of the production process from lab scale to industrial scale can be easily achieved. Reasonably high drug encapsulation efficiency of the nanoparticles was documented. Oral absorption and bioavailability of several drugs were improved after oral administration of the drug-loaded SLNs or NLCs. In this review, pros and cons, different formulation and characterization techniques, drug incorporation models, GI absorption and oral bioavailability enhancement mechanisms, stability and storage condition of the formulations, and recent advances in oral delivery of the lipid nanoparticles based on solid matrix will be discussed. © 2010 American Association of Pharmaceutical Scientists

  5. Lipid polymer hybrid as emerging tool in nanocarriers for oral drug delivery.

    Science.gov (United States)

    Hallan, Supandeep Singh; Kaur, Prabhjot; Kaur, Veerpal; Mishra, Neeraj; Vaidya, Bhuvaneshwar

    2016-01-01

    The oral route for drug delivery is a widely accepted route. For that reason, many researchers are currently working to develop efficient oral drug delivery systems. Use of polymeric nanoparticles (NPs) and lipid carrier systems, including liposomes, solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLC), has limitations such as drug leakage and high water content of dispersions. Thus, lipid polymer hybrid nanoparticles (LPNs) have been explored by the researchers to provide a better effect using properties of both polymers and lipids. The present review is focused on the challenges, possibilities, and future perspectives of LPNs for oral delivery.

  6. Insulin and longevity: antidiabetic biguanides as geroprotectors.

    Science.gov (United States)

    Anisimov, Vladimir N; Semenchenko, Anna V; Yashin, Anatoli I

    2003-01-01

    The results of previous experimental studies of effects of antidiabetic biguanides (phenformin and buformin) on life span and spontaneous tumor incidence in mice and rats were recalculated and reanalyzed using standard demographic models of mortality. The chronic treatment of female C3H/Sn mice with phenformin prolonged the mean life span by 21.1% (P biguanide, buformin, slightly increased their mean life span (by 7.3%; P > 0.05). The mean life span of the last 10% survivors increased by 12% (P biguanides slightly decreased the body weight, slowed down the age-related decline of the reproductive function in female rats. The results of our experiments provide evidence that antidiabetic biguanides are promising geroprotectors as well as drugs which can be used in the prevention of cancer.

  7. Physicochemical Properties of Solid Phospholipid Particles as a Drug Delivery Platform for Improving Oral Absorption of Poorly Soluble Drugs.

    Science.gov (United States)

    Kawakami, Kohsaku; Miyazaki, Aoi; Fukushima, Mayuko; Sato, Keiko; Yamamura, Yuko; Mohri, Kohta; Sakuma, Shinji

    2017-01-01

    A novel drug delivery platform, mesoporous phospholipid particle (MPP), is introduced. Its physicochemical properties and ability as a carrier for enhancing oral absorption of poorly soluble drugs are discussed. MPP was prepared through freeze-drying a cyclohexane/t-butyl alcohol solution of phosphatidylcholine. Its basic properties were revealed using scanning electron microscopy, x-ray diffraction, thermal analysis, hygroscopicity measurement, and so on. Fenofibrate was loaded to MPP as a poorly soluble model drug, and effect of MPP on the oral absorption behavior was observed. MPP is spherical in shape with a diameter typically in the range of 10-15 μm and a wide surface area that exceeds 10 m(2)/g. It has a bilayer structure that may accommodate hydrophobic drugs in the acyl chain region. When fenofibrate was loaded in MPP as a model drug, it existed partially in a crystalline state and improvement in the dissolution behavior was achieved in the presence of a surfactant, because of the formation of mixed micelles composed of phospholipids and surfactants in the dissolution media. MPP greatly improved the oral absorption of fenofibrate compared to that of the crystalline drug and its efficacy was almost equivalent to that of an amorphous drug dispersion. MPP is a promising option for improving the oral absorption of poorly soluble drugs based on the novel mechanism of dissolution improvement.

  8. Formulating a poorly water soluble drug into an oral solution suitable for paediatric patients; lorazepam as a model drug

    NARCIS (Netherlands)

    A.C. Van Der Vossen (Anna C.); I. Van Der Velde (Iris); O. Smeets (Oscar); Postma, D.J.; Eckhardt, M.; A. Vermes (Andras); B.C.P. Koch (Birgit C. P.); A.G. Vulto (Arnold); L.M. Hanff (Lidwien)

    2017-01-01

    textabstractIntroduction Many drugs are unavailable in suitable oral paediatric dosage forms, and pharmacists often have to compound drugs to provide paediatric patients with an acceptable formulation in the right dose. Liquid formulations offer the advantage of dosing flexibility and ease of admini

  9. Oral targeted therapies: managing drug interactions, enhancing adherence and optimizing medication safety in lymphoma patients.

    Science.gov (United States)

    Liewer, Susanne; Huddleston, Ashley N

    2015-04-01

    The advent of newer, targeted oral chemotherapy medications such as small molecule kinase inhibitors, ibrutinib and idelalisib, has created additional options for the treatment of lymphoma. The targeted nature of these agents offers many patient-identified advantages over older, intravenously administered chemotherapy regimens such as ease of self-administration and an increased sense of independence. However, newer oral agents also present unique challenges not previously experienced with older therapies that may affect safety, efficacy and patient adherence. In this article, we review oral agents for the treatment of lymphoma, how to evaluate and manage drug-drug and drug-food interactions with concomitant oral medications, and issues with patient adherence as well as methods to determine adherence for oral chemotherapy.

  10. Employment-Based Reinforcement of Adherence to Oral Naltrexone Treatment in Unemployed Injection Drug Users

    OpenAIRE

    Dunn, Kelly; DeFulio, Anthony; Everly, Jeffrey J.; Donlin, Wendy D.; Aklin, Will M.; Nuzzo, Paul A.; Leoutsakos, Jeannie-Marie S.; Umbricht, Annie; Fingerhood, Michael; Bigelow, George E.; Silverman, Kenneth

    2012-01-01

    Naltrexone has high potential for use as a relapse prevention pharmacotherapy for opiate dependence; however suffers from notoriously poor adherence when prescribed for oral self-administration. This study evaluated whether entry to a therapeutic workplace could be used to reinforce adherence with oral naltrexone. Opiate-dependent and cocaine-using injection drug users were detoxified, inducted onto oral naltrexone, and randomly assigned to a Contingency (n=35) or Prescription (n=32) group fo...

  11. An analytical evaluation of eight on-site oral fluid drug screening devices using laboratory confirmation results from oral fluid.

    NARCIS (Netherlands)

    Blencowe, T. Pehrsson, A. Lillsunde, P. Vimpari, K. Houwing, S. Smink, B. Mathijssen, R. Linden, T. van der Legrand, S.A. Pil, K. & Verstraete, A.

    2011-01-01

    The performance of eight on-site oral fluid drug screening devices was studied in Belgium, Finland and the Netherlands as a part of the EU-project DRUID. The main objective of the study was to evaluate the reliability of the devices for testing drivers suspected of driving under the influence of dru

  12. Engineered nanoparticulate drug delivery systems: the next frontier for oral administration?

    Science.gov (United States)

    Diab, Roudayna; Jaafar-Maalej, Chiraz; Fessi, Hatem; Maincent, Philippe

    2012-12-01

    For the past few decades, there has been a considerable research interest in the area of oral drug delivery using nanoparticle (NP) delivery systems as carriers. Oral NPs have been used as a physical approach to improve the solubility and the stability of active pharmaceutical ingredients (APIs) in the gastrointestinal juices, to enhance the intestinal permeability of drugs, to sustain and to control the release of encapsulated APIs allowing the dosing frequency to be reduced, and finally, to achieve both local and systemic drug targeting. Numerous materials have been used in the formulation of oral NPs leading to different nanoparticulate platforms. In this paper, we review various aspects of the formulation and the characterization of polymeric, lipid, and inorganic NPs. Special attention will be dedicated to their performance in the oral delivery of drug molecules and therapeutic genes.

  13. Early pharmaceutical profiling to predict oral drug absorption

    DEFF Research Database (Denmark)

    Bergström, Christel A S; Holm, René; Jørgensen, Søren Astrup

    2014-01-01

    Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmac......Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary...... and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties...

  14. Antidiabetic activity of Rheum emodi in Alloxan induced diabetic rats.

    Directory of Open Access Journals (Sweden)

    Radhika.R

    2010-09-01

    Full Text Available The present study was carried out to evaluate the antidiabetic effect of Rheum emodi rhizome extract and to study the activities of hexokinase, aldolase and phosphoglucoisomerase, and gluconeogenic enzymes such as glucose-6- phosphatase and fructose 1,6-diphosphatase in liver and kidney of normal and alloxan induced diabetic rats. Oral administration of 75 % ethanolic extract of R. emodi (250 mg/kg body weight for 30 days, resulted in decrease inthe activities of glucose-6-phosphatase, fructose-1,6-disphosphatase, aldolase and an increase in the activity of phosphoglucoisomerase and hexokinase in tissues. The study clearly shows that the R.emodi possesses antidiabetic activity.

  15. Antidiabetic and antioxidant activities of ethanolic extract of Semecarpus anacardium (Linn.) bark.

    Science.gov (United States)

    Ali, Md Ashraf; Wahed, Mir Imam Ibne; Khatune, Naznin Ara; Rahman, Bytul Mokaddesur; Barman, Ranjan Kumar; Islam, Md Rafiqul

    2015-04-29

    Diabetes mellitus is a global health problem and constantly increasing day by day. The number of diabetic people in world is expected to rise to 366 million in 2030. The available drugs for diabetes, insulin or oral hypoglycemic agents have one or more side effects and search for new antidiabetic drugs with minimal or no side effects from medicinal plants is a challenging for us. The present study was undertaken to investigate the antidiabetic and antioxidant activity of Semecarpus anacardium (Linn.) (abbreviated as SF). The antidiabetic activity was determined by using alloxan-induced diabetic rats. After 15 days of treatment, serum biochemical parameters such as TC, TG, LDL, HDL, SGOT and SGPT were estimated. The survival rate, body weight, organ weight, liver glycogen and blood parameters (RBC and Hb) were also measured. The antioxidant activity was measured by DPPH free radical scavenging assay. Phytochemical screening, total phenolic and total flavonoid content were determined by using standard methods. The results showed that the survival rate was 100% in rats of Group SA 400. The effect of extract on blood glucose level in Groups SA 100, SA 200 and SA 400 were dose-dependent throughout the treatment period. No significant changes in organ weight to body weight ratio were observed, liver weights significantly improved in Groups SA 200 and SA 400. The bark extract exhibited significant (p < 0.05) anti-diabetic activity with lowering TC, TG, LDL level dose-dependently and protected liver which may be partially explained by attenuation of SGOT and SGPT levels and increases liver glycogen. The percentage of Hb and RBC counts were negatively correlated with the doses of extracts. In DPPH scavenging assay, IC50 values of SA extract and ascorbic acid were found 72.24 μg/ml and 17.81 μg/ml, respectively. Phytochemical screening showed the presence of steroids, triterpenoids, flavonoids, glycosides, saponins, and tannins that were contribute to biological activity

  16. Effect of acidity of drugs on the prediction of human oral absorption by biopartitioning micellar chromatography

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Biopartitioning micellar chromatography(BMC)is a potentially high throughput and low cost alternative for in vitro prediction of drug absorption,which can mimic the drug partitioning process in biological systems.In this paper,a data set of 56 compounds representing acidic,basic,neutral and amphoteric drugs from various structure classes with human oral absorption(HOA)data available were employed to show the effect of acidity of drugs in oral absorption prediction.HOA was reciprocally correlated to the nega...

  17. [Novel oral anticancer drugs: a review of adverse drug reactions, interactions and patient adherence].

    Science.gov (United States)

    Bartal, Alexandra; Mátrai, Zoltán; Szucs, Attila; Belinszkaja, Galina; Langmár, Zoltán; Rosta, András

    2012-01-15

    Each aspect of oncological care is widely affected by the spread of oral anticancer agents, which raises several questions in terms of safe medication use and patient adherence. Over the past decade targeted therapies have appeared in clinical practice and revolutionized the pharmacological treatment of malignancies. Regular patient - doctor visits and proper patient education is crucial in order to comply with the therapy previously agreed upon with the oncologist, to increase patient adherence, to detect and to treat adverse effects in early stages. Since the information on the new medicines in Hungarian language is sparse it is the intention of the authors to give an overview of the basic knowledge, patient safety issues, adverse effects and interactions. Official drug information summaries and data on pharmacokinetics, interactions and adverse effects from the literature are reviewed as the basis for this overview.

  18. 5-FU Metabolism in Cancer and Orally-Administrable 5-FU Drugs

    Directory of Open Access Journals (Sweden)

    Iwao Sasaki

    2010-09-01

    Full Text Available 5-Fluorouracil (5-FU is a key anticancer drug that for its broad antitumor activity, as well as for its synergism with other anticancer drugs, has been used to treat various types of malignancies. In chemotherapeutic regimens, 5-FU has been combined with oxaliplatin, irinotecan and other drugs as a continuous intravenous infusion. Recent clinical chemotherapy studies have shown that several of the regimens with oral 5-FU drugs are not inferior compared to those involving continuous 5-FU infusion chemotherapy, and it is probable that in some regimens continuous 5-FU infusion can be replaced by oral 5-FU drugs. Historically, both the pharmaceutical industry and academia in Japan have been involved in the development of oral 5-FU drugs, and this review will focus on the current knowledge of 5-FU anabolism and catabolism, and the available information about the various orally-administrable 5-FU drugs, including UFT, S-1 and capecitabine. Clinical studies comparing the efficacy and adverse events of S-1 and capecitabine have been reported, and the accumulated results should be utilized to optimize the treatment of cancer patients. On the other hand, it is essential to elucidate the pharmacokinetic mechanism of each of the newly-developed drugs, to correctly select the drugs for each patient in the clinical setting, and to further develop optimized drug derivatives.

  19. pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms.

    Science.gov (United States)

    Liu, Lin; Yao, WenDong; Rao, YueFeng; Lu, XiaoYang; Gao, JianQing

    2017-11-01

    Oral administration is a desirable alternative of parenteral administration due to the convenience and increased compliance to patients, especially for chronic diseases that require frequent administration. The oral drug delivery is a dynamic research field despite the numerous challenges limiting their effective delivery, such as enzyme degradation, hydrolysis and low permeability of intestinal epithelium in the gastrointestinal (GI) tract. pH-Responsive carriers offer excellent potential as oral therapeutic systems due to enhancing the stability of drug delivery in stomach and achieving controlled release in intestines. This review provides a wide perspective on current status of pH-responsive oral drug delivery systems prepared mainly with organic polymers or inorganic materials, including the strategies used to overcome GI barriers, the challenges in their development and future prospects, with focus on technology trends to improve the bioavailability of orally delivered drugs, the mechanisms of drug release from pH-responsive oral formulations, and their application for drug delivery, such as protein and peptide therapeutics, vaccination, inflammatory bowel disease (IBD) and bacterial infections.

  20. Addressing Unmet Medical Needs in Type 2 Diabetes: A Narrative Review of Drugs under Development

    OpenAIRE

    Mittermayer, Friedrich; Caveney, Erica; Oliveira,Claudia de; Gourgiotis, Loukas; Puri, Mala; Tai, Li-Jung (Bruce); J, Rick Turner

    2015-01-01

    The global burden of type 2 diabetes is increasing worldwide, and successful treatment of this disease needs constant provision of new drugs. Twelve classes of antidiabetic drugs are currently available, and many new drugs are under clinical development. These include compounds with known mechanisms of action but unique properties, such as once-weekly DPP4 inhibitors or oral insulin. They also include drugs with new mechanisms of action, the focus of this review. Most of these compounds are i...

  1. Lichenoid Drug Eruptionfollowing Intravenous Applicationof Orally Formulated Diamorphine, a Semisynthetic Heroin

    Directory of Open Access Journals (Sweden)

    I. Kolm

    2013-06-01

    Full Text Available Background: Lichen planus is a common skin disorder of unknown etiology. Most cases are idiopathic, but substances such as gold, antimalarials, penicillamine, thiazide diuretics, β-blockers, arsenic and nonsteroidal anti-inflammatory drugs have been implicated as trigger factors. Case Presentation: We report the case of a lichenoid eruption in a male drug addict who administered oral heroin (diamorphine intravenously. Diamorphine was stopped immediately. Following topical steroids, phototherapy and oral acitretin, the lesions gradually disappeared. A lymphocyte transformation test was negative for pure morphine and codeine. Discussion: A coincidental association between the intravenous application of orally formulated semisynthetic heroin and the lichenoid eruption cannot be completely ruled out. However, the diagnosis of a lichenoid drug eruption is favoured over idiopathic lichen planus because of the clear chronological correlation between drug use and appearance as well as drug withdrawal and disappearance of the skin lesions, and because of a flare-up following repeated intravenous application of diamorphine.

  2. Antidiabetic Effects of Aqueous Infusions of Artemisia herba-alba and Ajuga iva in Alloxan-Induced Diabetic Rats.

    Science.gov (United States)

    Boudjelal, Amel; Siracusa, Laura; Henchiri, Cherifa; Sarri, Madani; Abderrahim, Benkhaled; Baali, Faiza; Ruberto, Giuseppe

    2015-06-01

    The aqueous infusions of the aerial parts of Artemisia herba-alba Asso and Ajuga iva Schreber, prepared in accordance with the traditional procedure used in the local folk medicine, have been analysed for their composition and content of phytochemical constituents and examined for their antidiabetic effectiveness in alloxan-induced diabetic rats. Oral administration of A. herba-alba and A. iva infusions was studied in normal and alloxan-induced diabetic rats, which were randomly divided into nine groups, each group consisting of six animals. The drug preparations (100, 200, and 300 mg/kg b. w.) of each plant were given orally to the rats of each group twice daily for 15 days. Compositional analysis of the aqueous infusions revealed the presence of several polyphenols as main components. A. herba-alba infusion was characterised by mono- and di-cinnamoylquinic acids, with 5-caffeoylquinic (chlorogenic) acid being the main compound, followed by 3,5-dicaffeoylquinic acid. Vicenin-2 (apigenin 6,8-di-C-glucoside) appeared to be the most abundant among flavonoids. On the other hand, A. iva showed the exclusive presence of flavonoids, with the flavanone naringin present in relatively high levels together with several apigenin (flavone) derivatives. Oral administration of 300 mg/kg b. w. of the aqueous infusions of A. herba-alba and A. iva exhibited a significant reduction in blood glucose content, showing a much more efficient antidiabetic activity compared to glibenclamide, the oral hypoglycaemic agent used as a positive control in this study. These results suggest that A. herba-alba and A. iva possess significant antidiabetic activity, as they were able to improve the biochemical damage in alloxan-induced diabetes in rats. Georg Thieme Verlag KG Stuttgart · New York.

  3. Encapsulation of Liposomes within pH Responsive Microspheres for Oral Colonic Drug Delivery

    Directory of Open Access Journals (Sweden)

    M. J. Barea

    2012-01-01

    Full Text Available A novel liposome-in-microsphere (LIM formulation has been created comprising drug-loaded liposomes within pH responsive Eudragit S100 microspheres. The liposomes contained the model drug 5-ASA and were coated with chitosan in order to protect them during encapsulation within the microspheres and to improve site-specific release characteristics. In vitro drug release studies showed that LIMs prevented drug release within simulated stomach and small intestine conditions with subsequent drug release occurring in large intestine conditions. The formulation therefore has potential for oral colonic drug delivery.

  4. SELF EMULSIFYING DRUG DELIVERY SYSTEM: A CONVENTIONAL AND ALTERNATIVE APPPROACH TO IMPROVE ORAL BIOAVAILABILITY OF LIPOPHILIC DRUGS

    Directory of Open Access Journals (Sweden)

    Desai Tushar R

    2010-12-01

    Full Text Available Out of newly discovered drugs most of the drugs are found to be lipophilic and out of which up to 40 % of pharmacologically active new molecules failed to reach to market only due to little or no water solubility; a serious challenge for the successful development and commercialization of new drugs in the pharmaceutica lindustry. Therefore various formulation strategies have been investigated to improve the solubility and the rate of dissolut ion to enhance the oral bioavailability of lipophilic drugs. Amongst various approach self emulsifying drug delivery system has gained more attention due to enhanced oral bio-availability enabling reduction in dose, more consistent temporal profiles of drug absorption, selective targeting of drug(s toward specific absorption window in GIT, and protection of drug(s from the hostile environment in gut. The present review discussed the mechanisam of self emulsification, composition, formulation approaches, different techniques, evaluation, factors affecting SEDDS, advantages, draw backs, applications and future trends in SEDDS.

  5. Development of polyherbal antidiabetic formulation encapsulated in the phospholipids vesicle system

    Directory of Open Access Journals (Sweden)

    Vinod Kumar Gauttam

    2013-01-01

    Full Text Available Multifactorial metabolic diseases, for instance diabetes develop several complications like hyperlipidemia, hepatic toxicity, immunodeficiency etc., Hence, instead of mono-drug therapy the management of the disease requires the combination of herbs. Marketed herbal drugs comprise of irrational combinations, which makes their quality control more difficult. Phytoconstituents, despite having excellent bioactivity in vitro demonstrate less or no in vivo actions due to their poor lipid solubility, resulting in high therapeutic dose regimen; phospholipids encapsulation can overcome this problem. Hence, present study was designed to develop a phospholipids encapsulated polyherbal anti-diabetic formulation. In the present study, polyherbal formulation comprises of lyophilized hydro-alcoholic (50% v/v extracts of Momordica charantia, Trigonella foenum-graecum and Withania somnifera 2:2:1, respectively, named HA, optimized based on oral glucose tolerance test model in normal Wistar rats. The optimized formulation (HA entrapped in the phosphatidylcholine and cholesterol (8:2 vesicle system is named HA lipids (HAL. The vesicles were characterized for shape, morphology, entrapment efficiency, polar-dispersity index and release profile in the gastric pH. The antidiabetic potential of HA, marketed polyherbal formulation (D-fit and HAL was compared in streptozotocin-induced diabetic rat model of 21 days study. The parameters evaluated were behavioral changes, body weight, serum glucose level, lipid profile and oxidative stress. The antidiabetic potential of HA (1000 mg/kg was at par with the D-fit (1000 mg/kg. However, the potential was enhanced by phospholipids encapsulation; as HAL (500 mg/kg has shown more significant (P < 0.05 potential in comparison to HA (1000 mg/kg and at par with metformin (500 mg/kg.

  6. 77 FR 28252 - Oral Dosage Form New Animal Drugs; Change of Sponsor; Griseofulvin Powder; Levamisole...

    Science.gov (United States)

    2012-05-14

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Change of.... Joseph, MO 64503, has informed FDA that it has transferred ownership of, and all rights and interest in... current format. This rule does not meet the definition of ``rule'' in 5 U.S.C. 804(3)(A) because it is a...

  7. 78 FR 57057 - Oral Dosage Form New Animal Drugs; Amprolium; Meloxicam

    Science.gov (United States)

    2013-09-17

    ...; Meloxicam AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug........... Ceva Sante MELOXIDYL Original approval 520.1350 Yes....... CE \\1\\. Animale, 10 (meloxicam) Oral as a....1367 Meloxicam. (a) Specifications--(1) Each milliliter of suspension contains 0.5 milligrams...

  8. Self-Micro Emulsifying Drug Delivery Systems: a Strategy to Improve Oral Bioavailability

    Directory of Open Access Journals (Sweden)

    Vijay K. Sharma

    Full Text Available Aim: Oral route has always been the favorite route of drug administration in many diseases and till today it is the first way investigated in the development of new dosage forms. The major problem in oral drug formulations is low and erratic bioavailability, which mainly results from poor aqueous solubility, thereby pose problems in their formulation. For the therapeutic delivery of lipophilic active moieties (BCS class II drugs, lipid based formulations are inviting increasing attention. Methods: To that aim, from the web sites of PubMed, HCAplus, Thomson, and Registry were used as the main sources to perform the search for the most significant research articles published on the subject. The information was then carefully analyzed, highlighting the most important results in the formulation and development of self-micro emulsifying drug delivery systems as well as its therapeutic activity. Results: Self-emulsifying drug delivery system (SMEDDS has gained more attention due to enhanced oral bio-availability enabling reduction in dose, more consistent temporal profiles of drug absorption, selective targeting of drug(s toward specific absorption window in GIT, and protection of drug(s from the unreceptive environment in gut. Conclusions: This article gives a complete overview of SMEDDS as a promising approach to effectively deal with the problem of poorly soluble molecules.

  9. Pectin matrix as oral drug delivery vehicle for colon cancer treatment.

    Science.gov (United States)

    Wong, Tin Wui; Colombo, Gaia; Sonvico, Fabio

    2011-03-01

    Colon cancer is the fourth most common cancer globally with 639,000 deaths reported annually. Typical chemotherapy is provided by injection route to reduce tumor growth and metastasis. Recent research investigates the oral delivery profiles of chemotherapeutic agents. In comparison to injection, oral administration of drugs in the form of a colon-specific delivery system is expected to increase drug bioavailability at target site, reduce drug dose and systemic adverse effects. Pectin is suitable for use as colon-specific drug delivery vehicle as it is selectively digested by colonic microflora to release drug with minimal degradation in upper gastrointestinal tract. The present review examines the physicochemical attributes of formulation needed to retard drug release of pectin matrix prior to its arrival at colon, and evaluate the therapeutic value of pectin matrix in association with colon cancer. The review suggests that multi-particulate calcium pectinate matrix is an ideal carrier to orally deliver drugs for site-specific treatment of colon cancer as (1) crosslinking of pectin by calcium ions in a matrix negates drug release in upper gastrointestinal tract, (2) multi-particulate carrier has a slower transit and a higher contact time for drug action in colon than single-unit dosage form, and (3) both pectin and calcium have an indication to reduce the severity of colon cancer from the implication of diet and molecular biology studies. Pectin matrix demonstrates dual advantages as drug carrier and therapeutic for use in treatment of colon cancer.

  10. Synthesis and Antidiabetic Evaluation of Benzothiazole Derivatives

    Energy Technology Data Exchange (ETDEWEB)

    G, Mariappan; P, Prabhat; L, Sutharson; J, Banerjee; U, Patangia; S, Nath [Himalayan Pharmacy Institute, Majhitar (India)

    2012-04-15

    A novel series of benzothiazole derivatives were synthesized and assayed in vivo to investigate their hypogly-cemic activity by streptozotocin-induced diebetic model in rat. These derivatives showed considerable biological efficacy when compared to glibenclamide, a potent and well known antidiabetic agent as a reference drug. All the compounds were effective, amongst them 3d showed more prominent activity at 100 mg/kg p.o. The experimental results are statistically significant at p<0.01 and p<0.05 level.

  11. Antidiabetic Activity of Polyherbal Formulation in Streptozotocin – Nicotinamide Induced Diabetic Wistar Rats

    Science.gov (United States)

    Petchi, Rajendran Ramesh; Vijaya, Chockalingam; Parasuraman, Subramani

    2014-01-01

    Glycosmis pentaphylla, Tridax procumbens, and Mangifera indica are well-known plants available throughout India and they are commonly used for the treatment of various diseases including diabetes mellitus. The antidiabetic activity of the individual plant parts is well known, but the synergistic or combined effects are unclear. The concept of polyherbalism has been highlighted in Sharangdhar Samhita, an Ayurvedic literature dating back to 1300 AD. Polyherbal formulations enhance the therapeutic action and reduce the concentrations of single herbs, thereby reducing adverse events. The aim of the present study is to formulate a polyherbal formulation and evaluate its antidiabetic potential in animals. The polyherbal formulation was formulated using the ethanol extracts of the stem bark of G. pentaphylla, whole plant of T. procumbens, and leaves of M. indica. The polyherbal formulation contains the ethanol extracts of G. pentaphylla, T. procumbens, and M. indica in the ratio of 2:2:1. The quality of the finished product was evaluated as per the World Health Organization's guidelines for the quality control of herbal materials. The quality testing parameters of the polyherbal formulation were within the limits. Fingerprint analysis of the polyherbal formulation showed effective separation at 366 nm, and it revealed that the active compound present in the polyherbal formulation and the active compounds present in all the three extracts were the same. The acute toxicity studies of the polyherbal formulation did not show any toxic symptoms in doses up to 2000 mg/kg over 14 days. The oral antidiabetic activity of the polyherbal formulation (250 and 500 mg/kg) was screened against streptozotocin (50 mg/kg; i.p.) + nicotinamide (120 mg/kg; i.p.) induced diabetes mellitus in rats. The investigational drug was administered for 21 consecutive days, and the effect of the polyherbal formulation on blood glucose levels was studied at regular intervals. At the end of the study, the

  12. Antidiabetic activity of aqueous root extract ofMerremia tridentata (L.) Hall. f. in streptozotocin-induced-diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Karuppusamy Arunachalam; Thangaraj Parimelazhagan

    2012-01-01

    Objective:To investigate the antidiabetic effect of aqueous extract ofMerremia tridentata (M. tridentata) root(MTRAE) in normal, glucose-loaded hyperglycemic and streptozotocin (STZ)-induced diabetic rats.Methods: Oral administration ofMTRAE at the doses of50, 100 and150 mg/kg was studied in normal, glucose-loaded andSTZ-diabetic rats. The three doses caused significant reduction in blood glucose levels in all the models.Results: The effect was more pronounced in100and150mg/kg than50 mg/kg.MTRAE also showed significant increase in serum insulin, body weight and glycogen content in liver and skeletal muscle ofSTZ-induced diabetic rats while there was significant reduction in the levels of serum triglyceride and total cholesterol.MTRAE also showed significant antilipidperoxidative effect in the pancreas ofSTZ-induced diabetic rats. The antidiabetic effect ofM. tridentata was compared with glibenclamide, a well known hypoglycemic drug.Conclusions:The results indicate that aqueous extract ofM. tridentata root possesses significant antidiabetic activity.

  13. Studies on the Antidiabetic Activities of Cordyceps militaris Extract in Diet-Streptozotocin-Induced Diabetic Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Yuan Dong

    2014-01-01

    Full Text Available Due to substantial morbidity and high complications, diabetes mellitus is considered as the third “killer” in the world. A search for alternative antidiabetic drugs from herbs or fungi is highly demanded. Our present study aims to investigate the antidiabetic activities of Cordyceps militaris on diet-streptozotocin-induced type 2 diabetes mellitus in rats. Diabetic rats were orally administered with water extract or alcohol extract at 0.05 g/kg and 2 g/kg for 3 weeks, and then, the factors levels related to blood glucose, lipid, free radicals, and even nephropathy were determined. Pathological alterations on liver and kidney were examined. Data showed that, similar to metformin, Cordyceps militaris extracts displayed a significant reduction in blood glucose levels by promoting glucose metabolism and strongly suppressed total cholesterol and triglycerides concentration in serum. Cordyceps militaris extracts exhibit antioxidative effects indicated by normalized superoxide dismutase and glutathione peroxidase levels. The inhibitory effects on blood urea nitrogen, creatinine, uric acid, and protein revealed the protection of Cordyceps militaris extracts against diabetic nephropathy, which was confirmed by pathological morphology reversion. Collectively, Cordyceps militaris extract, a safe pharmaceutical agent, presents excellent antidiabetic and antinephropathic activities and thus has great potential as a new source for diabetes treatment.

  14. Studies on the Antidiabetic Activities of Cordyceps militaris Extract in Diet-Streptozotocin-Induced Diabetic Sprague-Dawley Rats

    Science.gov (United States)

    Dong, Yuan; Jing, Tianjiao; Meng, Qingfan; Liu, Chungang; Hu, Shuang; Ma, Yihang; Liu, Yan; Lu, Jiahui; Cheng, Yingkun; Teng, Lirong

    2014-01-01

    Due to substantial morbidity and high complications, diabetes mellitus is considered as the third “killer” in the world. A search for alternative antidiabetic drugs from herbs or fungi is highly demanded. Our present study aims to investigate the antidiabetic activities of Cordyceps militaris on diet-streptozotocin-induced type 2 diabetes mellitus in rats. Diabetic rats were orally administered with water extract or alcohol extract at 0.05 g/kg and 2 g/kg for 3 weeks, and then, the factors levels related to blood glucose, lipid, free radicals, and even nephropathy were determined. Pathological alterations on liver and kidney were examined. Data showed that, similar to metformin, Cordyceps militaris extracts displayed a significant reduction in blood glucose levels by promoting glucose metabolism and strongly suppressed total cholesterol and triglycerides concentration in serum. Cordyceps militaris extracts exhibit antioxidative effects indicated by normalized superoxide dismutase and glutathione peroxidase levels. The inhibitory effects on blood urea nitrogen, creatinine, uric acid, and protein revealed the protection of Cordyceps militaris extracts against diabetic nephropathy, which was confirmed by pathological morphology reversion. Collectively, Cordyceps militaris extract, a safe pharmaceutical agent, presents excellent antidiabetic and antinephropathic activities and thus has great potential as a new source for diabetes treatment. PMID:24738047

  15. A Novel Multilayered Multidisk Oral Tablet for Chronotherapeutic Drug Delivery

    Directory of Open Access Journals (Sweden)

    Zaheeda Khan

    2013-01-01

    Full Text Available A Multilayered Multidisk Tablet (MLMDT comprising two drug-loaded disks enveloped by three drug-free barrier layers was developed for use in chronotherapeutic disorders, employing two model drugs, theophylline and diltiazem HCl. The MLMDT was designed to achieve two pulses of drug release separated by a lag phase. The polymer disk comprised hydroxyethylcellulose (HEC and ethylcellulose (EC granulated using an aqueous dispersion of EC. The polymeric barrier layers constituted a combination of pectin/Avicel (PBL (1st barrier layer and hydroxypropylmethylcellulose (HPMC (HBL1 and HBL2 as the 2nd and 3rd barrier layers, respectively. Sodium bicarbonate was incorporated into the diltiazem-containing formulation for delayed drug release. Erosion and swelling studies confirmed the manner in which the drug was released with theophylline formulations exhibiting a maximum swelling of 97% and diltiazem containing formulations with a maximum swelling of 119%. FTIR spectra displayed no interactions between drugs and polymers. Molecular mechanics simulations were undertaken to predict the possible orientation of the polymer morphologies most likely affecting the MLMDT performance. The MLMDT provided two pulses of drug release, separated by a lag phase, and additionally it displayed desirable friability, hardness, and uniformity of mass indicating a stable formulation that may be a desirable candidate for chronotherapeutic drug delivery.

  16. CONTEMPORARY APPROACHES FOR BI-LAYER TECHNOLOGY OF DRUGS THROUGH ORAL ROUTE: AN OVERVIEW

    Directory of Open Access Journals (Sweden)

    Rishikesh*, M. A. Bhuiyan, S. M. Ashraful Islam, I. Dewan, Md. A. Islam and Md. S.- Ul H. Miah

    2013-04-01

    Full Text Available ABSTRACT: Bi-layer tablet technology for bimodal release of drug and co-administration of drugs via oral route has been engaged a significant place in the field of drug delivery technology. At present, several pharmaceutical companies are developing bilayer tablet for co-administration of drugs to improve the therapeutic efficacy as well as to reduce the chances of drug-drug interaction. This review indicates the different aspects of drug release mechanism, different strategies of drug release, various techniques for bilayer tablet, and the influence of different process and formulation parameters must be considered during the development of bilayer tablet. Bi-layer tablet is suitable for sequential release of two drugs in combination, separate two incompatible substances, and also for sustained release tablet in which one layer is immediate release as initial dose and second layer is maintenance dose.

  17. Preparation of multiparticulate systems for oral delivery of a micronized or nanosized poorly soluble drug.

    Science.gov (United States)

    Cerea, Matteo; Pattarino, Franco; Foglio Bonda, Andrea; Palugan, Luca; Segale, Lorena; Vecchio, Carlo

    2016-09-01

    The purpose of the present work was to prepare multiparticulate drug delivery systems for oral administration of a poorly soluble drug such as itraconazole. Multiparticulate systems were prepared by extrusion/spheronization technique using a mix of crospovidone, low viscosity hypromellose, microcrystalline cellulose, micronized drug and water. In order to improve the release performance of the multiparticulate systems, the micronized drug was suspended in water with polysorbate 20 and nanonized by a high-pressure homogenization. The suspension of drug nanoparticles was then spray-dried for enabling an easy handling of the drug and for preventing the over-wetting of the powders during extrusion/spheronization processing. Both multiparticulate units prepared with micronized or nanonized drug showed acceptable disintegrating properties. The nanosizing of micronized drug powder provided a significant improvement of drug dissolution rates of the multiparticulates.

  18. Role of nanoparticle size, shape and surface chemistry in oral drug delivery.

    Science.gov (United States)

    Banerjee, Amrita; Qi, Jianping; Gogoi, Rohan; Wong, Jessica; Mitragotri, Samir

    2016-09-28

    Nanoparticles find intriguing applications in oral drug delivery since they present a large surface area for interactions with the gastrointestinal tract and can be modified in various ways to address the barriers associated with oral delivery. The size, shape and surface chemistry of nanoparticles can greatly impact cellular uptake and efficacy of the treatment. However, the interplay between particle size, shape and surface chemistry has not been well investigated especially for oral drug delivery. To this end, we prepared sphere-, rod- and disc-shaped nanoparticles and conjugated them with targeting ligands to study the influence of size, shape and surface chemistry on their uptake and transport across intestinal cells. A triple co-culture model of intestinal cells was utilized to more closely mimic the intestinal epithelium. Results demonstrated higher cellular uptake of rod-shaped nanoparticles in the co-culture compared to spheres regardless of the presence of active targeting moieties. Transport of nanorods across the intestinal co-culture was also significantly higher than spheres. The findings indicate that nanoparticle-mediated oral drug delivery can be potentially improved with departure from spherical shape which has been traditionally utilized for the design of nanoparticles. We believe that understanding the role of nanoparticle geometry in intestinal uptake and transport will bring forth a paradigm shift in nanoparticle engineering for oral delivery and non-spherical nanoparticles should be further investigated and considered for oral delivery of therapeutic drugs and diagnostic materials.

  19. Drug: D00625 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ose metabolism hsa04973(8972) Carbohydrate digestion and absorption map07051 Antidiabetics Therapeutic categ...ory of drugs in Japan [BR:br08301] 3 Agents affecting metabolism 39 Other agents affecting metabolism 396 Antidiabetic...Miglitol (JAN/USAN/INN) USP drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic

  20. The Relation of Changes in Prescribing Patterns of Anti-diabetic Drugs and HbA1c Levels Among Patients with Type 2 Diabetes Mellitus: Systematic Analysis of Studies From the the Past 20 Years in Turkey

    Directory of Open Access Journals (Sweden)

    Hasan İlkova

    2011-12-01

    48.4% to 32.9%. Most of patients (60.5±10.8% included in the analysis were identified to receive ongoing oral anti-diabetic (OAD treatment followed by insulin (17.1%±12.5%, diet (14.3%±14.4% and OAD+insulin (9.2%±10.5%. In conclusion, analysis of a total of 26.898 patients with type 2 DM in the present review revealed a positive change mainly towards a better glycemic control and comparatively lower risk of diabetes-related complication , by means of substantial increase in use of analogue insulin as well as introduction of novel glitazones from 1990-1999 to 2000-2008 in Turkey. Turk Jem 2011; 15: 77-105

  1. Personalised treatment with oral anticoagulant drugs : clinical and economic issues

    NARCIS (Netherlands)

    Verhoef, T.I.

    2013-01-01

    Coumarin derivatives such as acenocoumarol, phenprocoumon and warfarin are frequently used for the prevention of stroke and systemic embolism in patients with atrial fibrillation or for the treatment of venous thromboembolism. These oral anticoagulants have a narrow therapeutic range and a large var

  2. Challenges in oral drug delivery in patients with esophageal dysphagia

    NARCIS (Netherlands)

    Kappelle, W.F.; Siersema, P.D.; Bogte, A.; Vleggaar, F.P.

    2016-01-01

    INTRODUCTION: Esophageal dysphagia is a commonly reported symptom with various benign and malignant causes. Esophageal dysphagia can impede intake of oral medication, which often poses a major challenge for both patients and physicians. The best way to address this challenge depends of the cause of

  3. 76 FR 25696 - Guidance for Industry on Dosage Delivery Devices for Orally Ingested OTC Liquid Drug Products...

    Science.gov (United States)

    2011-05-05

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Dosage Delivery Devices for Orally... entitled ``Dosage Delivery Devices for Orally Ingested OTC Liquid Drug Products.'' This document is... over-the-counter (OTC) liquid drug products packaged with dosage delivery devices (e.g.,...

  4. Bioequivalence study designs for generic solid oral anticancer drug products: scientific and regulatory considerations.

    Science.gov (United States)

    Kaur, Paramjeet; Chaurasia, Chandra S; Davit, Barbara M; Conner, Dale P

    2013-12-01

    The demonstration of bioequivalence (BE) between the test and reference products is an integral part of generic drug approval process. A sound BE study design is pivotal to the successful demonstration of BE of generic drugs to their corresponding reference listed drug product. Generally, BE of systemically acting oral dosage forms is demonstrated in a crossover, single-dose in vivo study in healthy subjects. The determination of BE of solid oral anticancer drug products is associated with its own unique challenges due to the serious safety risks involved. Unlike typical BE study in healthy subjects, the safety issues often necessitate conducting BE studies in cancer patients. Such BE studies of an anticancer drug should be conducted without disturbing the patients' therapeutic dosing regimen. Attributes such as drug permeability and solubility, pharmacokinetics, dosing regimen, and approved therapeutic indication(s) are considered in the BE study design of solid anticancer drug products. To streamline the drug approval process, the Division of Bioequivalence posts the Bioequivalence Recommendations for Specific Products guidances on the FDA public website. The objective of this article is to illustrate the scientific and regulatory considerations in the design of BE studies for generic solid oral anticancer drug products through examples.

  5. Rationalizing the selection of oral lipid based drug delivery systems by an in vitro dynamic lipolysis model for improved oral bioavailability of poorly water soluble drugs.

    Science.gov (United States)

    Dahan, Arik; Hoffman, Amnon

    2008-07-02

    As a consequence of modern drug discovery techniques, there has been a consistent increase in the number of new pharmacologically active lipophilic compounds that are poorly water soluble. A great challenge facing the pharmaceutical scientist is making these molecules into orally administered medications with sufficient bioavailability. One of the most popular approaches to improve the oral bioavailability of these molecules is the utilization of a lipid based drug delivery system. Unfortunately, current development strategies in the area of lipid based delivery systems are mostly empirical. Hence, there is a need for a simplified in vitro method to guide the selection of a suitable lipidic vehicle composition and to rationalize the delivery system design. To address this need, a dynamic in vitro lipolysis model, which provides a very good simulation of the in vivo lipid digestion process, has been developed over the past few years. This model has been extensively used for in vitro assessment of different lipid based delivery systems, leading to enhanced understanding of the suitability of different lipids and surfactants as a delivery system for a given poorly water soluble drug candidate. A key goal in the development of the dynamic in vitro lipolysis model has been correlating the in vitro data of various drug-lipidic delivery system combinations to the resultant in vivo drug profile. In this paper, we discuss and review the need for this model, its underlying theory, practice and limitations, and the available data accumulated in the literature. Overall, the dynamic in vitro lipolysis model seems to provide highly useful initial guidelines in the development process of oral lipid based drug delivery systems for poorly water soluble drugs, and it predicts phenomena that occur in the pre-enterocyte stages of the intestinal absorption cascade.

  6. Drug: D08996 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available nhibitor [HSA:1803] [KO:K01278] hsa04974(1803) Protein digestion and absorption Transporter: ABCB1 [HSA:5243] map07051 Antidiabetic...P drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic Agents S

  7. Drug: D09753 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Protein digestion and absorption map07051 Antidiabetics Therapeutic category of d...rugs in Japan [BR:br08301] 3 Agents affecting metabolism 39 Other agents affecting metabolism 396 Antidiabetic

  8. Recent developments in oral lipid-based drug delivery

    DEFF Research Database (Denmark)

    Thomas, N.; Rades, T.; Müllertz, A.

    2013-01-01

    and characterization of LbDDS. In particular, the lack of standardized test protocols can be identified as the major obstacles for the broader application of LbDDS. This review seeks to summarize recent approaches in the field of lipid-based drug delivery that try to elucidate some critical steps in their development......The increasing number of poorly water-soluble drugs in development in the pharmaceutical industry has sparked interest in novel drug delivery options such as lipid-based drug delivery systems (LbDDS). Several LbDDS have been marketed successfully and have shown superior and more reliable...... bioavailability compared to conventional formulations. However, some reluctance in the broader application of LbDDS still appears, despite the growing commercial interest in lipids as a drug delivery platform. This reluctance might at least in part be related to the complexity associated with the development...

  9. The use of hypromellose in oral drug delivery.

    Science.gov (United States)

    Li, Chi L; Martini, Luigi G; Ford, James L; Roberts, Matthew

    2005-05-01

    Hypromellose, formerly known as hydroxypropylmethylcellulose (HPMC), is by far the most commonly employed cellulose ether used in the fabrication of hydrophilic matrices. Hypromellose provides the release of a drug in a controlled manner, effectively increasing the duration of release of a drug to prolong its therapeutic effect. This review provides a current insight into hypromellose and its applicability to hydrophilic matrices in order to highlight the basic parameters that affect its performance. Topics covered include the chemical, thermal and mechanical properties of hypromellose, hydration of the polymer matrices, the mechanism of drug release and the influence of tablet geometry on drug-release rate. The inclusion of drug-release modifiers within hypromellose matrices, the effects of dissolution media and the influence of both the external environment and microenvironment pH within the gel matrix on the properties of the polymer are also discussed.

  10. Recent developments in oral lipid-based drug delivery

    DEFF Research Database (Denmark)

    Thomas, N.; Rades, T.; Müllertz, A.

    2013-01-01

    The increasing number of poorly water-soluble drugs in development in the pharmaceutical industry has sparked interest in novel drug delivery options such as lipid-based drug delivery systems (LbDDS). Several LbDDS have been marketed successfully and have shown superior and more reliable...... bioavailability compared to conventional formulations. However, some reluctance in the broader application of LbDDS still appears, despite the growing commercial interest in lipids as a drug delivery platform. This reluctance might at least in part be related to the complexity associated with the development...... and characterization of LbDDS. In particular, the lack of standardized test protocols can be identified as the major obstacles for the broader application of LbDDS. This review seeks to summarize recent approaches in the field of lipid-based drug delivery that try to elucidate some critical steps in their development...

  11. The safety and effectiveness of once daily detemir in patients with type 2 diabetes previously failing oral agents:the Chinese cohort from SOL-VETM observational study

    Institute of Scientific and Technical Information of China (English)

    潘长玉

    2013-01-01

    Objective To evaluate the safety and effectiveness of initiating once-daily insulin detemir(Levemir) as add-on therapy in patients with type 2 diabetes mellitus(T2DM) who failed treatment of oral anti-diabetic drugs(OAD).Methods The present study was derived from the data of

  12. Design, synthesis and antidiabetic evaluation of oxazolone derivatives

    Indian Academy of Sciences (India)

    G Mariappan; B P Saha; Sriparna Datta; Deepak Kumar; P K Haldar

    2011-05-01

    A series of ten novel (2a-j) 4-arylidine 2-[4-methoxy phenyl] oxazol-5-one derivatives were synthesized and assayed in vivo to investigate their antidiabetic activities by streptozotocin-induced model in rat. These derivatives showed considerable biological efficacy when compared to rosiglitazone, a potent and wellknown antidiabetic agent as a reference drug. All the compounds were effective, amongst them 2d shows more prominent activity at 50 mg/k.g.p.o. The experimental results are statistically significant at P < 0.01 level.

  13. Lipid nanoparticles with a solid matrix (SLN, NLC, LDC) for oral drug delivery.

    Science.gov (United States)

    Muchow, Marc; Maincent, Philippe; Muller, Rainer H

    2008-12-01

    Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and lipid-drug conjugates (LDC), commonly produced by high-pressure homogenization, are interesting vectors for oral delivery of lipophilic and, to a certain extent, hydrophilic substances. Their production can be done without the use of organic solvents. Techniques to make them a physically stable delivery system have been developed. Scaling up of the production process from lab-size to large-scale dimensions using high-pressure homogenization can be easily achieved by using a different type of homogenizer. The machines used for large-scale production often yield an even better product quality than the lab-scale types. This review article covers the methods of production, characterization, mechanisms of oral bioavailability enhancement, scale-up, final oral dosage forms, and regulatory aspects of lipid nanoparticles for oral drug delivery. It focuses mainly on high-pressure homogenization production methods.

  14. Nanotechnology-based drug delivery systems for treatment of oral cancer: a review.

    Science.gov (United States)

    Calixto, Giovana; Bernegossi, Jéssica; Fonseca-Santos, Bruno; Chorilli, Marlus

    2014-01-01

    Oral cancer (oral cavity and oropharynx) is a common and aggressive cancer that invades local tissue, can cause metastasis, and has a high mortality rate. Conventional treatment strategies, such as surgery and chemoradiotherapy, have improved over the past few decades; however, they remain far from optimal. Currently, cancer research is focused on improving cancer diagnosis and treatment methods (oral cavity and oropharynx) nanotechnology, which involves the design, characterization, production, and application of nanoscale drug delivery systems. In medicine, nanotechnologies, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, gold nanoparticles, hydrogels, cyclodextrin complexes, and liquid crystals, are promising tools for diagnostic probes and therapeutic devices. The objective of this study is to present a systematic review of nanotechnology-based drug delivery systems for oral cancers.

  15. European Guidelines for Workplace Drug Testing in Oral Fluid.

    Science.gov (United States)

    Brcak, Michaela; Beck, Olof; Bosch, Tessa; Carmichael, Duncan; Fucci, Nadia; George, Claire; Piper, Mark; Salomone, Alberto; Schielen, Wim; Steinmeyer, Stefan; Taskinen, Sanna; Weinmann, Wolfgang

    2017-06-28

    These guidelines for Legally Defensible Workplace Drug Testing have been prepared and updated by the European Workplace Drug Testing Society (EWDTS). The European Guidelines are designed to establish best practice procedures whilst allowing individual countries to operate within the requirements of national customs and legislation. The EWDTS recommends that all European laboratories that undertake legally defensible workplace drug testing should use these guidelines as a template for accreditation. These guidelines are relevant to laboratory-based testing only. These guidelines follow current best practices and are constantly under review. This article is protected by copyright. All rights reserved.

  16. Targeting Receptors, Transporters and Site of Absorption to Improve Oral Drug Delivery

    Directory of Open Access Journals (Sweden)

    J.H. Hamman

    2007-01-01

    Full Text Available Although the oral route of drug administration is the most acceptable way of self-medication with a high degree of patient compliance, the intestinal absorption of many drugs is severely hampered by different biological barriers. These barriers comprise of biochemical and physical components. The biochemical barrier includes enzymatic degradation in the gastrointestinal lumen, brush border and in the cytoplasm of the epithelial cells as well as efflux transporters that pump drug molecules from inside the epithelial cell back to the gastrointestinal lumen. The physical barrier consists of the epithelial cell membranes, tight junctions and mucus layer. Different strategies have been applied to improve the absorption of drugs after oral administration, which range from chemical modification of drug molecules and formulation technologies to the targeting of receptors, transporters and specialized cells such as the gut-associated lymphoid tissues. This review focuses specifically on the targeting of receptor-mediated endocytosis, transporters and the absorption-site as methods of optimizing intestinal drug absorption. Intestinal epithelial cells express several nutrient transporters that can be targeted by modifying the drug molecule in such a way that it is recognized as a substrate. Receptor-mediated endocytosis is a transport mechanism that can be targeted for instance by linking a receptor substrate to the drug molecule of interest. Many formulation strategies exist for enhancing drug absorption of which one is to deliver drugs at a specific site in the gastrointestinal tract where optimum drug absorption takes place.

  17. Targeting receptors, transporters and site of absorption to improve oral drug delivery.

    Science.gov (United States)

    Hamman, J H; Demana, P H; Olivier, E I

    2007-01-01

    Although the oral route of drug administration is the most acceptable way of self-medication with a high degree of patient compliance, the intestinal absorption of many drugs is severely hampered by different biological barriers. These barriers comprise of biochemical and physical components. The biochemical barrier includes enzymatic degradation in the gastrointestinal lumen, brush border and in the cytoplasm of the epithelial cells as well as efflux transporters that pump drug molecules from inside the epithelial cell back to the gastrointestinal lumen. The physical barrier consists of the epithelial cell membranes, tight junctions and mucus layer. Different strategies have been applied to improve the absorption of drugs after oral administration, which range from chemical modification of drug molecules and formulation technologies to the targeting of receptors, transporters and specialized cells such as the gut-associated lymphoid tissues. This review focuses specifically on the targeting of receptor-mediated endocytosis, transporters and the absorption-site as methods of optimizing intestinal drug absorption. Intestinal epithelial cells express several nutrient transporters that can be targeted by modifying the drug molecule in such a way that it is recognized as a substrate. Receptor-mediated endocytosis is a transport mechanism that can be targeted for instance by linking a receptor substrate to the drug molecule of interest. Many formulation strategies exist for enhancing drug absorption of which one is to deliver drugs at a specific site in the gastrointestinal tract where optimum drug absorption takes place.

  18. Drug: D00380 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00380 Drug Tolbutamide (JP16/USP/INN); Orinase (TN) C12H18N2O3S 270.1038 270.3479 D00380.gif Antidiabetic...lycemic agents map07051 Antidiabetics map07055 Sulfonamide derivatives - overview... Agents affecting metabolism 39 Other agents affecting metabolism 396 Antidiabetic agents 3961 Sulfonylureas.../INN) USP drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic Agents Tolbutamide D00380 T

  19. Nanotechnology-based drug delivery systems for treatment of oral cancer: a review

    Directory of Open Access Journals (Sweden)

    Calixto G

    2014-08-01

    Full Text Available Giovana Calixto, Jéssica Bernegossi, Bruno Fonseca-Santos, Marlus Chorilli School of Pharmaceutical Sciences, Department of Drugs and Pharmaceuticals, São Paulo State University (UNESP, São Paulo, Brazil Abstract: Oral cancer (oral cavity and oropharynx is a common and aggressive cancer that invades local tissue, can cause metastasis, and has a high mortality rate. Conventional treatment strategies, such as surgery and chemoradiotherapy, have improved over the past few decades; however, they remain far from optimal. Currently, cancer research is focused on improving cancer diagnosis and treatment methods (oral cavity and oropharynx nanotechnology, which involves the design, characterization, production, and application of nanoscale drug delivery systems. In medicine, nanotechnologies, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, gold nanoparticles, hydrogels, cyclodextrin complexes, and liquid crystals, are promising tools for diagnostic probes and therapeutic devices. The objective of this study is to present a systematic review of nanotechnology-based drug delivery systems for oral cancers. Keywords: targeted delivery, oral squamous cell carcinoma, oral cancer treatment

  20. Patient adherence to oral anticancer drugs: an emerging issue in modern oncology.

    Science.gov (United States)

    Foulon, V; Schöffski, P; Wolter, P

    2011-01-01

    The steady increase in the use of oral anticancer drugs in modern oncology has created a paradigm shift, challenging traditional attitudes towards cancer care and requiring new concepts of organization of oncology services. Important issues are the prolonged treatment period, management of toxicity, treatment adherence, reimbursement conditions and patient and family education. Although most patients generally prefer oral therapy over intravenous treatment for reasons of convenience, the daily use of oral anticancer drugs can be a challenging commitment for many patients. Reports on adherence and persistence among patients with cancer show that adherence ranges from 16% to 100%, depending on the type of therapy and the measurement/definition of adherence. Apart from demographic, disease and therapy related factors, the determinants that mostly influence (non-)adherence are the satisfaction with care activities performed at the initiation of the drug treatment, and the perceived necessity of treatment. Therefore, patient education addressing these issues is considered the cornerstone of successful oral anticancer treatment. Studies examining the role of different health care providers in the pharmacotherapeutic care of patients with cancer, treated with oral anti-cancer drugs, support the need for a multidisciplinary approach to achieve a maximum benefit for the individual patient and consequently for the whole health system. Limiting adverse events and developing appropriate supportive care are only some aspects that need to be considered in this.

  1. Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals.

    Science.gov (United States)

    Rajabalaya, Rajan; Musa, Muhammad Nuh; Kifli, Nurolaini; David, Sheba R

    2017-01-01

    Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations.

  2. Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals

    Science.gov (United States)

    Rajabalaya, Rajan; Musa, Muhammad Nuh; Kifli, Nurolaini; David, Sheba R

    2017-01-01

    Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations. PMID:28243062

  3. Soft-Template-Synthesized Mesoporous Carbon for Oral Drug Delivery

    Energy Technology Data Exchange (ETDEWEB)

    Saha, Dipendu [ORNL; Warren, Kaitlyn E [ORNL; Naskar, Amit K [ORNL

    2014-01-01

    Template-synthesized mesoporous carbons were successfully used in in vitro investigations of controlled delivery of three model drugs, captopril, furosemide, and ranitidine hydrochloride. Captopril and furosemide exhibited desorption kinetics over 30 40 h, and ranitidine HCl had a complete release time of 5 10 h. As evident from the slow release kinetics, we contend that our mesoporous carbon is an improved drug-delivery medium compared to state-of-the-art porous silica-based substrates. The mesoporous carbons, synthesized from phloroglucinol and lignin, a synthetic and a sustainable precursor, respectively, exhibit BET surface area of 200 400 m2 g-1 and pore volume of 0.2 0.6 cm3 g-1. The phloroglucinol-based carbon has narrower pore widths and higher pore volume than the lignin-derived counterpart and maintains a longer release time. Numerical modeling of the release kinetics data reveals that the diffusivities of all the drugs from lignin-based carbon media are of equivalent magnitude (10-22 to 10-24 m2 s-1). However, a tailored reduction of pore width in the sorbent reduces the diffusivity of smaller drug molecules (captopril) by an order of magnitude. Thus, engineered pore morphology in our synthesized carbon sorbent, along with its potential to tailor the chemistry of its interaction with sorbet, can be exploited for optimal delivery system of a preferred drug within its therapeutic level and below the level of toxicity.

  4. Evaluation of the anti-diabetic properties ofMucuna pruriensseed extract

    Institute of Scientific and Technical Information of China (English)

    Stephen O Majekodunmi; Ademola A Oyagbemi; Solomon Umukoro; Oluwatoyin A Odeku

    2011-01-01

    Objective:To explore the antidiabetic properties ofMucuna pruriens(M. pruriens).Methods:Diabetes was induced in Wistar rats by single intravenous injection of120 mg/kg of alloxan monohydrate and different doses of the extract were administered to diabetic rats. The blood glucose level was determined using a glucometer and results were compared with normal and untreated diabetic rats. The acute toxicity was also determined in albino mice.Results:Results showed that the administration of5, 10, 20, 30, 40, 50, and100 mg/kg of the crude ethanolic extract ofM. pruriens seeds to alloxan-induced diabetic rats (plasma glucose> 450mg/dL) resulted in18.6%, 24.9%, 30.8%, 41.4%, 49.7%, 53.1% and 55.4% reduction, respectively in blood glucose level of the diabetic rats after 8h of treatment while the administration of glibenclamide (5mg/kg/day) resulted in59.7% reduction. Chronic administration of the extract resulted in a significant dose dependent reduction in the blood glucose level (P<0.001). It also showed that the antidiabetic activity ofM. pruriens seeds resides in the methanolic and ethanolic fractions of the extract. Acute toxicity studies indicated that the extract was relatively safe at low doses, although some adverse reactions were observed at higher doses (8-32 mg/kg body weight), no death was recorded. Furthermore, oral administration ofM. pruriens seed extract also significantly reduced the weight loss associated with diabetes.Conclusions: The study clearly supports the traditional use ofM. pruriens for the treatment of diabetes and indicates that the plant could be a good source of potent antidiabetic drug.

  5. In Vitro and In Vivo Antidiabetic Evaluation of Selected Culinary-Medicinal Mushrooms (Agaricomycetes).

    Science.gov (United States)

    Singh, Varinder; Bedi, Gurleen Kaur; Shri, Richa

    2017-01-01

    Management of type 2 diabetes by delaying or preventing glucose absorption using natural products is gaining significant attention. Edible mushrooms are well documented for their nutritional and medicinal properties. This investigation was designed to evaluate the antidiabetic activity of aqueous extracts of selected culinary-medicinal mushrooms, namely, Pleurotus ostreatus, Calocybe indica, and Volvariella volvacea, using in vitro models (α-amylase inhibition assay, glucose uptake by yeast cells, and glucose adsorption capacity). The most active extract was subsequently examined in vivo using the oral starch tolerance test in mice. All prepared extracts showed dose-dependent inhibition of α-amylase and an increase in glucose transport across yeast cells. C. indica extract was the most active α-amylase inhibitor (half-maximal inhibitory concentration, 18.07 ± 0.75 mg/mL) and exhibited maximum glucose uptake by yeast cells (77.53 ± 0.97% at 35 mg/mL). All extracts demonstrated weak glucose adsorption ability. The positive in vitro tests for C. indica paved the way for in vivo studies. C. indica extract (200 and 400 mg/kg) significantly (P < 0.05) reduced postprandial blood glucose peaks in mice challenged with starch. The extract (400 mg/kg) and acarbose normalized blood glucose levels at 180 minutes, when they were statistically similar to values in normal mice. Thus, it may be concluded that the antidiabetic effect of C. indica is mediated by inhibition of starch metabolism (α-amylase inhibition), increased glucose uptake by peripheral cells (promotion of glucose uptake by yeast cells), and mild entrapment (adsorption) of glucose. Hence, C. indica can be developed as antidiabetic drug after detailed pharmacological studies.

  6. Antidiabetic and Antioxidant Activities of Ethanolic Extract of Dried Flowers of Moringa oleifera in Streptozotocin-induced Diabetic Rats

    National Research Council Canada - National Science Library

    Rotimi Olusanya Arise; Oluwaseun Ruth Aburo; Samuel Tobi Farohunbi; Adenike Adebola Adewale

    2016-01-01

    This study was undertaken to determine the antidiabetic and antioxidant effects of oral administration of ethanolic extract of Moringa oleiferaflower on stretozotocin-induced diabetic rats at 100, 200, and 300 mg/kg b.w. Thirty (30...

  7. The mucoadhesive and gastroretentive properties of hydrophobin-coated porous silicon nanoparticle oral drug delivery systems.

    Science.gov (United States)

    Sarparanta, Mirkka P; Bimbo, Luis M; Mäkilä, Ermei M; Salonen, Jarno J; Laaksonen, Päivi H; Helariutta, A M Kerttuli; Linder, Markus B; Hirvonen, Jouni T; Laaksonen, Timo J; Santos, Hélder A; Airaksinen, Anu J

    2012-04-01

    Impediments to intestinal absorption, such as poor solubility and instability in the variable conditions of the gastrointestinal (GI) tract plague many of the current drugs restricting their oral bioavailability. Particulate drug delivery systems hold great promise in solving these problems, but their effectiveness might be limited by their often rapid transit through the GI tract. Here we describe a bioadhesive oral drug delivery system based on thermally-hydrocarbonized porous silicon (THCPSi) functionalized with a self-assembled amphiphilic protein coating consisting of a class II hydrophobin (HFBII) from Trichoderma reesei. The HFBII-THCPSi nanoparticles were found to be non-cytotoxic and mucoadhesive in AGS cells, prompting their use in a biodistribution study in rats after oral administration. The passage of HFBII-THCPSi nanoparticles in the rat GI tract was significantly slower than that of uncoated THCPSi, and the nanoparticles were retained in stomach by gastric mucoadhesion up to 3 h after administration. Upon entry to the small intestine, the mucoadhesive properties were lost, resulting in the rapid transit of the nanoparticles through the remainder of the GI tract. The gastroretentive drug delivery system with a dual function presented here is a viable alternative for improving drug bioavailability in the oral route.

  8. SELF EMULSIFYING DELIVERY SYSTEM -MOSTLY DISCUSSED BUT STILL REMAINED CHALLENGING ASPECT TO ENHANCE THE ORAL ABSORPTION OF LIPOPHILIC DRUG

    National Research Council Canada - National Science Library

    Niranjan Chivate; Kiran Wadkar; Rohit Shah; Anuradha Chivate

    2016-01-01

    ... in the gastro-intestinal lumen or other aqueous media. Therefore in order to be delivered orally and to achieve acceptable bioavailability, lipophilic drugs require a co-administered drug delivery system...

  9. Evaluation of commercial multi-drug oral fluid devices to identify 39 new amphetamine-designer drugs.

    Science.gov (United States)

    Nieddu, Maria; Burrai, Lucia; Trignano, Claudia; Boatto, Gianpiero

    2014-03-01

    Recently, the diffusion on the black market of new psychoactive substances not controlled and often sold as 'legal highs', is exponentially increasing in Europe. Generally, the first analysis for these drugs involves an immunoassay screening in urine or plasma. Actually, there is growing interest in the use of oral fluid (OF) as alternative specimen over conventional biological fluids for drug testing, because of the significant advantages, as a non-invasive collection under direct observation without undue embarrassment or invasion of privacy, and a good correlation with plasma analytical data. Few assays have been developed for detection of new psychoactive compounds in biological samples, so it is important to investigate how they may or may not react in pre-existing commercial immunoassays. In this paper, two different multi-drugs oral fluid screen devices (OFDs) (Screen® Multi-Drug OFD and GIMA One Step Multi-Line Screen Test OFD) were evaluated to determine the cross-reactivity of thirty-nine new amphetamine designer drugs, including twelve substances officially recognized as illicit by italian legislation. Cross-reactivity towards most drugs analyzed was <1 in assays targeting amphetamine (AMP) or methamphetamine (MET). Only two (p-methoxyamphetamine and p-methoxymethamphetamine) of all tested amphetamines gave a positive result.

  10. 75 FR 67031 - Oral Dosage Form New Animal Drugs; Domperidone

    Science.gov (United States)

    2010-11-01

    ... drug application (NADA) filed by Dechra, Ltd. The NADA provides for the veterinary prescription use of... Pits, Stoke-on-Trent, Staffordshire, ST7 1XW, United Kingdom, filed NADA 141-314 that provides for... periparturient mares. The NADA is approved as of September 9, 2010, and the regulations in 21 CFR part 520 are...

  11. Riluzole 5 mg/mL oral suspension: for optimized drug delivery in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Dyer AM

    2016-12-01

    Full Text Available Ann Margaret Dyer, Alan Smith PharmaSci Consulting Limited, Nottingham, UK Abstract: The aim of the present work is to extensively evaluate the pharmaceutical attributes of currently available riluzole presentations. The article describes the limitations and risks associated with the administration of crushed tablets, including the potential for inaccurate dosing and reduced rate of absorption when riluzole is administered with high-fat foods, and the advantages that a recently approved innovative oral liquid form of riluzole confers on amyotrophic lateral sclerosis (ALS patients. The article further evaluates the patented and innovative controlled flocculation technology used in the pseudoplastic suspension formulation to reduce the oral anesthesia seen with crushed tablets, resulting in optimized drug delivery for riluzole. Riluzole is the only drug licensed for treating ALS, which is the most common form of motor neurone disease and a highly devastating neurodegenerative condition. The licensed indication is to extend life or the time to mechanical ventilation. Until recently, riluzole was only available as an oral tablet dosage form in the UK; however, an innovative oral liquid form, Teglutik® 5 mg/mL oral suspension, is now available. An oral liquid formulation provides an important therapeutic option for patients with ALS, >80% of who may become unable to swallow solid oral dosage forms due to disease-related dysphagia. Prior to the launch of riluzole oral suspension, the only way for many patients to continue to take riluzole as their disease progressed was through crushed tablets. A novel suspension formulation enables more accurate dosing and consistent ongoing administration of riluzole. There are clear and important advantages such as enhanced patient compliance compared with crushed tablets administered with food or via an enteral feeding tube and the potential for an improved therapeutic outcome and enhanced quality of life for

  12. Polymeric particulate technologies for oral drug delivery and targeting: A pathophysiological perspective

    DEFF Research Database (Denmark)

    Hunter, A. Christy; Elsom, Jacqueline; Wibroe, Peter Popp;

    2012-01-01

    to optimize drug targeting and bioavailability. Frequently the carrier systems used are either constructed from or contain polymeric materials. Examples of these nanocarriers include polymeric nanoparticles, solid lipid nanocarriers, self-nanoemulsifying drug delivery systems and nanocrystals......Publication year: 2012 Source:Maturitas, Volume 73, Issue 1 A. Christy Hunter, Jacqueline Elsom, Peter P. Wibroe, S. Moein Moghimi The oral route for delivery of pharmaceuticals is the most widely used and accepted. Nanoparticles and microparticles are increasingly being applied within this arena...

  13. Review of pharmacological interactions of oral anticancer drugs provided at pharmacy department

    Directory of Open Access Journals (Sweden)

    E. Sánchez Gómez

    2014-07-01

    Full Text Available Abstract: Objective: To identify the pharmacologic interactions of oral anti-cancer drugs provided at an outpatient clinic. Material and methods: Anti-cancer drugs included in the Phamacotherapeutic Guideline of the Hospital were identified. A literature search was carried out on the pharmacologic interactions in MEDLINE® and EMBASE® (with the filer language English or Spanish, and the descriptors: “name of the anti-cancer drug” AND (“drug interactions” OR “pharmacokinetic”, Up-to-date®, MICROMEDEX® and the drug information sheet for the EMA and the FDA. Information was also gathered from the abstract presented to European and Spanish scientific meetings for the last 4 years. When an interaction was analyzed and had clinical relevance, the best pharmacotherapeutic interaction-free alternative was sought. Results: Twenty-three drugs were identified, of which Chlorambucil, Fludarabine, Lenalidomide, Melphalan, and Thalidomide were the active compounds with the lowest likelihood of producing a pharmacologic interaction. Tyrosine kinase inhibitors (particularly Erlotinib, Imatinib, Lapatinib, and Pazopanib are the drugs with highest number of pharmacologic interactions described, many of them with severe clinical consequences, with increases and decreases of the plasma levels of anti-cancer drugs. The active compounds identified that may have pharmacologic interactions with anticancer drugs were mainly: Allopurinol, Amiodarone, Carbamazepine, Dabigatran, Digoxin, Spironolactone, Phenytoin, Itraconazol, Repaglinide, Silodosin, Tamoxifen, Verapamil, and Warfarin. Pharmacologic interactions through the cytochrome P450 1A2, 2D6, 2C8, 2C9, 3A4 were the most important for tyrosine kinase inhibitors. Other non-pharmacologic compounds, with an important potential of producing relevant pharmacologic interaction were immunomodulators (Echinacea extracts and Hypericum perforatum. Conclusions: Oral anticancer drugs have numerous pharmacologic

  14. Effect of Adherence on Pharmacokinetic/Pharmacodynamic Relationships of Oral Targeted Anticancer Drugs.

    Science.gov (United States)

    Cardoso, Evelina; Csajka, Chantal; Schneider, Marie P; Widmer, Nicolas

    2017-06-20

    The emergence of oral targeted anticancer agents transformed several cancers into chronic conditions with a need for long-term oral treatment. Although cancer is a life-threatening condition, oncology medication adherence-the extent to which a patient follows the drug regimen that is intended by the prescriber-can be suboptimal in the long term, as in any other chronic disease. Poor adherence can impact negatively on clinical outcomes, notably because most of these drugs are given as a standard non-individualized dosage despite marked inter-individual variabilities that can lead to toxic or inefficacious drug concentrations. This has been especially studied with the prototypal drug imatinib. In the context of therapeutic drug monitoring (TDM), increasingly advocated for oral anticancer treatment optimization, unreported suboptimal adherence affecting drug intake history may lead to significant bias in the concentration interpretation and inappropriate dosage adjustments. In the same way, suboptimal adherence may also bias the results of pharmacokinetic modeling studies, which will affect in turn Bayesian TDM interpretation that relies on such population models. Detailed knowledge of the influence of adherence on plasma concentrations in pharmacokinetic studies or in routine TDM programs is however presently missing in the oncology field. Studies on this topic are therefore eagerly awaited to better pilot the treatment of cancer with the new targeted agents and to find their optimal dosage regimen. Hence, the development and assessment of effective medication adherence programs are warranted for these treatments.

  15. A facile nanoaggregation strategy for oral delivery of hydrophobic drugs by utilizing acid base neutralization reactions

    Science.gov (United States)

    Chen, Huabing; Wan, Jiangling; Wang, Yirui; Mou, Dongsheng; Liu, Hongbin; Xu, Huibi; Yang, Xiangliang

    2008-09-01

    Nanonization strategies have been used to enhance the oral availability of numerous drugs that are poorly soluble in water. Exploring a facile nanonization strategy with highly practical potential is an attractive focus. Here, we report a novel facile nanoaggregation strategy for constructing drug nanoparticles of poorly soluble drugs with pH-dependent solubility by utilizing acid-base neutralization in aqueous solution, thus facilitating the exploration of nanonization in oral delivery for general applicability. We demonstrate that hydrophobic itraconazole dissolved in acid solution formed a growing core and aggregated into nanoparticles in the presence of stabilizers. The nanoparticles, with an average diameter of 279.3 nm and polydispersity index of 0.116, showed a higher dissolution rate when compared with the marketed formulation; the average dissolution was about 91.3%. The in vivo pharmacokinetic studies revealed that the nanoparticles had a rapid absorption and enhanced oral availability. The diet state also showed insignificant impact on the absorption of itraconazole from nanoparticles. This nanoaggregation strategy is a promising nanonization method with a facile process and avoidance of toxic organic solvents for oral delivery of poorly soluble drugs with pH-dependent solubility and reveals a highly practical potential in the pharmaceutical and chemical industries.

  16. Silica-based systems for oral delivery of drugs, macromolecules and cells.

    Science.gov (United States)

    Diab, Roudayna; Canilho, Nadia; Pavel, Ileana A; Haffner, Fernanda B; Girardon, Maxime; Pasc, Andreea

    2017-04-20

    According to the US Food and Drug Administration and the European Food Safety Authority, amorphous forms of silica and silicates are generally recognized to be safe as oral delivery ingredients in amounts up to 1500mg per day. Silica is used in the formulation of solid dosage forms, e.g. tablets, as glidant or lubricant. The synthesis of silica-based materials depends on the payload nature, drug, macromolecule or cell, and on the target release (active or passive). In the literature, most of the examples deal with the encapsulation of drugs in mesoporous silica nanoparticles. Still to date limited reports concerning the delivery of encapsulated macromolecules and cells have been reported in the field of oral delivery, despite the multiple promising examples demonstrating the compatibility of the sol-gel route with biological entities, likewise the interest of silica as an oral carrier. Silica diatoms appear as an elegant, cost-effective and promising alternative to synthetic sol-gel-based materials. This review reports the latest advances silica-based systems and discusses the potential benefits and drawbacks of using silica for oral delivery of drugs, macromolecules or cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Hot embossing and mechanical punching of biodegradable microcontainers for oral drug delivery

    DEFF Research Database (Denmark)

    Petersen, Ritika Singh; Mahshid, Rasoul; Andersen, Nis Korsgaard

    2015-01-01

    A process has been developed to fabricate discrete three-dimensional microcontainers for oral drug delivery application in Poly-L-Lactic Acid (PLLA) polymer. The method combines hot embossing for the definition of holes in a PLLA film and mechanical punching to penetrate the polymer layer around ...

  18. Lack of nephrotoxicity of new oral platinum drug JM216 in lung cancer patients

    NARCIS (Netherlands)

    Fokkema, E; de Vries, EGE; Meijer, S; Groen, HJM

    Purpose: The purpose of this study was to assess renal function in patients treated with the oral platinum drug JM216 [bisacetato-ammine-dichloro-cyclohexylamine-platinum (IV)I, since the effects of JM216 on renal function have only partly been investigated using serum parameters or Cr-51-EDTA

  19. THE PRINCIPLES OF TASTE MASKING OF ORAL GELS WITH SYNTHETIC DRUGS

    Directory of Open Access Journals (Sweden)

    M. N. Anurova

    2015-01-01

    Full Text Available This article presents an experimental study of choice of flavorings and sweeteners for taste correction of oral gels. We have shown the possibility of changing of organoleptic properties for drugs with weak and strong unpleasant odor and taste. 

  20. Structural specificity of mucosal-cell transport and metabolism of peptide drugs: implication for oral peptide drug delivery

    Science.gov (United States)

    Bai, J. P.; Amidon, G. L.

    1992-01-01

    The brush border membrane of intestinal mucosal cells contains a peptide carrier system with rather broad substrate specificity and various endo- and exopeptidase activities. Small peptide (di-/tripeptide)-type drugs with or without an N-terminal alpha-amino group, including beta-lactam antibiotics and angiotensin-converting enzyme (ACE) inhibitors, are transported by the peptide transporter. Polypeptide drugs are hydrolyzed by brush border membrane proteolytic enzymes to di-/tripeptides and amino acids. Therefore, while the intestinal brush border membrane has a carrier system facilitating the absorption of di-/tripeptide drugs, it is a major barrier limiting oral availability of polypeptide drugs. In this paper, the specificity of peptide transport and metabolism in the intestinal brush border membrane is reviewed.

  1. Structural specificity of mucosal-cell transport and metabolism of peptide drugs: implication for oral peptide drug delivery

    Science.gov (United States)

    Bai, J. P.; Amidon, G. L.

    1992-01-01

    The brush border membrane of intestinal mucosal cells contains a peptide carrier system with rather broad substrate specificity and various endo- and exopeptidase activities. Small peptide (di-/tripeptide)-type drugs with or without an N-terminal alpha-amino group, including beta-lactam antibiotics and angiotensin-converting enzyme (ACE) inhibitors, are transported by the peptide transporter. Polypeptide drugs are hydrolyzed by brush border membrane proteolytic enzymes to di-/tripeptides and amino acids. Therefore, while the intestinal brush border membrane has a carrier system facilitating the absorption of di-/tripeptide drugs, it is a major barrier limiting oral availability of polypeptide drugs. In this paper, the specificity of peptide transport and metabolism in the intestinal brush border membrane is reviewed.

  2. Properties and formulation of oral drug delivery systems of protein and peptides

    Directory of Open Access Journals (Sweden)

    Semalty A

    2007-01-01

    Full Text Available Although most protein pharmaceuticals are usually formulated as a solution or suspension and delivered by invasive routes such as subcutaneous injections, major efforts in both academic and industrial laboratories have been directed towards developing effective oral formulations and increasing the oral absorption of intact protein through the use of formulations that protect the macromolecule and/or enhance it′s uptake into the intestinal mucosa. However, in spite of these major attempts, relatively little progress has been made. For the efficient delivery of peptides and proteins by non-parenteral route, in particular via the gastrointestinal tract, novel concepts are needed to overcome significant enzymatic and diffusion barriers. The properties of protein and peptides, which are of major interest in oral delivery, are highlighted in the article. This article reviews the various problems associated and novel approaches for formulation and development of oral protein and peptide drug delivery systems.

  3. Correlation of in vitro and in vivo models for the oral absorption of peptide drugs.

    Science.gov (United States)

    Föger, F; Kopf, A; Loretz, B; Albrecht, K; Bernkop-Schnürch, A

    2008-06-01

    The aim of this study was to evaluate two in vitro models, Caco-2 monolayer and rat intestinal mucosa, regarding their linear correlation with in vivo bioavailability data of therapeutic peptide drugs after oral administration in rat and human. Furthermore the impact of molecular mass (Mm) of the according peptides on their permeability was evaluated. Transport experiments with commercially available water soluble peptide drugs were conducted using Caco-2 cell monolayer grown on transwell filter membranes and with freshly excised rat intestinal mucosa mounted in Using type chambers. Apparent permeability coefficients (P (app)) were calculated and compared with in vivo data derived from the literature. It was shown that, besides a few exceptions, the Mm of peptides linearly correlates with permeability across rat intestinal mucosa (R (2) = 0.86; y = -196.22x + 1354.24), with rat oral bioavailability (R (2) = 0.64; y = -401.90x + 1268.86) as well as with human oral bioavailability (R (2) = 0.91; y = -359.43x + 1103.83). Furthermore it was shown that P (app) values of investigated hydrophilic peptides across Caco-2 monolayer displayed lower permeability than across rat intestinal mucosa. A correlation between P (app) values across rat intestinal mucosa and in vivo oral bioavailability in human (R (2) = 0.98; y = 2.11x + 0.34) attests the rat in vitro model to be a very useful prediction model for human oral bioavailability of hydrophilic peptide drugs. Presented correlations encourage the use of the rat in vitro model for the prediction of human oral bioavailabilities of hydrophilic peptide drugs.

  4. COST ANALYSIS OF LONG ESTABLISHED AND NEWER ORAL ANTIEPILEPTIC DRUGS AVAILABLE IN THE INDIAN MARKET

    Directory of Open Access Journals (Sweden)

    Phatak Abhishek M, Hotwani Jitendra H, Deshmukhkiran R, Panchal Sagar S, Naik Madhura S

    2015-10-01

    Full Text Available Background: Large number of pharmaceutical companies manufactures antiepileptic drugs in India. The price variations among the marketed drugs are wide. Aims: The present study was aimed to find the cost of different oral antiepileptic drugs available in Indian market as monotherapy, combination therapy and number of manufacturing companies for each, to evaluate difference in cost of different brands of same dosage of same active drug by calculating percentage variation of cost. Methods and Materials: Cost of a drug being manufactured by different companies, in the same strength and dosage forms was obtained from “Indian Drug Review” Vol. XXI, Issue No.4, 2014 and “Current Index of Medical Specialties” July-October 2014. The difference in the maximum and minimum price of the same drug manufactured by different pharmaceutical companies and percentage variation in price was calculated. Results: The percentage price variation noted of long-established drugs was – Phenytoin (50mg: 140%, Carbamazepine (100mg: 1033%, Phenobarbital (30mg : 730%, Valproic acid (300mg : 420%. Newer drugs –Levetiracetam (250mg: 75%, Lamotrigine (25mg: 66%, Topiramate (50mg: 108%, Zonisamide (100mg: 19%. Combination drugs – Phenobarbital + Phenytoin (30+100 mg: 354.55%. Conclusion: The percentage price variation of different brands of the same commonly used long-established oral antiepileptic drug manufactured in India is very wide. The formulation or brand of Antiepileptic drugs (AED’s should preferably not be changed since variations in bioavailability or different pharmacokinetic profiles may increase the potential for reduced effect or excessive side effects. Hence, manufacturing companies should aim to decrease the price variation while maintaining the therapeutic efficacy.

  5. Evaluation of Antidiabetic and Antihyperlipidemic Effects of Hydroalcoholic Extract of Leaves of Ocimum tenuiflorum (Lamiaceae and Prediction of Biological Activity of its Phytoconstituents

    Directory of Open Access Journals (Sweden)

    Subramani Parasuraman

    2015-01-01

    Full Text Available Objective: The aim was to evaluate the anti-diabetic and anti-hyperlipidemic effects of hydroalcoholic extract of leaves of Ocimum tenuiflorum (Lamiaceae and prediction of biological activities of its phytoconstituents using in vivo anti-diabetic model and in silico analysis respectively. Materials and Methods: The leaves of O. tenuiflorum were extracted with 60% ethanol, and the extract was used for further pharmacological screening. The acute toxicity of the extract was evaluated as per the guidelines set by the Organization for Economic Co-operation and Development, revised draft guidelines 423. The oral anti-diabetic activity of the hydroalcoholic extract of O. tenuiflorum (125, 250 and 500 mg/kg was studied against streptozotocin (STZ (50 mg/kg; i.p. + nicotinamide (120 mg/kg; i.p. induced diabetes mellitus. The animals were treated with the investigational plant extract and standard drug (glibenclamide for 21 consecutive days and the effect of hydroalcoholic extract of O. tenuiflorum on blood glucose levels was measured at regular intervals. At the end of the study, blood samples were collected from all the animals for biochemical estimation, then the animals were sacrificed and the liver and kidney were collected for organ weight analysis. Prediction for pharmacological and toxicological properties of phytoconstituents of O. tenuiflorum was carried out using online web tools such as online pass prediction and lazar toxicity prediction. Results: The hydroalcoholic extract of O. tenuiflorum showed significant anti-diabetic and anti-hyperlipidemic activity at 250 and 500 mg/kg, and this effect was comparable with that of glibenclamide. Predicted biological activities of phytoconstituents of O. tenuiflorum showed presence of various pharmacological actions, which includes anti-diabetic and anti-hyperlipidemic activities. Prediction of toxicological properties of phytoconstituents of O. tenuiflorum did not show any major toxic effects

  6. Advanced progress of microencapsulation technologies: in vivo and in vitro models for studying oral and transdermal drug deliveries.

    Science.gov (United States)

    Lam, P L; Gambari, R

    2014-03-28

    This review provides an overall discussion of microencapsulation systems for both oral and transdermal drug deliveries. Clinically, many drugs, especially proteins and peptides, are susceptible to the gastrointestinal tract and the first-pass metabolism after oral administration while some drugs exhibit low skin permeability through transdermal delivery route. Medicated microcapsules as oral and transdermal drug delivery vehicles are believed to offer an extended drug effect at a relatively low dose and provide a better patient compliance. The polymeric microcapsules can be produced by different microencapsulation methods and the drug microencapsulation technology provides the quality preservation for drug stabilization. The release of the entrapped drug is controlled and prolonged for specific usages. Some recent studies have focused on the evaluation of drug containing microcapsules on potential biological and therapeutic applications. For the oral delivery, in vivo animal models were used for evaluating possible treatment effects of drug containing microcapsules. For the transdermal drug delivery, skin delivery models were introduced to investigate the potential skin delivery of medicated microcapsules. Finally, the challenges and limitations of drug microencapsulation in real life are discussed and the commercially available drug formulations using microencapsulation technology for oral and transdermal applications are shown.

  7. Multilayer encapsulated mesoporous silica nanospheres as an oral sustained drug delivery system for the poorly water-soluble drug felodipine

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Liang [Department of Pharmaceutics, Shenyang Pharmaceutical University, P.O. Box 32, Liaoning Province, Shenyang 110016 (China); Sun, Hongrui [English Teaching Department, School of Basic Courses, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016 (China); Zhao, Qinfu; Han, Ning; Bai, Ling; Wang, Ying; Jiang, Tongying [Department of Pharmaceutics, Shenyang Pharmaceutical University, P.O. Box 32, Liaoning Province, Shenyang 110016 (China); Wang, Siling, E-mail: silingwang@syphu.edu.cn [Department of Pharmaceutics, Shenyang Pharmaceutical University, P.O. Box 32, Liaoning Province, Shenyang 110016 (China)

    2015-02-01

    We used a combination of mesoporous silica nanospheres (MSN) and layer-by-layer (LBL) self-assembly technology to establish a new oral sustained drug delivery system for the poorly water-soluble drug felodipine. Firstly, the model drug was loaded into MSN, and then the loaded MSN were repeatedly encapsulated by chitosan (CHI) and acacia (ACA) via LBL self-assembly method. The structural features of the samples were studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption. The encapsulating process was monitored by zeta-potential and surface tension measurements. The physical state of the drug in the samples was characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). The influence of the multilayer with different number of layers on the drug release rate was studied using thermal gravimetric analysis (TGA) and surface tension measurement. The swelling effect and the structure changes of the multilayer were investigated to explore the relationship between the drug release behavior and the state of the multilayer under different pH conditions. The stability and mucosa adhesive ability of the prepared nanoparticles were also explored. After multilayer coating, the drug release rate was effectively controlled. The differences in drug release behavior under different pH conditions could be attributed to the different states of the multilayer. And the nanoparticles possessed good stability and strong mucosa adhesive ability. We believe that this combination offers a simple strategy for regulating the release rate of poorly water-soluble drugs and extends the pharmaceutical applications of inorganic materials and polymers. - Highlights: • A combination of inorganic and organic materials was applied. • Mesoporous silica nanospheres (MSN) were used as drug carriers. • Chitosan and acacia were encapsulated through layer-by-layer self-assembly. • The release rate of the poorly

  8. Indirect competitive assays on DVD for direct multiplex detection of drugs of abuse in oral fluids.

    Science.gov (United States)

    Zhang, Lingling; Li, Xiaochun; Li, Yunchao; Shi, Xiaoli; Yu, Hua-Zhong

    2015-02-03

    On-site oral fluid testing for drugs of abuse has become prominent in order to take immediate administrative action in an enforcement process. Herein, we report a DVD technology-based indirect competitive immunoassay platform for the quantitative detection of drugs of abuse. A microfluidic approach was adapted to prepare multiplex immunoassays on a standard DVD-R, an unmodified multimode DVD/Blu-Ray drive to read signal, and a free disc-quality analysis software program to process the data. The DVD assay platform was successfully demonstrated for the simultaneous, quantitative detection of drug candidates (morphine and cocaine) in oral fluids with high selectivity. The detection limit achieved was as low as 1.0 ppb for morphine and 5.0 ppb for cocaine, comparable with that of standard mass spectrometry and ELISA methods.

  9. GLC determination of plasma drug levels after oral administration of clorazepate potassium salts.

    Science.gov (United States)

    Hoffman, D J; Chun, A H

    1975-10-01

    Plasma nordiazepam levels resulting from the oral administration of clorazepate potassium salts were determined by a sensitive GLC assay. Nordiazepam and the internal standard (diazepam) were selectively extracted into ether at pH 9.2, hydrolyzed to their respective benzophenones, and quantified by electron-capture detection. The assay was used in a comparative bioavailability study of single equimolar oral doses of monopotassium and dipotassium salts of clorazepate in dogs. Both clorazepate salts were rapidly absorbed and exhibited mean peak total drug levels after 1 hr. Clorazepate levels accounted for about 50% of the total drug levels present. No statistical difference in the plasma drug levels of clorazepate mono- and dipotassium salts and the metabolite was found in dogs.

  10. Drug: D09566 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available -peptidase 4 (DPP4) inhibitor [HSA:1803] [KO:K01278] hsa04974(1803) Protein digestion and absorption map07051 Antidiabetic...cting metabolism 39 Other agents affecting metabolism 396 Antidiabetic agents 3969 Others D09566 Linagliptin...P drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic Agents Linagliptin D09566 Linaglipt

  11. Drug: D06553 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ipeptidyl-peptidase 4 (DPP4) inhibitor [HSA:1803] [KO:K01278] hsa04974(1803) Protein digestion and absorption map07051 Antidiabetic...ents affecting metabolism 39 Other agents affecting metabolism 396 Antidiabetic agents 3969 Others D06553 Al...te (JAN/USAN) USP drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic Agents Alogliptin D

  12. Modified-chitosan nanoparticles: Novel drug delivery systems improve oral bioavailability of doxorubicin.

    Science.gov (United States)

    Khdair, Ayman; Hamad, Islam; Alkhatib, Hatim; Bustanji, Yasser; Mohammad, Mohammad; Tayem, Rabab; Aiedeh, Khaled

    2016-10-10

    The efficacy of most anticancer drugs is highly limited in vivo due mainly to poor pharmacokinetics behavior including poor bioavailability after extravascular administration. We have developed novel chitosan-modified polymeric nanoparticles for oral as well as i.v. administration. Nanoparticles were developed utilizing the double emulsion solvent evaporation technique for sustained delivery of various anticancer drugs. Chitosan diacetate (CDA) and chitosan triacetate (CTA) polymers were previously modified in our laboratory and used as novel matrix. Nanoparticles, loaded with various anticancer drugs, were characterized for particle size using dynamic light scattering as well as transmission electron microscopy and net surface charge using dynamic light scattering. Particles size was below 100nm in diameter and zeta potential ranged - (25-30). Encapsulation efficiency of anticancer drugs varied considerably and was dependent on the physicochemical characteristics of the encapsulated drug. However, chitosan triacetate nanoparticles showed relatively higher encapsulation efficiency than chitosan diacetate nanoparticles. In vitro release of encapsulated drugs was sustained over a period of 14days. Nanoparticles enhanced cellular accumulation of encapsulated drugs, compared to the free drugs, in vitro in MCF-7 and Caco-II tumor cell lines. In conclusion, diacetate and triacetate chitosan are novel polymers that can be used to formulate nanoparticles which efficiently encapsulated anticancer drugs, and sustained the release and enhanced tumor cellular uptake of these drugs. Further, chitosan triacetate nanoparticles enhanced oral bioavailability of doxorubicin. CDA and CTA nanoparticles can be used to efficiently deliver anticancer drugs and improve their in vivo profile. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Driving under the influence of drugs -- evaluation of analytical data of drugs in oral fluid, serum and urine, and correlation with impairment symptoms.

    Science.gov (United States)

    Toennes, Stefan W; Kauert, Gerold F; Steinmeyer, Stefan; Moeller, Manfred R

    2005-09-10

    A study was performed to acquire urine, serum and oral fluid samples in cases of suspected driving under the influence of drugs of abuse. Oral fluid was collected using a novel sampling/testing device (Dräger DrugTest System). The aim of the study was to evaluate oral fluid and urine as a predictor of blood samples positive for drugs and impairment symptoms. Analysis for cannabinoids, amphetamine and its derivatives, opiates and cocaine was performed in urine using the Mahsan Kombi/DOA4-test, in serum using immunoassay and gas chromatography-mass spectrometry (GC-MS) confirmation and in oral fluid by GC-MS. Police and medical officer observations of impairment symptoms were rated and evaluated using a threshold value for the classification of driving inability. Accuracy in correlating drug detection in oral fluid and serum were >90% for all substances and also >90% in urine and serum except for THC (71.0%). Of the cases with oral fluid positive for any drug 97.1% of corresponding serum samples were also positive for at least one drug; of drug-positive urine samples this were only 82.4%. In 119 of 146 cases, impairment symptoms above threshold were observed (81.5%). Of the cases with drugs detected in serum, 19.1% appeared not impaired which were the same with drug-positive oral fluid while more persons with drug-positive urine samples appeared uninfluenced (32.7%). The data demonstrate that oral fluid is superior to urine in correlating with serum analytical data and impairment symptoms of drivers under the influence of drugs of abuse.

  14. 3D Printing of Medicines: Engineering Novel Oral Devices with Unique Design and Drug Release Characteristics.

    Science.gov (United States)

    Goyanes, Alvaro; Wang, Jie; Buanz, Asma; Martínez-Pacheco, Ramón; Telford, Richard; Gaisford, Simon; Basit, Abdul W

    2015-11-02

    Three dimensional printing (3D printing) was used to fabricate novel oral drug delivery devices with specialized design configurations. Each device was loaded with multiple actives, with the intent of applying this process to the production of personalized medicines tailored at the point of dispensing or use. A filament extruder was used to obtain drug-loaded--paracetamol (acetaminophen) or caffeine--filaments of poly(vinyl alcohol) with characteristics suitable for use in fused-deposition modeling 3D printing. A multinozzle 3D printer enabled fabrication of capsule-shaped solid devices containing the drug with different internal structures. The design configurations included a multilayer device, with each layer containing drug, whose identity was different to the drug in the adjacent layers, and a two-compartment device comprising a caplet embedded within a larger caplet (DuoCaplet), with each compartment containing a different drug. Raman spectroscopy was used to collect 2-dimensional hyper spectral arrays across the entire surface of the devices. Processing of the arrays using direct classical least-squares component matching to produce false color representations of distribution of the drugs was used. This clearly showed a definitive separation between the drug layers of paracetamol and caffeine. Drug release tests in biorelevant bicarbonate media showed unique drug release profiles dependent on the macrostructure of the devices. In the case of the multilayer devices, release of both paracetamol and caffeine was simultaneous and independent of drug solubility. With the DuoCaplet design, it was possible to engineer either rapid drug release or delayed release by selecting the site of incorporation of the drug in the device; the lag-time for release from the internal compartment was dependent on the characteristics of the external layer. The study confirms the potential of 3D printing to fabricate multiple-drug containing devices with specialized design

  15. Orally dissolving strips: A new approach to oral drug delivery system.

    Science.gov (United States)

    Bala, Rajni; Pawar, Pravin; Khanna, Sushil; Arora, Sandeep

    2013-04-01

    Recently, fast dissolving films are gaining interest as an alternative of fast dissolving tablets. The films are designed to dissolve upon contact with a wet surface, such as the tongue, within a few seconds, meaning the consumer can take the product without need for additional liquid. This convenience provides both a marketing advantage and increased patient compliance. As the drug is directly absorbed into systemic circulation, degradation in gastrointestinal tract and first pass effect can be avoided. These points make this formulation most popular and acceptable among pediatric and geriatric patients and patients with fear of choking. Over-the-counter films for pain management and motion sickness are commercialized in the US markets. Many companies are utilizing transdermal drug delivery technology to develop thin film formats. In the present review, recent advancements regarding fast dissolving buccal film formulation and their evaluation parameters are compiled.

  16. Increasing the oral bioavailability of the poorly water soluble drug itraconazole with ordered mesoporous silica.

    Science.gov (United States)

    Mellaerts, Randy; Mols, Raf; Jammaer, Jasper A G; Aerts, Caroline A; Annaert, Pieter; Van Humbeeck, Jan; Van den Mooter, Guy; Augustijns, Patrick; Martens, Johan A

    2008-05-01

    This study aims to evaluate the in vivo performance of ordered mesoporous silica (OMS) as a carrier for poorly water soluble drugs. Itraconazole was selected as model compound. Physicochemical characterization was carried out by SEM, TEM, nitrogen adsorption, DSC, TGA and in vitro dissolution. After loading itraconazole into OMS, its oral bioavailability was compared with the crystalline drug and the marketed product Sporanox in rabbits and dogs. Plasma concentrations of itraconazole and OH-itraconazole were determined by HPLC-UV. After administration of crystalline itraconazole in dogs (20mg), no systemic itraconazole could be detected. Using OMS as a carrier, the AUC0-8 was boosted to 681+/-566 nM h. In rabbits, the AUC0-24 increased significantly from 521+/-159 nM h after oral administration of crystalline itraconazole (8 mg) to 1069+/-278 nM h when this dose was loaded into OMS. Tmax decreased from 9.8+/-1.8 to 4.2+/-1.8h. No significant differences (AUC, Cmax, and Tmax) could be determined when comparing OMS with Sporanox in both species. The oral bioavailability of itraconazole formulated with OMS as a carrier compares well with the marketed product Sporanox, in rabbits as well as in dogs. OMS can therefore be considered as a promising carrier to achieve enhanced oral bioavailability for drugs with extremely low water solubility.

  17. Pharmacological investigations of the anti-diabetic effect of Cortex Moutan and its active component paeonol.

    Science.gov (United States)

    Lau, C H; Chan, C M; Chan, Y W; Lau, K M; Lau, T W; Lam, F C; Law, W T; Che, C T; Leung, P C; Fung, K P; Ho, Y Y; Lau, C B S

    2007-11-01

    Cortex Moutan (CM, root bark of Paeonia suffruticosa Andr.) is one of the common herbs found in anti-diabetic traditional Chinese medicine formulae. To study the potential anti-diabetic mechanisms of CM, four in vitro models (intestinal brush border membrane vesicles (BBMV), rat hepatoma cell line H4IIE, human skin fibroblasts cell line Hs68 and mouse adipocytes 3T3-L1) were used. CM showed significant in vitro anti-diabetic effects by inhibiting glucose uptake of BBMV and enhancing glucose uptake into Hs68 and 3T3-L1 cells. Using bioassay-guided fractionation, paeonol was confirmed to be one of the active constituents for inhibiting BBMV glucose uptake. With neonatal-streptozotocin diabetic rats, paeonol (200 and 400mg/kgbody wt.) was found to improve oral glucose tolerance in vivo. To the best of our knowledge, this is the first report on the anti-diabetic effect of paeonol.

  18. Drug: D00336 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Micronase (TN) C23H28ClN3O5S 493.1438 494.0035 D00336.gif Antidiabetic [DS:H00409] Same as: C07022 Therapeut...onamide derivatives - hypoglycemic agents map07051 Antidiabetics map07232 Potassium channel blocking and ope... metabolism 39 Other agents affecting metabolism 396 Antidiabetic agents 3961 Sulfonylureas D00336 Glibencla...NN); Glyburide (USP) USP drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic Agents Glybu

  19. Drug: D00945 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 0961 392.8996 D00945.gif Antidiabetic [DS:H00409] Therapeutic category: 3969 ATC code: A10BG03 peroxisome pr...way CYP induction: CYP3A [HSA:1576 1577 1551] map07051 Antidiabetics map07222 Per...3 Agents affecting metabolism 39 Other agents affecting metabolism 396 Antidiabetic agents 3969 Others D0094...(JP16/USP) USP drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic

  20. A comparative study of oral and intravenous drug-dependent patients on three dimensions of personality.

    Science.gov (United States)

    Gossop, M R

    1978-01-01

    In an investigation of personality differences between oral and intravenous drug addicts, 59 subjects attending a London clinic were given the Eysenck Personality Questionnaire. Both groups scored highly on the neuroticism and psychoticism dimensions, though oral users were found to have significantly higher scores on both of these scales. High P scorers have been found to be cold, unfriendly, hostile, etc., and it is suggested that the lower P scores of the intravenous users may be partly due to possible hostility-reducing effects of the narcotics used by this group. Other implications of these findings are also discussed.

  1. Loading of Drug-Polymer Matrices in Microreservoirs for Oral Drug Delivery

    DEFF Research Database (Denmark)

    Petersen, Ritika Singh; Keller, Stephan Sylvest; Boisen, Anja

    2016-01-01

    For major advances in microfabricated drug delivery systems (DDS), fabrication methods with high throughput using biocompatible polymers are required. Once these DDS are fabricated, loading of drug poses a significant challenge. Here, hot punching is presented as an innovative method for drug...... loading in microfabricated DDS. The microfabricated DDS are microcontainers fabricated in photoresist SU-8 and biopolymer poly-L-lactic-acid (PLLA). Furosemide (F) drug is embedded in poly-ε-caprolactone (PCL) polymer matrix. This F-PCL drug polymer matrix is loaded in SU-8 and PLLA microcontainers using...... hot punching with >99% yield. Thus, it is illustrated that hot punching allows high-throughput, parallel loading of 3D polymer microcontainers with drug-polymer matrices in a single process step....

  2. A ceramic drug delivery vehicle for oral administration of highly potent opioids.

    Science.gov (United States)

    Forsgren, Johan; Jämstorp, Erik; Bredenberg, Susanne; Engqvist, Håkan; Strømme, Maria

    2010-01-01

    Pellets composed of the ceramic material Halloysite and microcrystalline cellulose were synthesized with the aim of producing a drug delivery vehicle for sustained release of the opioid Fentanyl with low risk for dose dumping at oral intake of the highly potent drug. Drug release profiles of intact and crushed pellets, to simulate swallowing without or with chewing, in pH 6.8, pH 1, and in 48% ethanol were recorded in order to replicate the conditions in the small intestines, in the stomach, as well as cointake of the drug with alcohol. The drug release was analyzed by employing the Weibull equation, which showed that the release profiles were either governed by fickian diffusion (intact pellets in pH 6.8 and in ethanol) or by diffusion in a fractal or disordered pore network (intact pellets in pH 1 and crushed pellets in all solutions). A sustained release for approximately 3-4 h was obtained in all studied solutions from intact pellets, whereas crushed pellets released the drug content during approximately 2-3 h. The finding that a sustained release profile could be obtained both in alcohol and after crushing of the pellets, shows that the ceramic carrier under investigation, at least to some extent, hampers dose dumping, and may thus be a promising material in future developments of new opioid containing oral dosage forms.

  3. Evaluation of human pharmacokinetics, therapeutic dose and exposure predictions using marketed oral drugs.

    Science.gov (United States)

    McGinnity, D F; Collington, J; Austin, R P; Riley, R J

    2007-06-01

    In this article approaches to predict human pharmacokinetics (PK) are discussed and the capability of the exemplified methodologies to estimate individual PK parameters and therapeutic dose for a set of marketed oral drugs has been assessed. For a set of 63 drugs where the minimum efficacious concentration (MEC) and human PK were known, the clinical dose was shown to be well predicted or in some cases over-estimated using a simple one-compartment oral PK model. For a subset of these drugs, in vitro potency against the primary human targets was gathered, and compared to the observed MEC. When corrected for plasma protein binding, the MEC of the majority of compounds was GFR. For approximately 90% of compounds studied, the predicted CL using in vitro-in vivo (IVIV) extrapolation together with a CL(renal) estimate, where appropriate, was within 2-fold of that observed clinically. Encouragingly volume of distribution at steady state (V(ss)) estimated in preclinical species (rat and dog) when corrected for plasma protein binding, predicted human V(ss) successfully on the majority of occasions--73% of compounds within 2-fold. In this laboratory, absorption estimated from oral rat PK studies was lower than the observed human absorption for most drugs, even when solubility and permeability appeared not to be limiting. Preliminary data indicate absorption in the dog may be more representative of human for compounds absorbed via the transcellular pathway. Using predicted PK and MEC values estimated from in vitro potency assays there was a good correlation between predicted and observed dose. This analysis suggests that for oral therapies, human PK parameters and clinical dose can be estimated from a consideration of data obtained from in vitro screens using human derived material and in vivo animal studies. The benefits and limitations of this holistic approach to PK and dose prediction within the drug discovery process are exemplified and discussed.

  4. Enhancement of oral bioavailability of cyclosporine A: comparison of various nanoscale drug-delivery systems.

    Science.gov (United States)

    Wang, Kai; Qi, Jianping; Weng, Tengfei; Tian, Zhiqiang; Lu, Yi; Hu, Kaili; Yin, Zongning; Wu, Wei

    2014-01-01

    A variety of nanoscale delivery systems have been shown to enhance the oral absorption of poorly water-soluble and poorly permeable drugs. However, the performance of these systems has seldom been evaluated simultaneously. The aim of this study was to compare the bioavailability enhancement effect of lipid-based nanocarriers with poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to highlight the importance of the lipid composition, with cyclosporine A (CyA) as a model drug. CyA-loaded PLGA NPs, nanostructured lipid carriers (NLCs), and self-microemulsifying drug-delivery systems (SMEDDS) were prepared. The particle size of PLGA NPs (182.2 ± 12.8 nm) was larger than that of NLCs (89.7 ± 9.0 nm) and SMEDDS (26.9 ± 1.9 nm). All vehicles are charged negatively. The entrapment efficiency of PLGA NPs and NLCs was 87.6%± 1.6% and 80.3%± 0.6%, respectively. In vitro release tests indicated that the cumulative release of CyA was lower than 4% from all vehicles, including Sandimmun Neoral(®), according to the dialysis method. Both NLCs and SMEDDS showed high relative oral bioavailability, 111.8% and 73.6%, respectively, after oral gavage administration to beagle dogs, which was not statistically different from commercial Sandimmun Neoral(®). However, PLGA NPs failed to achieve efficient absorption, with relative bioavailability of about 22.7%. It is concluded that lipid-based nanoscale drug-delivery systems are superior to polymeric NPs in enhancing oral bioavailability of poorly water-soluble and poorly permeable drugs.

  5. Multilayer encapsulated mesoporous silica nanospheres as an oral sustained drug delivery system for the poorly water-soluble drug felodipine.

    Science.gov (United States)

    Hu, Liang; Sun, Hongrui; Zhao, Qinfu; Han, Ning; Bai, Ling; Wang, Ying; Jiang, Tongying; Wang, Siling

    2015-02-01

    We used a combination of mesoporous silica nanospheres (MSN) and layer-by-layer (LBL) self-assembly technology to establish a new oral sustained drug delivery system for the poorly water-soluble drug felodipine. Firstly, the model drug was loaded into MSN, and then the loaded MSN were repeatedly encapsulated by chitosan (CHI) and acacia (ACA) via LBL self-assembly method. The structural features of the samples were studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption. The encapsulating process was monitored by zeta-potential and surface tension measurements. The physical state of the drug in the samples was characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). The influence of the multilayer with different number of layers on the drug release rate was studied using thermal gravimetric analysis (TGA) and surface tension measurement. The swelling effect and the structure changes of the multilayer were investigated to explore the relationship between the drug release behavior and the state of the multilayer under different pH conditions. The stability and mucosa adhesive ability of the prepared nanoparticles were also explored. After multilayer coating, the drug release rate was effectively controlled. The differences in drug release behavior under different pH conditions could be attributed to the different states of the multilayer. And the nanoparticles possessed good stability and strong mucosa adhesive ability. We believe that this combination offers a simple strategy for regulating the release rate of poorly water-soluble drugs and extends the pharmaceutical applications of inorganic materials and polymers.

  6. The role of co-morbidity in the selection of antidiabetic pharmacotherapy in type-2 diabetes.

    Science.gov (United States)

    Tschöpe, Diethelm; Hanefeld, Markolf; Meier, Juris J; Gitt, Anselm K; Halle, Martin; Bramlage, Peter; Schumm-Draeger, Petra-Maria

    2013-04-10

    Metformin is, if not contraindicated and if tolerated, usually preferred over other antidiabetic drugs for the first line treatment of type-2 diabetes. The particular decision on which antidiabetic agent to use is based on variables such as efficacy, cost, potential side effects, effects on weight, comorbidities, hypoglycemia, risk, and patient preferences. However, there is no guidance how to consider these in the selection of antidiabetic drug treatment. In this work, we aimed to summarize available evidence and tried to give pragmatic treatment recommendations from a clinical practice perspective.There are clear contraindications for some drugs in those with impaired renal and liver function and precautions in those with heart failure for the use of metformin (NYHA III-IV) and glitazones. On the other hand, GLP-1 analogs, DPP-4 inhibitors and acarbose are generally less critical and can be used in the majority of patients. We identified the following gaps with respect to the selection of antidiabetic drug treatment in patients with co-morbid disease conditions: 1) Guidelines fail to give advice on the use of specific antidiabetic drugs in patients with co-morbidity. 2) The literature is deficient in studies documenting antidiabetic drug use in patients with severely impaired renal function, diabetic retinopathy, cerebrovascular disease and systolic heart failure. 3) Further there are no specific data on patients with multiple of these co-morbid disease conditions. We postulate that differential use of antidiabetic drugs in patients with co-morbid disease constellations will help to reduce treatment related complications and might improve prognosis.

  7. Impact of gastrointestinal lipolysis on oral lipid-based formulations and bioavailability of lipophilic drugs.

    Science.gov (United States)

    Carrière, Frédéric

    2016-06-01

    Oil-in-water emulsions are common vehicles for lipids as nutrients and for the delivery of poorly water-soluble drugs. Enhancing oral bioavailability of these drugs using lipid-based formulations (LBF) or self-emulsifying drug delivery systems is one of the current challenges in pharmaceutical industry. Many of the compounds found in LBF (acylglycerols, surfactants with esterified fatty acids, …) are however potential substrates for digestive enzymes. Their digestion (or lipolysis) in the gastrointestinal (GI) tract is critical for drug dissolution and absorption: it can be beneficial (drug solubilization/dispersion) or deleterous (drug precipitation) depending on the drug-LBF association. A better understanding of the fate of LBF in the GI tract is therefore required to engineer efficient lipid-based drug delivery systems. In vitro models for testing simultaneously LBF digestion and drug dispersion are in development to predict drug solubilization and bioavailability, select the best drug-LBF association and obtain better in vitro-in vivo correlations. So far, research in this area has focused on LBF lipolysis under intestinal conditions because the small intestine is the main target for drug delivery and absorption, as well as the main site of digestion by pancreatic enzymes. Lipolysis however starts within the stomach through the action of gastric lipase, the first enzyme involved in fat digestion in humans. In vitro digestion experiments show that most LBFs are submitted to gastric lipolysis, and therefore, both intragastric and intestinal digestions are critical for the fate of LBF and drug solubility.

  8. Supercritical impregnation of polymer matrices spatially confined in microcontainers for oral drug delivery: Effect of temperature, pressure and time

    DEFF Research Database (Denmark)

    Marizza, Paolo; Pontoni, L.; Rindzevicius, Tomas

    2016-01-01

    parameters(temperature, pressure, time, drug concentration in the supercritical phase) was elucidated with respectto the loading capacity. The microcontainer filling was observed by means of optical macroimaging, X-ray microtomography and scanning electron microscopy. The physical state of the drug...... described. The drug loading can be controlled with high accuracy and reproducibility andthe impregnated drug is in amorphous state. These results demonstrate that SCI can be used as a highthroughput loading technique for microfabricated devices for oral drug delivery....

  9. Pharmacokinetic, pharmacodynamic and biodistribution following oral administration of nanocarriers containing peptide and protein drugs.

    Science.gov (United States)

    Griffin, Brendan T; Guo, Jianfeng; Presas, Elena; Donovan, Maria D; Alonso, María J; O'Driscoll, Caitriona M

    2016-11-15

    The influence of nanoparticle (NP) formulations on the pharmacokinetic, pharmacodynamic and biodistribution profiles of peptide- and protein-like drugs following oral administration is critically reviewed. The possible mechanisms of absorption enhancement and the effects of the physicochemical properties of the NP are examined. The potential advantages and challenges of physiologically-based pharmacokinetic (PBPK) modelling to help predict efficacy in man are discussed. The importance of developing and expanding the regulatory framework to help translate the technology into the clinic and accelerate the availability of oral nanoparticulate formulations is emphasized. In conclusion, opportunities for future work to improve the state of the art of oral nanomedicines are identified. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Antiretroviral Drug-Associated Oral Lichenoid Reaction in HIV Patient: A Case Report

    Directory of Open Access Journals (Sweden)

    Pratanporn Arirachakaran

    2010-01-01

    Full Text Available Antiretroviral therapy has changed the course of HIV disease and improved quality of life in HIV patients. Incidence of an oral lichenoid drug reaction induced by zidovudine is not common. Once it occurs, it affects a patient's well being, in particular their oral functions. Here we report the first case of a 34-year-old Thai man with painful erosive lesions involving the lip and buccal mucosa. Treatment with topical fluocinolone acetonide 0.1% alleviated the patient's oral pain, but it was not until the subsequent withdrawal of zidovudine that the patient showed improvement and resolution of the lesions. Long-term follow-up was useful in the management of this patient, and no recurrence of the lesion was found during 21-month follow-up in this patient.

  11. Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

    Directory of Open Access Journals (Sweden)

    Priya Bawa

    2011-12-01

    Full Text Available Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments.

  12. Antidiabetic Evaluation of Momordica charantia L Fruit Extracts

    Science.gov (United States)

    Tahira, S; Hussain, F

    2014-01-01

    To investigate hypoglycaemic, hypolipidaemic and pancreatic beta cell regeneration activities of Momordica charantia L fruits (MC). Alloxan-induced diabetic rabbits were treated with methanolic and ethanolic MC extract. Effects of plant extracts and the drug glibenclamide on serum glucose, lipid profile and pancreatic beta cell were determined after two weeks of treatment. Serum glucose and lipid profiles were assayed by kit methods. Pancreatic tissue histopathology was performed to study pancreatic beta cell regeneration. Momordica charantia extracts produced significant hypoglycaemic effects (p Momordica charantia supplementations were unable to normalize glucose and lipid profiles. Glibenclamide, a standard drug, not only lowered hyperglycaemia and hyperlipidaemia but also restored the normal levels. Regeneration of pancreatic beta cells by MC extracts was minimal, with fractional improvement produced by glibenclamide. The most significant finding of the present study was a 28% reduction in hyperglycaemia by MC ethanol extracts. To determine reliable antidiabetic potentials of MC, identification of the relevant antidiabetic components and underlying mechanisms is warranted. PMID:25429471

  13. Antidiabetic potential of Conocarpus lancifolius

    Directory of Open Access Journals (Sweden)

    Malik Saadullah

    2014-06-01

    Full Text Available The antidiabetic activity of Conocarpus lancifolius extract was investigated in vitro, as alpha glucosidase inhibition and in vivo as alloxan induced diabetic rabbits with other biochemical parameters (LDL, HDL, SGPT, SGOT, cretinine, urea and triglyceride. Alpha-glucosidase inhibition activity was performed by using acorbose as standred. Methanolic extract show alpha-glucosidase inhibition activity. The dose of 200 mg/kg body weight significantly (p<0.05 decreases the blood glucose level, plasma total cholesterol, triglycerides and LDL in treated rabbits as compared to diabetic rabbits. This dose significantly increased the level of HDL in treated group. The activity of SGOT and SGPT also significantly (p<0.05 decreased in treated diabetic rabbits. Phytochemical studies show the presence of glycosides, tannins, saponins and terpenoids. The antidiabetic potential is may be due to its saponin contents.

  14. Prevalence of drugs in oral fluid from truck drivers in Brazilian highways.

    Science.gov (United States)

    Bombana, Henrique Silva; Gjerde, Hallvard; Dos Santos, Marcelo Filonzi; Jamt, Ragnhild Elén Gjulem; Yonamine, Mauricio; Rohlfs, Waldo José Caram; Muñoz, Daniel Romero; Leyton, Vilma

    2017-03-01

    Traffic accidents are responsible for 1.25 million deaths worldwide and are the most common cause of death among those aged 15-29 years. In Brazil, traffic accidents caused more than 44,000 deaths in 2014. The use of psychoactive drugs is an important risk factor for being involved in traffic accidents. Previous studies have found that psychoactive substances are commonly used by truck drivers in Brazil to maintain their extensive work schedule and stay awake while driving during nighttime hours. The state of Sao Paulo is one of the most important states regarding goods transportation. Important highways cross through Sao Paulo to other regions from Brazil and to other countries in Latin America. This study aims to determine the prevalence of illicit drug use by truck drivers in the state of Sao Paulo through toxicological analyses of oral fluid. Truck drivers were randomly stopped by police officers on federal roads during morning hours. Oral fluid samples were collected using the Quantisal™ device. In addition, a questionnaire concerning sociodemographic characteristics and health information was administered. Oral fluid samples were screened for amphetamine, cocaine, and tetrahydrocannabinol (Δ9-THC) by ELISA and the confirmation was performed using ultra performance liquid chromatography with tandem mass spectrometry detection (UPLC-MS/MS). Of the 764 drivers stopped, 762 agreed to participate. The participants were driving an average of 614km and 9.4h a day. Of the total samples, 5.2% (n=40) tested positive for drugs. Cocaine was the most frequently found drug (n=21), followed by amphetamine (n=16) and Δ9-THC (n=8). All drivers were men with an average age of 42.5 years. With these results we were able to verify that many truck drivers were still consuming psychoactive drugs while driving, and cocaine was the most prevalent one. This reinforces the need for preventive measures aimed at controlling the use of illicit drugs by truck drivers in Brazil.

  15. REVIEW ON FLOATING DRUG DELIVERY SYSTEMS: AN APPROACH TO ORAL CONTROLLED DRUG DELIVERY VIA GASTRIC RETENTION

    Directory of Open Access Journals (Sweden)

    Kadam Shashikant M

    2011-06-01

    Full Text Available Controlled release (CR dosage forms have been extensively used to improve therapy with many important drugs. Several approaches are currently utilized in prolongation of gastric residence time, including floating drug delivery system, swelling and expanding system, polymeric bioadhesive system, modified shape system, high density system and other delayed gastric emptying devices. However, the development processes are faced with several physiological difficulties such as the inability to restrain and localize the system within the desired region of the gastrointestinal tract and the highly variable nature of the gastric emptying process. On the other hand, incorporation of the drug in a controlled release gastroretentive dosage forms (CR-GRDF which can remain in the gastric region for several hours would significantly prolong the gastric residence time of drugs and improve bioavailability, reduce drug waste, and enhance the solubility of drugs that are less soluble in high pH environment. Gastroretention would also facilitate local drug delivery to the stomach and proximal small intestine. Thus, gastroretention could help to provide greater availability of new products and consequently improved therapeutic activity and substantial benefits to patients. The purpose of this paper is to review the recent literature and current technology used in the development of gastroretentive dosage forms.

  16. Fast Dissolving Oral Film: A Novel and Innovative Drug Delivery system

    Directory of Open Access Journals (Sweden)

    Ankita Keshari

    2014-03-01

    Full Text Available The oral route is more suitable than other route of administration of therapeutic agents due to low cost of therapy and ease of administration and of patient compliance. This is noninvasive method and produce less side effect. There are some oral solid dosage forms like capsules and tablets. In geriatric, pediatric and dysphagia like patients find it difficult to swallow capsules and tablets and cannot take their medicines as prescribed manner. In some condition such as, sudden allergic attack, coughing, motion sickness, fear of choking and an unavailability of water, the swallowing of capsules or tablet or may become difficult. To overcome from these types of problem, the pharmaceutical industries are design and develop the new type of drug delivery system such as fast dissolving drug delivery systems. This innovative Oral fast dissolving film is a new dosage form in which a thin film is prepared by using hydrophilic polymers with suitable excipients. The film dissolved quickly in mouth without taking of water. The oral films are prepared by the solvent casting method or hot melt extrusion.

  17. Conjugates of degraded and oxidized hydroxyethyl starch and sulfonylureas: synthesis, characterization, and in vivo antidiabetic activity.

    Science.gov (United States)

    Abbas, Muhammad Azhar; Hameed, Shahid; Farman, Muhammad; Kressler, Jörg; Mahmood, Nasir

    2015-01-21

    Orally administered drugs usually face the problem of low water solubility, low permeability, and less retention in bloodstream leading to unsatisfactory pharmacokinetic profile of drugs. Polymer conjugation has attracted increasing interest in the pharmaceutical industry for delivering such low molecular weight (Mw) drugs as well as some complex compounds. In the present work, degraded and oxidized hydroxyethyl starch (HES), a highly biocompatible semisynthetic biopolymer, was used as a drug carrier to overcome the solubility and permeability problems. The HES was coupled with synthesized N-arylsulfonylbenzimidazolones, a class of sulfonylurea derivatives, by creating an amide linkage between the two species. The coupled products were characterized using GPC, FT-IR, (1)H NMR, and (13)C NMR spectroscopy. The experiments established the viability of covalent coupling between the biopolymer and N-arylsulfonylbenzimidazolones. The coupled products were screened for their in vivo antidiabetic potential on male albino rats. The coupling of sulfonylurea derivatives with HES resulted in a marked increase of the hypoglycemic activity of all the compounds. 2,3-Dihydro-3-(4-nitrobenzensulfonyl)-2-oxo-1H-benzimidazole coupled to HES10100 was found most potent with a 67% reduction in blood glucose level of the rats as compared to 41% reduction produced by tolbutamide and 38% by metformin.

  18. International Guidelines for Bioequivalence of Locally Acting Orally Inhaled Drug Products: Similarities and Differences

    OpenAIRE

    Lu, Dongmei; Lee, Sau L.; Lionberger, Robert A.; Choi, Stephanie; Adams, Wallace; Caramenico, Hoainhon N.; Chowdhury, Badrul A.; Conner, Dale P.; Katial, Rohit; Limb, Susan; Peters, John R.; Yu, Lawrence; Seymour, Sally; Li, Bing V.

    2015-01-01

    International regulatory agencies have developed recommendations and guidances for bioequivalence approaches of orally inhaled drug products (OIDPs) for local action. The objective of this article is to discuss the similarities and differences among these approaches used by international regulatory authorities when applications of generic and/or subsequent entry locally acting OIDPs are evaluated. We focused on four jurisdictions that currently have published related guidances for generic and...

  19. Oral health behavior of in-treatment female drug addicts in Tehran

    Directory of Open Access Journals (Sweden)

    Mehrdad Ghane

    2016-07-01

    Full Text Available Background and Aims: The aim of this study was to assess the oral health behaviors in women with addiction history. Materials and Methods: A cross-sectional study was carried out in women drug treatment centers under the supervision of Welfare Organization of Tehran province in Iran. Data collection process was conducted in three centers including a questionnaire with an interview format, clinical examination, and Chi-Square test and MANOVA for statistical analysis. Results: The mean age of 95 women participating in this study was less than forty, whereas the age of starting drugs was twenty two. A majority of the patients were unemployed (71% and more than that of two-third did not have a diploma education. Almost half of dentate participants had never or rarely brushed their teeth. Most of them had never used dental floss, while more than half had three or more times snacks or sweet drinks and more than three-fourth were daily smokers. The MANOVA analysis showed that the type of clinic to be visited, age, used stimulant, drug dependency length, the last time a dentist being visited and the brushing period had a statistically significant relationship with Decayed Teeth (DT, Missing Teeth (MT and Filled Teeth (FT (P<0.05. Conclusion: Women with the prior drug addiction history had an unpromising oral health status which was obvious in their self-perceived oral health. Taking the appropriate preventive and therapeutic actions aiming for promoting oral health status of them seems to be necessary.

  20. A new drug nanocrystal self-stabilized Pickering emulsion for oral delivery of silybin.

    Science.gov (United States)

    Yi, Tao; Liu, Chuan; Zhang, Jiao; Wang, Fan; Wang, Jirui; Zhang, Jifen

    2017-01-01

    A new silybin nanocrystal self-stabilized Pickering emulsion (SN-SSPE) has been developed using a high pressure homogenization method to improve the oral bioavailability of silybin. Influences of homogenization pressure and drug content on the formation of SN-SSPE were studied. The morphology, structure and size of Pickering emulsion droplets were characterized using a scanning electron micrograph, confocal laser scanning microscopy and atomic force microscopy. The stability, in vitro release and in vivo oral bioavailability of SN-SSPE were investigated. Results indicated that the particle size of silybin nanocrystals (SN-NC) decreased when homogenization pressure increased until 100MPa. When the content of silybin reached 300mg or above, a stable Pickering emulsion of silybin could be formed by sufficient SN-NC covering surfaces of oil droplets completely and thus self-stabilizing the Pickering emulsion. The emulsion droplet of SN-SSPE with the size of 27.3±3.1μm showed a core-shell structure consisting of a core of oil and a shell of SN-NC. SN-SSPE has shown high stability over 40days. The in vitro release rate of SN-SSPE was faster than silybin coarse powder and similar to silybin nanocrystalline suspension (SN-NCS). The peak concentration of silybin of SN-SSPE following intragastric administration in rats was increased by 2.5-fold and 3.6-fold compared with SN-NCS and silybin coarse powder, respectively. The AUC of SN-SSPE was increased by 1.6-fold and 4.0-fold compared with SN-NCS and silybin coarse powder, respectively. All these results showed that the Pickering emulsion of silybin could be stabilized by nanocrystals of silybin itself and increased the oral bioavailability of silybin. The drug nanocrystalline self-stabilized Pickering emulsion was a promising oral drug delivery system for poorly soluble drugs.

  1. Production of dosage forms for oral drug delivery by laminar extrusion of wet masses.

    Science.gov (United States)

    Müllers, Katrin C; Wahl, Martin A; Pinto, João F

    2013-08-01

    Laminar extrusion of wet masses was studied as a novel technology for the production of dosage forms for oral drug delivery. Extrusion was carried out with a ram extruder. Formulations contained either microcrystalline cellulose (MCC) or dicalcium phosphate (DCP) as diluent, hydroxypropyl methylcellulose (HPMC), lactose, and water. Extrudates were characterized for their tensile strength, Young's modulus of elasticity, water absorption, gel forming capacity, and release of two model drugs, coumarin (COU) and propranolol hydrochloride (PRO). Cohesive extrudates could be produced with both filling materials (MCC and DCP) when HPMC was included as a binder at low amounts (3.3-4.5% w/w dry weight). Employing more HPMC, the elasticity of the wet masses increased which resulted in distinct surface defects. For MCC, the maximum HPMC amount that could be included in the formulations (15% w/w dry weight) did not affect the mechanical properties or decrease the drug release significantly. For DCP extrudates, the maximally effective HPMC amount was 30% (w/w dry weight) with influence on both the mechanical properties and drug release. This study suggests that laminar extrusion of wet masses is a feasible technique for the production of dosage forms for oral drug delivery.

  2. Molecular and pharmacokinetic properties of 222 commercially available oral drugs in humans.

    Science.gov (United States)

    Sakaeda, T; Okamura, N; Nagata, S; Yagami, T; Horinouchi, M; Okumura, K; Yamashita, F; Hashida, M

    2001-08-01

    This study was performed to determine the exclusion criteria that differentiate poorly absorbed drugs from good drug candidates, and to accelerate drug development by exclusion of unnecessary assessment. The molecular and pharmacokinetic properties of 222 commercially available oral drugs were tabulated and their correlations were analyzed. The exclusion criteria obtained were 1) a molecular weight of more than 500, and 2) a ClogP value of more than 5. Exceptions to molecular weight criteria were compounds with a sugar moiety, high atomic weight, and large cyclic structure. It was also suggested that being a substrate for MDRI (P-glycoprotein) does not always result in poor bioavailability, and that drug development by chemical modification of a seed or lead compound with quantitative structure activity relationship analysis can result in lower bioavailability, higher bound fraction and lower urinary excretion, which would hamper later development processes and might result in considerable drug-drug interaction. The criteria should be adjusted according to the pharmacological profiles of the agents in question and depending on the estimated profit, but ignoring these criteria may result in a significant waste of time and money during drug development.

  3. Physicians' preferences for prescribing oral and intravenous anticancer drugs: a Discrete Choice Experiment.

    Science.gov (United States)

    Benjamin, Laure; Cotté, François-Emery; Philippe, Caroline; Mercier, Florence; Bachelot, Thomas; Vidal-Trécan, Gwenaëlle

    2012-04-01

    Although efficacy and tolerability are classical criteria for treatment choice, patient adherence and tariff issues related to novel oral anticancer drugs may also influence therapeutic decisions. We estimated the relative influence of efficacy, tolerability, expected adherence and route of administration of a chemotherapy treatment on 203 French physicians' preferences who participated in a Discrete Choice Experiment (DCE), a quantitative method used to elicit preferences. From a questionnaire with six scenarii, respondents had to choose between two treatments which differed with respect to these four attributes. Scenarii were first presented in a curative setting then in a palliative setting. Efficacy, tolerability and expected adherence had two modalities (good versus moderate) and route of administration had three modalities (intravenous (€286-379/session), oral with the current tariff (€28/consultation), oral with a hypothetical tariff (€114)). Efficacy was the reference criterion in choosing a treatment whatever the therapeutic goal (β: 2.114, padherence (β: 1.223, p=0.0001) were influent in curative setting while the route of administration was still predominant in palliative setting (β: 0.431, p<0.0001). Results suggest that economic considerations as well as therapeutic efficacy play a significant role in choosing a treatment. Preference for oral chemotherapy with a hypothetical tariff for a patient support programme should be considered for the development of therapeutic education and healthcare coordination, currently not taken into account in the tariff of oral chemotherapy. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Employment-based reinforcement of adherence to oral naltrexone treatment in unemployed injection drug users.

    Science.gov (United States)

    Dunn, Kelly E; Defulio, Anthony; Everly, Jeffrey J; Donlin, Wendy D; Aklin, Will M; Nuzzo, Paul A; Leoutsakos, Jeannie-Marie S; Umbricht, Annie; Fingerhood, Michael; Bigelow, George E; Silverman, Kenneth

    2013-02-01

    Oral naltrexone has high potential for use as a relapse prevention pharmacotherapy for opiate dependence yet suffers from notoriously poor adherence. This study evaluated whether entry to a therapeutic workplace could reinforce adherence with oral naltrexone. Opiate-dependent and cocaine-using injection drug users were detoxified, inducted onto oral naltrexone, and randomly assigned to a contingency (n = 35) or prescription (n = 32) group for a 26-week period. Contingency participants were required to ingest naltrexone under staff observation to gain access to the therapeutic workplace. Prescription participants received a take-home supply of naltrexone and could access the workplace independent of naltrexone ingestion. Primary outcome measures were percent of urine samples positive for naltrexone at 30-day assessments and negative for opiates and cocaine at 30-day assessments. Contingency participants provided significantly more urine samples that were positive for naltrexone compared with prescription participants (72% vs. 21%, p negative (71% vs. 60%, p = .19.) or cocaine-negative (56% vs. 53%, p = .82) samples in the contingency and prescription groups, respectively. Opiate-positive samples were significantly more likely to occur in conjunction with cocaine (p workplace significantly promoted adherence to oral naltrexone, and that the majority of opiate use occurred in conjunction with cocaine use, suggesting that untreated cocaine use may limit the effectiveness of oral naltrexone in promoting opiate abstinence.

  5. Administración de medicamentos por vía oral: Interacciones medicamento - alimento Oral drug administration: drug-food interactions

    Directory of Open Access Journals (Sweden)

    Nélida Barrueco

    2008-03-01

    Full Text Available Introducción: la vía oral de administración de medicamentos es la vía más cómoda, segura y económica. Sin embargo, pueden existir interacciones con otros fármacos o con alimentos que alteren la eficacia y seguridad de los mismos. Objetivo: desarrollar un programa de información dirigido a enfermeros y enfermeras sobre la administración de medicamentos por vía oral. Método: se seleccionan los medicamentos más utilizados en el área de cardiología pediátrica, revisándose para cada principio activo la administración en relación con alimentos o productos medicinales y otros aspectos relacionados con la administración por vía oral. Resultados: se elabora una tabla informativa sobre un total de 28 principios activos. Discusión: Los farmacéuticos de hospital se han integrado recientemente en los equipos multidisciplinares y desde esta posición tienen la oportunidad de desarrollar diferentes programas de atención farmacéutica, educación sanitaria e información encaminadas a prevenir problemas relacionados con los medicamentos, aumentar su uso seguro y disminuir los riesgos asociados a cualquier tratamiento farmacológico. Las prescripciones médicas generalmente no indican el horario y la forma de administración de los medicamentos, dejando a enfermeros y enfermeras la responsabilidad de su organización. Por esto deben estar informados de cómo y cuándo se deben administrar los medicamentos, lo que permite garantizar su uso seguro y disminuir los riesgos asociados al tratamiento.Background: The easiest, safest and cheapest way to administrate drugs is by mouth (PO. Nevertheless, there may be interactions, either with other drugs or with food, which can modify efficacy and security of the drug itself. Objective: the development of a nursing information program about the administration of drugs PO. Method: we selected the most used drugs corresponding to the pediatric cardiology area, looking for the best administration

  6. Enhancement of oral bioavailability of cyclosporine A: comparison of various nanoscale drug-delivery systems

    Directory of Open Access Journals (Sweden)

    Wang K

    2014-10-01

    Full Text Available Kai Wang,1–3 Jianping Qi,1 Tengfei Weng,1,2 Zhiqiang Tian,1 Yi Lu,1 Kaili Hu,4 Zongning Yin,2 Wei Wu1 1School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education, Shanghai, People’s Republic of China; 2West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Tropical Crops Genetic Resources Institute, Hainan Provincial Engineering Research Center for Blumea Balsamifera, Chinese Academy of Tropical Agricultural Sciences, Danzhou, Hainan, People’s Republic of China; 4Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaAbstract: A variety of nanoscale delivery systems have been shown to enhance the oral absorption of poorly water-soluble and poorly permeable drugs. However, the performance of these systems has seldom been evaluated simultaneously. The aim of this study was to compare the bioavailability enhancement effect of lipid-based nanocarriers with poly(lactic-co-glycolic acid (PLGA nanoparticles (NPs to highlight the importance of the lipid composition, with cyclosporine A (CyA as a model drug. CyA-loaded PLGA NPs, nanostructured lipid carriers (NLCs, and self-microemulsifying drug-delivery systems (SMEDDS were prepared. The particle size of PLGA NPs (182.2±12.8 nm was larger than that of NLCs (89.7±9.0 nm and SMEDDS (26.9±1.9 nm. All vehicles are charged negatively. The entrapment efficiency of PLGA NPs and NLCs was 87.6%±1.6% and 80.3%±0.6%, respectively. In vitro release tests indicated that the cumulative release of CyA was lower than 4% from all vehicles, including Sandimmun Neoral®, according to the dialysis method. Both NLCs and SMEDDS showed high relative oral bioavailability, 111.8% and 73.6%, respectively, after oral gavage administration to beagle dogs, which was not statistically different from commercial Sandimmun Neoral®. However, PLGA NPs

  7. Role of Self-Association and Supersaturation in Oral Absorption of a Poorly Soluble Weakly Basic Drug.

    Science.gov (United States)

    Narang, Ajit S; Badawy, Sherif; Ye, Qingmei; Patel, Dhaval; Vincent, Maria; Raghavan, Krishnaswamy; Huang, Yande; Yamniuk, Aaron; Vig, Balvinder; Crison, John; Derbin, George; Xu, Yan; Ramirez, Antonio; Galella, Michael; Rinaldi, Frank A

    2015-08-01

    Precipitation of weakly basic drugs in intestinal fluids can affect oral drug absorption. In this study, the implications of self-association of brivanib alaninate in acidic aqueous solution, leading to supersaturation at basic pH condition, on its solubility and oral absorption were investigated. Self-association of brivanib alaninate was investigated by proton NMR spectroscopy, surface tension measurement, dynamic light scattering, isothermal titration calorimetry, and molecular modeling. Drug solubility was determined in various pH media, and its tendency to supersaturate upon pH shift was investigated in buffered and biorelevant aqueous solutions. Pharmacokinetic modeling of human oral drug absorption was utilized for parameter sensitivity analyses of input variables. Brivanib alaninate exhibited continuous, and pH- and concentration-dependent self-association. This phenomenon resulted in positive deviation of drug solubility at acidic pH and the formation of a stable supersaturated drug solution in pH-shift assays. Consistent with the supersaturation phenomenon observed in vitro, oral absorption simulations necessitated invoking long precipitation time in the intestine to successfully predict in vivo data. Self-association of a weakly basic drug in acidic aqueous solution can increase its oral absorption by supersaturation and precipitation resistance at the intestinal pH. This consideration is important to the selection of parameters for oral absorption simulation.

  8. Enhancing the Solubility and Oral Bioavailability of Poorly Water-Soluble Drugs Using Monoolein Cubosomes.

    Science.gov (United States)

    Ali, Md Ashraf; Kataoka, Noriko; Ranneh, Abdul-Hackam; Iwao, Yasunori; Noguchi, Shuji; Oka, Toshihiko; Itai, Shigeru

    2017-01-01

    Monoolein cubosomes containing either spironolactone (SPI) or nifedipine (NI) were prepared using a high-pressure homogenization technique and characterized in terms of their solubility and oral bioavailability. The mean particle size, polydispersity index (PDI), zeta potential, solubility and encapsulation efficiency (EE) values of the SPI- and NI-loaded cubosomes were determined to be 90.4 nm, 0.187, -13.4 mV, 163 µg/mL and 90.2%, and 91.3 nm, 0.168, -12.8 mV, 189 µg/mL and 93.0%, respectively, which were almost identical to those of the blank cubosome. Small-angle X-ray scattering analyses confirmed that the SPI-loaded, NI-loaded and blank cubosomes existed in the cubic space group Im3̄m. The lattice parameters of the SPI- and NI-loaded cubosomes were 147.6 and 151.6 Å, respectively, making them almost identical to that of blank cubosome (151.0 Å). The in vitro release profiles of the SPI- and NI-loaded cubosomes showed that they released less than 5% of the drugs into various media over 12-48 h, indicating that most of the drug remained encapsulated within the cubic phase of their lipid bilayer. Furthermore, the in vivo pharmacokinetic results suggested that these cubosomes led to a considerable increase in the systemic oral bioavailability of the drugs compared with pure dispersions of the same materials. Notably, the stability results indicated that the mean particle size and PDI values of these cubosomes were stable for at least 4 weeks. Taken together, these results demonstrate that monoolein cubosomes represent promising drug carriers for enhancing the solubility and oral bioavailability of poorly water-soluble drugs.

  9. Evaluation of an In Silico PBPK Post-Bariatric Surgery Model through Simulating Oral Drug Bioavailability of Atorvastatin and Cyclosporine

    OpenAIRE

    2013-01-01

    An increasing prevalence of morbid obesity has led to dramatic increases in the number of bariatric surgeries performed. Altered gastrointestinal physiology following surgery can be associated with modified oral drug bioavailability (F oral). In the absence of clinical data, an indication of changes to F oral via systems pharmacology models would be of value in adjusting dose levels after surgery. A previously developed virtual “post-bariatric surgery” population was evaluated through mimicki...

  10. Glycemic control and cost-effectiveness attained by the drug utilization of oral antidiabetic agents in a tertiary care hospital in South India

    OpenAIRE

    Nirmal George; Ajith Kumar PV; Vijayalekshmi Amma S.

    2016-01-01

    Background: Diabetes mellitus require lifelong intervention and Kerala has high prevalence. New expensive agents require comparison with existing regimens for cost-effectiveness. Methods: Socio-demographic, anthropometric, FPG and HbA1C (baseline and post treatment) of 150 patients (73 men; 77 women) were obtained from records using standard case report forms in our retrospective study. ANOVA and paired t test were used for between groups and within group comparison. Results: Metformin ...

  11. Drug repurposing: a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Hanna M Vesterinen

    Full Text Available To develop and implement an evidence based framework to select, from drugs already licenced, candidate oral neuroprotective drugs to be tested in secondary progressive multiple sclerosis.Systematic review of clinical studies of oral putative neuroprotective therapies in MS and four other neurodegenerative diseases with shared pathological features, followed by systematic review and meta-analyses of the in vivo experimental data for those interventions. We presented summary data to an international multi-disciplinary committee, which assessed each drug in turn using pre-specified criteria including consideration of mechanism of action.We identified a short list of fifty-two candidate interventions. After review of all clinical and pre-clinical evidence we identified ibudilast, riluzole, amiloride, pirfenidone, fluoxetine, oxcarbazepine, and the polyunsaturated fatty-acid class (Linoleic Acid, Lipoic acid; Omega-3 fatty acid, Max EPA oil as lead candidates for clinical evaluation.We demonstrate a standardised and systematic approach to candidate identification for drug rescue and repurposing trials that can be applied widely to neurodegenerative disorders.

  12. Novel Nanostructured Solid Materials for Modulating Oral Drug Delivery from Solid-State Lipid-Based Drug Delivery Systems.

    Science.gov (United States)

    Dening, Tahnee J; Rao, Shasha; Thomas, Nicky; Prestidge, Clive A

    2016-01-01

    Lipid-based drug delivery systems (LBDDS) have gained significant attention in recent times, owing to their ability to overcome the challenges limiting the oral delivery of poorly water-soluble drugs. Despite the successful commercialization of several LBDDS products over the years, a large discrepancy exists between the number of poorly water-soluble drugs displaying suboptimal in vivo performances and the application of LBDDS to mitigate their various delivery challenges. Conventional LBDDS, including lipid solutions and suspensions, emulsions, and self-emulsifying formulations, suffer from various drawbacks limiting their widespread use and commercialization. Accordingly, solid-state LBDDS, fabricated by adsorbing LBDDS onto a chemically inert solid carrier material, have attracted substantial interest as a viable means of stabilizing LBDDS whilst eliminating some of the various limitations. This review describes the impact of solid carrier choice on LBDDS performance and highlights the importance of appropriate solid carrier material selection when designing hybrid solid-state LBDDS. Specifically, emphasis is placed on discussing the ability of the specific solid carrier to modulate drug release, control lipase action and lipid digestion, and enhance biopharmaceutical performance above the original liquid-state LBDDS. To encourage the interested reader to consider their solid carrier choice on a higher level, various novel materials with the potential for future use as solid carriers for LBDDS are described. This review is highly significant in guiding future research directions in the solid-state LBDDS field and fostering the translation of these delivery systems to the pharmaceutical marketplace.

  13. Cellulose nanofiber aerogel as a promising biomaterial for customized oral drug delivery

    Directory of Open Access Journals (Sweden)

    Bhandari J

    2017-03-01

    Full Text Available Jyoti Bhandari,1 Harshita Mishra,1 Pawan Kumar Mishra,2 Rupert Wimmer,2,3 Farhan J Ahmad,1 Sushama Talegaonkar1 1Department of Pharmaceutics, Jamia Hamdard, New Delhi, India; 2Department of Wood Science, Mendel University in Brno, Brno, Czech Republic; 3Institute for Natural Materials Technology, Department of Agrobiotechnology, IFA-Tulln, University of Natural Resources and Life Sciences, Vienna, Austria Abstract: Cellulose nanofiber (CNF aerogels with favorable floatability and mucoadhesive properties prepared by the freeze-drying method have been introduced as new possible carriers for oral controlled drug delivery system. Bendamustine hydrochloride is considered as the model drug. Drug loading was carried out by the physical adsorption method, and optimization of drug-loaded formulation was done using central composite design. A very lightweight-aerogel-with-matrix system was produced with drug loading of 18.98%±1.57%. The produced aerogel was characterized for morphology, tensile strength, swelling tendency in media with different pH values, floating behavior, mucoadhesive detachment force and drug release profiles under different pH conditions. The results showed that the type of matrix was porous and woven with excellent mechanical properties. The drug release was assessed by dialysis, which was fitted with suitable mathematical models. Approximately 69.205%±2.5% of the drug was released in 24 hours in medium of pH 1.2, whereas ~78%±2.28% of drug was released in medium of pH 7.4, with floating behavior for ~7.5 hours. The results of in vivo study showed a 3.25-fold increase in bioavailability. Thus, we concluded that CNF aerogels offer a great possibility for a gastroretentive drug delivery system with improved bioavailability. Keywords: cellulose nanofiber, aerogel, controlled release, gastroretentive, floating behavior, swelling behavior, mucoadhesion, bioavailability

  14. Oral hygiene products, medications and drugs - hidden aetiological factors for dental erosion.

    Science.gov (United States)

    Hellwig, Elmar; Lussi, Adrian

    2014-01-01

    Acidic or EDTA-containing oral hygiene products and acidic medicines have the potential to soften dental hard tissues. The low pH of oral care products increases the chemical stability of some fluoride compounds and favours the incorporation of fluoride ions in the lattice of hydroxyapatite and the precipitation of calcium fluoride on the tooth surface. This layer has some protective effect against an erosive attack. However, when the pH is too low or when no fluoride is present these protecting effects are replaced by direct softening of the tooth surface. Oral dryness can occur as a consequence of medication such as tranquilizers, antihistamines, antiemetics and antiparkinsonian medicaments or of salivary gland dysfunction. Above all, patients should be aware of the potential demineralization effects of oral hygiene products with low pH. Acetyl salicylic acid taken regularly in the form of multiple chewable tablets or in the form of headache powder, as well as chewing hydrochloric acids tablets for the treatment of stomach disorders, can cause erosion. There is most probably no direct association between asthmatic drugs and erosion on the population level. Consumers and health professionals should be aware of the potential of tooth damage not only by oral hygiene products and salivary substitutes but also by chewable and effervescent tablets. Several paediatric medications show a direct erosive potential in vitro. Clinical proof of the occurrence of erosion after use of these medicaments is still lacking. However, regular and prolonged use of these medicaments might bear the risk of causing erosion. Additionally, it can be assumed that patients suffering from xerostomia should be aware of the potential effects of oral hygiene products with low pH and high titratable acidity.

  15. Provisional in-silico biopharmaceutics classification (BCS) to guide oral drug product development.

    Science.gov (United States)

    Wolk, Omri; Agbaria, Riad; Dahan, Arik

    2014-01-01

    The main objective of this work was to investigate in-silico predictions of physicochemical properties, in order to guide oral drug development by provisional biopharmaceutics classification system (BCS). Four in-silico methods were used to estimate LogP: group contribution (CLogP) using two different software programs, atom contribution (ALogP), and element contribution (KLogP). The correlations (r(2)) of CLogP, ALogP and KLogP versus measured LogP data were 0.97, 0.82, and 0.71, respectively. The classification of drugs with reported intestinal permeability in humans was correct for 64.3%-72.4% of the 29 drugs on the dataset, and for 81.82%-90.91% of the 22 drugs that are passively absorbed using the different in-silico algorithms. Similar permeability classification was obtained with the various in-silico methods. The in-silico calculations, along with experimental melting points, were then incorporated into a thermodynamic equation for solubility estimations that largely matched the reference solubility values. It was revealed that the effect of melting point on the solubility is minor compared to the partition coefficient, and an average melting point (162.7 °C) could replace the experimental values, with similar results. The in-silico methods classified 20.76% (± 3.07%) as Class 1, 41.51% (± 3.32%) as Class 2, 30.49% (± 4.47%) as Class 3, and 6.27% (± 4.39%) as Class 4. In conclusion, in-silico methods can be used for BCS classification of drugs in early development, from merely their molecular formula and without foreknowledge of their chemical structure, which will allow for the improved selection, engineering, and developability of candidates. These in-silico methods could enhance success rates, reduce costs, and accelerate oral drug products development.

  16. Recent developments in the use of bioadhesive systems for delivery of drugs to the oral cavity.

    Science.gov (United States)

    Smart, John D

    2004-01-01

    The delivery of therapeutic agents to, or via, the oral cavity is limited by the efficient removal mechanisms that exist in this area. Bioadhesive formulations have been developed to allow prolonged localized therapy and enhanced systemic delivery. The oral mucosa however, while avoiding first-pass effects, is a formidable barrier to drug absorption, especially for "biopharmaceutical" products arising from the recent innovations in genomics and proteomics. Bioadhesive polymers are typically hydrophilic macromolecules containing numerous hydrogen-bonding groups. Second-generation bioadhesives include modified or new polymers that allow enhanced adhesion and/or drug delivery, along with site-specific ligands such as lectins. Over the last 20 years, a range of bioadhesive formulations have been developed for the oral cavity, but only comparatively few have found their way onto the market. This review will consider some recent developments in the use of bioadhesive buccal systems, notably the development of new polymers, advanced delivery systems, and the exploitation of the multifunctional properties of some bioadhesives.

  17. Non-Oral Drug Delivery Strategies: From Early Diagnosis to Advanced Treatments

    Directory of Open Access Journals (Sweden)

    Claudia Trenkwalder

    2015-08-01

    Full Text Available This educational symposium, sponsored by Britannia Pharmaceuticals Limited, was held during the 1st Congress of the European Academy of Neurology (EAN, which took place from 20th-23rd June 2015 in Berlin, Germany. The symposium reviewed the role of non-oral drug delivery strategies in patients with Parkinson’s disease (PD and how they can overcome problems that occur with the gastrointestinal (GI route of administration in many patients. GI dysfunction is recognised as a common problem in PD and may in fact be a preclinical marker of the disease. It can affect the absorption of oral medication resulting in OFF periods and unreliable control of motor symptoms, which in turn can have a negative impact on quality of life (QoL. Delayed time-to-ON (TTO after an oral levodopa dose and dose failures are known to be significant contributors to total OFF time. Results of the recently completed AM-IMPAKT trial in patients with morning akinesia due to a delay in the onset of oral levodopa effect demonstrate that apomorphine intermittent injection (penject is able to provide rapid and effective resolution of such complications, restoring patients to the ON state quickly and allowing them to get on with their daily activities.

  18. Analytical evaluation of four on-site oral fluid drug testing devices.

    Science.gov (United States)

    Vanstechelman, Sylvie; Isalberti, Cristina; Van der Linden, Trudy; Pil, Kristof; Legrand, Sara-Ann; Verstraete, Alain G

    2012-03-01

    The use of oral fluid (OF) as an alternative matrix for the detection of drugs of abuse has increased over the last decade, leading to the need for a rapid, simple, and reliable on-site OF testing device. Four on-site OF drug testing devices (Dräger DrugTest 5000, Cozart DDS, Mavand Rapid STAT, and Innovacon OrAlert) were evaluated on 408 volunteers at drug treatment centers. UPLC-MS-MS results were used as reference to determine sensitivity, specificity and accuracy for each device, applying Belgian legal confirmation cutoffs for benzoylecgonine, cocaine, and THC (10 ng/mL); morphine and 6-acetylmorphine (5 ng/mL); and amphetamine and 3,4-methylenedioxymethylamphetamine (25 ng/mL). Sensitivity for cocaine was 50%, 50%, 27%, and 11% for DrugTest, OrAlert, Rapid STAT, and DDS 806, respectively. For opiates, sensitivities were 84%, 73%, 77%, and 65%, respectively. For THC, the sensitivities were 81%, 23%, 43%, and 28%, respectively. For amphetamines, the sensitivities were 75%, 33%, 17%, and 67%, respectively. Specificity was >88% for opiates and THC, > 90% for amphetamines, and > 97% for cocaine. All tests showed good specificity. DrugTest had the highest sensitivity, although it was still low for some analytes.

  19. Anti-diabetic potential of chloroform extract of flowers of Calotropis gigantea: An in vitro and in vivo study

    Directory of Open Access Journals (Sweden)

    N K Choudhary

    2011-01-01

    Full Text Available The chloroform extract of Calotropis gigantea flowers was evaluated for anti-diabetic activity in alloxan-induced hyperglycemia in vivo and inhibition of α-amylase and α-glucosidase in vitro. It was also intended to establish correlation between the serum marker antioxidant enzymes and diabetes. Diabetes was induced by a single intraperitoneal injection of alloxan monohydrate freshly prepared in a dose of 150 mg/kg. Chloroform extract showing presence of flavonoids was administered orally at the doses of 100 and 200 mg/kg for 21 consecutive days. Fasting blood glucose level, glycosylated haemoglobin, blood glutathione, serum creatinine kinase, serum lactate dehydrogenase levels as well as final change in body weight were evaluated. In vitro inhibition of carbohydrate digestive enzymes (α-amylase and α-glucosidase was also determined. Experimental findings showed moderately significant anti-diabetic potential of extract in terms of reduction of fasting glucose level in diabetic rats. The extract was found statistically significant in maintaining the level of serum marker antioxidant enzymes. Overall, the effect of chloroform extract particularly 200 mg/kg was moderate as compared to that of standard drug glibenclamide.

  20. Characterization of the Antidiabetic Role of Parkinsonia aculeata (Caesalpineaceae

    Directory of Open Access Journals (Sweden)

    Ana Catarina Rezende Leite

    2011-01-01

    Full Text Available This paper reports the characterization of the antidiabetic role of a hydroethanolic extract from Parkinsonia aerial parts (HEPA, in normal and alloxan-induced diabetic rats, treated with HEPA (125 and 250 mg/kg; p.o.. Oral glucose tolerance test, acute oral toxicity test and preliminary phytochemical analyses were performed. The diabetic rats treated with HEPA showed a significant reduction in serum and urinary glucose, urinary urea and triglyceride levels, as compared to the diabetic untreated group. However, in the normal treated groups, a significant reduction was found only in serum triglyceride levels. In all treated diabetic groups, an improvement in hepatic glycogen was observed, as well as a decrease in liquid intake and urinary volume, and an enhancement in the weight of skeletal muscles (soleus and extensor digitorum longus, kidneys and epididymal adipose tissue. Nevertheless, body and liver weights were ameliorated only in the diabetic group treated with HEPA (250 mg/kg. Moreover, oral glucose tolerance was higher in animals treated with HEPA, while results also showed that HEPA could be considered toxicologically safe. Phytochemical analysis revealed the presence of tanins, flavonoids and steroids in HEPA. In conclusion, P. aculeata presents an antidiabetic activity and other beneficial effects that ameliorate diabetes and associated complications.

  1. [Tissue and cell interactions in the oral mucosa after cytostatic drugs administration].

    Science.gov (United States)

    Bykov, V L; Leont'eva, I V

    2011-01-01

    In the preceding work ("Morphology", 2011, issue 2), the regularities of oral mucosal (OM) epithelium injury after the cytostatic drug (CSD) treatment and its further regeneration, were reviewed. This paper presents the systematized summary of current literature data and the authors' own findings on the regularities of CSD effect on non-epithelial OM cell populations and their interactions with each other and the epithelium. The changes of intraepithelial tissue homeostasis, associated with CSD effect on intraepithelial lymphocytes, granulocytes, dendritic antigen presenting cells and melanocytes, interacting with epitheliocytes, are described. The data are presented, indicating that along with the epithelium, the cell populations of lamina propria and submucosal connective tissue, as well as the small blood vessels, are important targets of CSD in the OM tissues. The concept of a unifying model, describing tissue, cellular and molecular mechanisms of the oral mucositis development after CSD treatment, is reviewed.

  2. Prescribing of Antidiabetic Medicines before, during and after Pregnancy

    DEFF Research Database (Denmark)

    Charlton, Rachel A.; Klungsøyr, Kari; Neville, Amanda J.;

    2016-01-01

    Aim: To explore antidiabetic medicine prescribing to women before, during and after pregnancy in different regions of Europe. Methods: A common protocol was implemented across seven databases in Denmark, Norway, The Netherlands, Italy (Emilia Romagna/Tuscany), Wales and the rest of the UK. Women ...... in the treatment of gestational diabetes despite international guidelines....... and 88.8% in the Netherlands received an insulin analogue alone or in combination with human insulin, this proportion increasing over time. Oral products were mainly metformin and prescribing was highest in the 3 months before pregnancy. Metformin use during pregnancy increased in some countries...

  3. The oral health of street-recruited injecting drug users: prevalence and correlates of problems.

    Science.gov (United States)

    Laslett, Anne-Marie; Dietze, Paul; Dwyer, Robyn

    2008-11-01

    To examine the effects of a series of injecting drug users' (IDU) characteristics and drug use behaviours upon the self-reported oral health of a sample of IDU. Cross-sectional survey. Melbourne, Australia. A total of 285 IDU recruited through needle and syringe programmes, snowballing and outreach across six sites. Structured survey that collected information on current drug use patterns, self-reported blood-borne virus status and general health factors, including open-ended questions on past-year dental health problems. Sixty-eight per cent of the sample reported dental problems that were commonly severe and caused dental pain. Despite these reported problems, almost half the sample had not visited the dentist in the 12 months prior to the survey. Participants who were older, and reported homelessness, not eating every day and more common injection of amphetamines rather than heroin in the previous month, were more likely to report having a past-year dental problem. Dental problems in IDUs are common but few receive treatment. Further, those using amphetamines, with poor housing, hygiene and poor nutrition, are most at risk. Programmes designed to improve the oral health of IDU need to be developed and implemented in a manner amenable to the varying social circumstances of this marginalized group in the community.

  4. Goblet cell targeting nanoparticle containing drug-loaded micelle cores for oral delivery of insulin.

    Science.gov (United States)

    Zhang, Peiwen; Xu, Yining; Zhu, Xi; Huang, Yuan

    2015-12-30

    Oral administration of insulin remains a challenge due to its poor enzymatic stability and inefficient permeation across epithelium. We herein developed a novel self-assembled polyelectrolyte complex nanoparticles by coating insulin-loaded dodecylamine-graft-γ-polyglutamic acid micelles with trimethyl chitosan (TMC). The TMC material was also conjugated with a goblet cell-targeting peptide to enhance the affinity of nanoparticles with epithelium. The developed nanoparticle possessed significantly enhanced colloid stability, drug protection ability and ameliorated drug release profile compared with graft copolymer micelles or ionic crosslinked TMC nanoparticles. For in vitro evaluation, Caco-2/HT29-MTX-E12 cell co-cultures, which composed of not only enterocyte-like cells but also mucus-secreting cells and secreted mucus layer, were applied to mimic the epithelium. Intracellular uptake and transcellular permeation of encapsulated drug were greatly enhanced for NPs as compared with free insulin or micelles. Goblet cell-targeting modification further increased the affinity of NPs with epithelium with changed cellular internalization mechanism. The influence of mucus on the cell uptake was also investigated. Ex vivo performed with rat mucosal tissue demonstrated that the nanoparticle could facilitate the permeation of encapsulated insulin across the intestinal epithelium. In vivo study preformed on diabetic rats showed that the orally administered nanoparticles elicited a prolonged hypoglycemic response with relative bioavailability of 7.05%.

  5. Size-exclusive effect of nanostructured lipid carriers on oral drug delivery.

    Science.gov (United States)

    Li, Huipeng; Chen, Minglei; Su, Zhigui; Sun, Minjie; Ping, Qineng

    2016-09-10

    Nanostructured lipid carriers (NLCs) are generally recognized as safe (GRAS) to form a controlled nanostructure are a new generation of lipid nanoparticles. In addition to formulation and particle surface properties, particle size had great influence for overcoming gastrointestinal (GI) barriers on the oral drug delivery of lipid based nanoparticles. In the present study, we investigated the effect of size on oral drug delivery for NLCs. The NLCs with different particle sizes (NLCs100nm, NLCs200nm and NLCs300nm) were prepared by using solvent evaporation method and the coumarin-6 (C6) or DiO/DiI was loaded in the nanoparticles as the fluorescence probe. The MTT assay indicated that both blank NLCs and C6-loaded NLCs displayed relatively low toxicity towards Caco-2 cells. Cellular uptake mechanisms of NLCs with different sizes were found to be similar and governed by active endocytosis, clathrin- and caveolae-mediated process. However, the smaller nanoparticle (NLC-100nm) showed higher uptake efficiency in Caco-2 cell (Poral administration. NLC-100nm exhibited the most stability according to the most stable FRET signal. In situ rat intestinal absorption experiments and in vitro ligated rat intestinal loops model demonstrated that all NLCs could rapidly penetrate duodenum versus jejunum, ileum and colon (Poral drug delivery of lipid based nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Identification of PPARgamma partial agonists of natural origin (II: in silico prediction in natural extracts with known antidiabetic activity.

    Directory of Open Access Journals (Sweden)

    Laura Guasch

    Full Text Available BACKGROUND: Natural extracts have played an important role in the prevention and treatment of diseases and are important sources for drug discovery. However, to be effectively used in these processes, natural extracts must be characterized through the identification of their active compounds and their modes of action. METHODOLOGY/PRINCIPAL FINDINGS: From an initial set of 29,779 natural products that are annotated with their natural source and using a previously developed virtual screening procedure (carefully validated experimentally, we have predicted as potential peroxisome proliferators-activated receptor gamma (PPARγ partial agonists 12 molecules from 11 extracts known to have antidiabetic activity. Six of these molecules are similar to molecules with described antidiabetic activity but whose mechanism of action is unknown. Therefore, it is plausible that these 12 molecules could be the bioactive molecules responsible, at least in part, for the antidiabetic activity of the extracts containing them. In addition, we have also identified as potential PPARγ partial agonists 10 molecules from 16 plants with undescribed antidiabetic activity but that are related (i.e., they are from the same genus to plants with known antidiabetic properties. None of the 22 molecules that we predict as PPARγ partial agonists show chemical similarity with a group of 211 known PPARγ partial agonists obtained from the literature. CONCLUSIONS/SIGNIFICANCE: Our results provide a new hypothesis about the active molecules of natural extracts with antidiabetic properties and their mode of action. We also suggest plants with undescribed antidiabetic activity that may contain PPARγ partial agonists. These plants represent a new source of potential antidiabetic extracts. Consequently, our work opens the door to the discovery of new antidiabetic extracts and molecules that can be of use, for instance, in the design of new antidiabetic drugs or functional foods focused

  7. 21 CFR 310.529 - Drug products containing active ingredients offered over-the-counter (OTC) for oral use as insect...

    Science.gov (United States)

    2010-04-01

    ... offered over-the-counter (OTC) for oral use as insect repellents. 310.529 Section 310.529 Food and Drugs... ingredients offered over-the-counter (OTC) for oral use as insect repellents. (a) Thiamine hydrochloride... insect repellent (an orally administered drug product intended to keep insects away). There is a lack...

  8. Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation.

    Science.gov (United States)

    Zhang, Xingwang; Chen, Guijiang; Zhang, Tianpeng; Ma, Zhiguo; Wu, Baojian

    2014-01-01

    Lipid nanocarriers are becoming a versatile platform for oral delivery of lipophilic drugs. In this article, we aimed to explore the gastrointestinal behaviors of lipid nanoparticles and the effect of PEGylation on oral absorption of fenofibrate (FN), a Biopharmaceutics Classification System (BCS) II model drug. FN-loaded PEGylated lipid nanoparticles (FN-PLNs) were prepared by the solvent-diffusion method and characterized by particle size distribution, morphology, Fourier transform infrared spectroscopy, and drug release. Lipolytic experiments were performed to assess the resistance of lipid nanoparticles against pancreatic lipase. Pharmacokinetics was evaluated in rats after oral administration of FN preparations. The obtained FN-PLNs were 186.7 nm in size with an entrapment efficiency of >95%. Compared to conventional lipid nanoparticles, PLNs exhibited slower drug release in the lipase-containing medium, strikingly reduced mucin binding, and suppressed lipolysis in vitro. Further, oral absorption of FN was significantly enhanced using PLNs with relative bioavailability of 123.9% and 157.0% to conventional lipid nanoparticles and a commercial formulation (Lipanthyl(®)), respectively. It was demonstrated that reduced mucin trapping, suppressed lipolysis, and/or improved mucosal permeability were responsible for increased oral absorption. These results facilitated a better understanding of the in vivo fate of lipid nanoparticles, and suggested the potential of PLNs as oral carriers of BCS II drugs.

  9. Potential antidiabetic effect of the Semecarpus anacardium in a type 2 diabetic rat model.

    Science.gov (United States)

    Khan, Haseena Banu Hedayathullah; Vinayagam, Kaladevi Siddhi; Renny, Chris Maria; Palanivelu, Shanthi; Panchanadham, Sachdanandam

    2013-02-01

    Semecarpus anacardium Linn. nut milk extract (SA) was evaluated for its antidiabetic role in type 2 diabetic rats. Type 2 diabetes was induced in rats by feeding high-fat diet for 2 weeks followed by single intraperitoneal injection of streptozotocin 35 mg/kg body weight. Diabetic rats were treated with SA orally at a dosage of 200 mg/kg body weight daily for 30 days. Metformin (500 mg/kg body weight, orally) was used as a reference drug. SA significantly (p < 0.05) reduced the blood glucose levels and decreased the levels of HbA1c and the glucose intolerance. SA treatment significantly (p < 0.05) decreased the increase in lipid profile. The levels of urea, uric acid and creatinine were restored to near normal levels when compared with control diabetic rats. The histopathological abnormalities were also found to be normalized after treatment with SA nut milk extract. The potential antihyperglycemic action of SA is plausibly due to its underlying antioxidant role.

  10. Thermal analysis of some antidiabetic pharmaceutical compounds.

    Science.gov (United States)

    Attia, Ali Kamal; Ibrahim, Magda Mohamed; El-Ries, Mohamed Abdel-Nabi

    2013-01-01

    Thermal behavior of some antidiabetic drugs such as pioglitazone hydrochloride (PTZ), rosiglitazone maleate (RGZ), glibenclamide (GBD) and glimepiride (GMP) has been studied. Thermogravimetric analysis (TGA), derivative thermogravimetry (DTG) and differential thermal analysis (DTA) techniques were used to study the thermal behavior of the drugs under investigation. Thermal analysis technique was used to obtain quality control parameters such as melting point 193.13 °C, 122.42 °C, 173.75 °C and 208 °C for PTZ, RGZ, GBD and GMP, respectively. The values of melting point of gave satisfactory results in comparison to that obtained by using the official method. Non-isothermal methods were employed to determine the activation energy values of the first stage of thermal decomposition. Comparison of the activation energy values suggests the following sequence of thermal stability: GMP > GBD > RGZ > PTZ. The results obtained are useful for the identification of these compounds and permitted interpretations concerning their thermal decomposition. Thermal stability of pharmaceutical compounds can be studied and compared by using thermal analysis techniques.

  11. An overview of herbal supplement utilization with particular emphasis on possible interactions with dental drugs and oral manifestations.

    Science.gov (United States)

    Abebe, Worku

    2003-01-01

    Herbal medication in the United States is a popular form of therapy. This paper provides an overview of the utilization of herbal supplements with particular emphasis on possible interactions with oral health drugs and oral manifestations. Herbal supplements are regulated by the Dietary Supplement Health and Education Act (DSHEA), which limits their regulation by the U.S Food and Drug Administration (FDA). A number of studies indicate that there is a progressive increase in the utilization of herbal supplements. The majority of consumers of these products are white, middle-aged women who have some college education. Many of the consumers use pharmaceutical drugs concurrently, but most do not inform their health-care providers about their use of herbal supplements. Various herbal supplements have been reported or are suspected to interact with certain oral health drugs, the most important one being 1) bromelain, cayenne, chamomile, feverfew, dong quai, eleuthro/Seberian ginseng, garlic, ginkgo, ginger, ginseng and licorice interacting with aspirin; 2) aloe latex, ephedra, ginseng, rhubarb, cascara sagrada, licorice, and senna interacting with corticosteriods; 3) kava, St. John's wort, chamomile, and valerian interacting with central nervous system (CNS) depressant drugs; and 4) herbs acting on the gastrointestinal system, altering the absorption of several orally administered drugs. Further, the use of some herbal supplements has been reported to be associated with oral manifestations, including aphthous ulcers, lip and tongue irritation, and swelling with feverfew; gingival bleeding with feverfew and ginkgo; tongue numbness with echinacea; xerostomia with St. John's wort; oral and lingual dyskinesia with kava; and salivation with yohimbe. These potential effects of herbal supplements in conjunction with factors related to regulation restrictions suggest that the use of these products may be associated with various adverse reactions that can affect oral health and

  12. Antidiabetic treatment with gliptins: focus on cardiovascular effects and outcomes.

    Science.gov (United States)

    Fisman, Enrique Z; Tenenbaum, Alexander

    2015-01-01

    The traditional oral pharmacological therapy for type 2 diabetes mellitus (T2DM) has been based on the prescription of metformin, a biguanide, as first line antihyperglycemic agent world over. It has been demonstrated that after 3 years of treatment, approximately 50% of diabetic patients could achieve acceptable glucose levels with monotherapy; but by 9 years this had declined to only 25%. Therefore, the implementation of a combined pharmacological therapy acting via different pathways becomes necessary, and its combination with a compound of the sulfonylurea group was along decades the most frequently employed prescription in routine clinical practice. Meglitinides, glitazones and alpha-glucosidase inhibitors were subsequently developed, but the five mentioned groups of oral antihyperglycemic agents are associated with variable degrees of undesirable or even severe cardiovascular events. The gliptins-also called dipeptidyl peptidase 4 (DPP4) inhibitors--are an additional group of antidiabetic compounds with increasing clinical use. We review the status of the gliptins with emphasis on their capabilities to positively or negatively affect the cardiovascular system, and their potential involvement in major adverse cardiovascular events (MACE). Alogliptin, anagliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin and vildagliptin are the compounds currently in clinical use. Regardless differences in chemical structure and metabolic pathways, gliptins as a group exert favorable changes in experimental models. These changes, as an almost general rule, include improved endothelial function, reduction of inflammatory markers, oxidative stress ischemia/reperfusion injury and atherogenesis. In addition, increased adiponectin levels and modest decreases in lipidemia and blood pressure were reported. In clinical settings, several trials--notably the longer one, employing sitagliptin, with a mean follow-up period of 3 years--did not show an increased risk for ischemic

  13. Drug-polymer filled micro-containers for oral delivery loaded using supercritical CO2 aided-impregnation

    DEFF Research Database (Denmark)

    Marizza, Paolo; Keller, Stephan Sylvest; Rades, T.

    2013-01-01

    In this work we present an effective loading technique of micro-containers for oral drug delivery of a poorly water soluble drug in a solid dispersion with polymer. By combining inkjet printing and supercritical CO2 impregnation we load ketoprofen in a solid dispersion with poly...

  14. Risk of Non-melanoma Skin Cancer in Patients with Atopic Dermatitis Treated with Oral Immunosuppressive Drugs

    NARCIS (Netherlands)

    Garritsen, Floor M.; Van der Schaft, Jorien; Van den Reek, Juul M.; Politiek, Klaziena; Van Osmedendorp, Harmieke; Van Dijk, Marijke; Hijnen, Dirk J.; De Graaf, Marlies; Bruijnzeel-Koomen, Carla A.; De Jong, Elke M.; Schuttelaar, Marie-Louise A.; De Bruin-Weller, Marjolein S.

    There is uncertainty about the risk of developing non-melanoma skin cancer (NMSC), including basal cell carcinoma and squamous cell carcinoma (SCC), in patients with atopic dermatitis (AD) treated with oral immunosuppressive drugs. A total of 557 patients with AD treated with these drugs in the

  15. [Gynecological use of a phlebokinetic drug with special reference to its combination with oral contraceptives].

    Science.gov (United States)

    Cazzola, D

    1975-09-30

    Controlled experiments confirmed the therapeutic usefulness in gynecology of a phlebokinetic drug, in which EPL (polyunsaturated phosphatidylcholine) was combined with escine and rutine. The drug is particularly recommended for the prophylaxis and treatment of vein disorders caused by oral contraceptives. A total of 75 patients were treated with the drug (Essaven), in addition to the usual treatment (such as anticoagulants), while 75 controls received the usual treatment only. Results were excellent in cases of varicose veins, where the symptoms were eliminated in almost all cases. In cases of phlebitis and thrombophlebitis, the response was less univocal, but a definite improvement was evident in a good number of cases treated with Essaven; the drug also favored the return to normal conditions after thrombophlebitis attacks, reducing the duration of their painful aftereffects. The drug can be used daily for very long periods without side effects. It can also be used safely during pregnancy, without adverse effects on the fetus and on delivery. It is regarded as ideal to avoid the side effects of contraceptives on the venous system.

  16. Functionalized carbon nanomaterials: exploring the interactions with Caco-2 cells for potential oral drug delivery

    Directory of Open Access Journals (Sweden)

    Coyuco JC

    2011-10-01

    Full Text Available Jurja C Coyuco, Yuanjie Liu, Bee-Jen Tan, Gigi NC ChiuDepartment of Pharmacy, Faculty of Science, National University of Singapore, SingaporeAbstract: Although carbon nanomaterials (CNMs have been increasingly studied for their biomedical applications, there is limited research on these novel materials for oral drug delivery. As such, this study aimed to explore the potential of CNMs in oral drug delivery, and the objectives were to evaluate CNM cytotoxicity and their abilities to modulate paracellular transport and the P-glycoprotein (P-gp efflux pump. Three types of functionalized CNMs were studied, including polyhydroxy small-gap fullerenes (OH-fullerenes, carboxylic acid functionalized single-walled carbon nanotubes (fSWCNT-COOH and poly(ethylene glycol functionalized single-walled carbon nanotubes (fSWCNT-PEG, using the well-established Caco-2 cell monolayer to represent the intestinal epithelium. All three CNMs had minimum cytotoxicity on Caco-2 cells, as demonstrated through lactose dehydrogenase release and 3-(4,5-dimethyliazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assays. Of the three CNMs, fSWCNT-COOH significantly reduced transepithelial electrical resistance and enhanced transport of Lucifer Yellow across the Caco-2 monolayer. Confocal fluorescence microscopy showed that fSWCNT-COOH treated cells had the highest perturbation in the distribution of ZO-1, a protein marker of tight junction, suggesting that fSWCNT-COOH could enhance paracellular permeability via disruption of tight junctions. This modulating effect of fSWCNT-COOH can be reversed over time. Furthermore, cellular accumulation of the P-gp substrate, rhodamine-123, was significantly increased in cells treated with fSWCNT-COOH, suggestive of P-gp inhibition. Of note, fSWCNT-PEG could increase rhodamine-123 accumulation without modifying the tight junction. Collectively, these results suggest that the functionalized CNMs could be useful as modulators for oral drug

  17. Emerging integrated nanohybrid drug delivery systems to facilitate the intravenous-to-oral switch in cancer chemotherapy.

    Science.gov (United States)

    Luo, Cong; Sun, Jin; Du, Yuqian; He, Zhonggui

    2014-02-28

    Nanohybrid drug delivery systems have presented lots of characteristic advantages as an efficient strategy to facilitate oral drug delivery. Nonetheless, oral administration of chemotherapy agents by nanoparticulate delivery technology still faces great challenges owing to the multiple biobarriers ranging from poorly physicochemical properties of drugs, to complex gastrointestinal disposition and to presystemic metabolism. This review briefly analyzes a series of biobarriers hindering oral absorption and describes the multiple aspects for facilitating the intravenous-to-oral switch in cancer therapy. Moreover, the developed nanoparticulate drug delivery strategies to overcome the above obstacles are provided, including metabolic enzyme inhibition, enteric-coated nanocarriers, bioadhesive and mucus-penetrating strategies, P-gp inhibition and active targeting. On these foundations, the emerging trends of integrated hybrid nanosystems in response to the present low-efficiency drug delivery of any single approach are summarized, such as mixed polymeric micelles and nanocomposite particulate systems. Finally, the recent advances of high-efficiency hybrid nanoparticles in oral chemotherapy are highlighted, with special attention on integrated approach to design drug delivery nanosystems.

  18. Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers

    Directory of Open Access Journals (Sweden)

    Chih-Hung Lin

    2017-04-01

    Full Text Available Chemical and enzymatic barriers in the gastrointestinal (GI tract hamper the oral delivery of many labile drugs. The GI epithelium also contributes to poor permeability for numerous drugs. Drugs with poor aqueous solubility have difficulty dissolving in the GI tract, resulting in low bioavailability. Nanomedicine provides an opportunity to improve the delivery efficiency of orally administered drugs. Solid lipid nanoparticles (SLNs are categorized as a new generation of lipid nanoparticles consisting of a complete solid lipid matrix. SLNs used for oral administration offer several benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. The nontoxic excipients and sophisticated material engineering of SLNs tailor the controllable physicochemical properties of the nanoparticles for GI penetration via mucosal or lymphatic transport. In this review, we highlight the recent progress in the development of SLNs for disease treatment. Recent application of oral SLNs includes therapies for cancers, central nervous system-related disorders, cardiovascular-related diseases, infection, diabetes, and osteoporosis. In addition to drugs that may be active cargos in SLNs, some natural compounds with pharmacological activity are also suitable for SLN encapsulation to enhance oral bioavailability. In this article, we systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for drug- and natural compound-loaded SLNs.

  19. Drug: D01665 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01665 Drug Voglibose (JP16/USAN/INN); Basen (TN) C10H21NO7 267.1318 267.2762 D01665.gif Antidiabetic...se metabolism hsa04973(8972) Carbohydrate digestion and absorption map07051 Antidiabetics Therapeutic catego...ry of drugs in Japan [BR:br08301] 3 Agents affecting metabolism 39 Other agents affecting metabolism 396 Antidiabetic

  20. Drug: D00216 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available n hsa04973(279+280+8972) Carbohydrate digestion and absorption map07051 Antidiabetics Therapeutic category o...0BF01 Acarbose D00216 Acarbose (JAN/USAN/INN) USP drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic...ting metabolism 396 Antidiabetic agents 3969 Others D00216 Acarbose (JAN/USAN/INN) Anatomical Therapeutic Ch...f drugs in Japan [BR:br08301] 3 Agents affecting metabolism 39 Other agents affec

  1. Ocimum basilicum extract exhibits antidiabetic effects via inhibition of hepatic glucose mobilization and carbohydrate metabolizing enzymes

    Science.gov (United States)

    Ezeani, Chinelo; Ezenyi, Ifeoma; Okoye, Theophine; Okoli, Charles

    2017-01-01

    Aim: Ocimum basilicum L (Lamiaceae) is used as a traditional remedy for different ailments, including diabetes mellitus. This study investigated the antidiabetic effects of an extract of aerial parts of O. basilicum. Methods: Antihyperglycemic effect of the extract was determined by its effects on α-amylase and α-glucosidase in vitro, while antidiabetic properties were studied in alloxan induced diabetic rats treated for 28 days with extract and compared to those treated with oral metformin (150 mg/kg). The study and analysis was conducted between 2014 and 2015. Results: The treatment with 100 and 200 mg/kg extract significantly (P glycogenolysis and/or stimulate glycogenesis. PMID:28163956

  2. Scientific and Regulatory Considerations in Solid Oral Modified Release Drug Product Development.

    Science.gov (United States)

    Li, Min; Sander, Sanna; Duan, John; Rosencrance, Susan; Miksinski, Sarah Pope; Yu, Lawrence; Seo, Paul; Rege, Bhagwant

    2016-11-01

    This review presents scientific and regulatory considerations for the development of solid oral modified release (MR) drug products. It includes a rationale for patient-focused development based on Quality-by-Design (QbD) principles. Product and process understanding of MR products includes identification and risk-based evaluation of critical material attributes (CMAs), critical process parameters (CPPs), and their impact on critical quality attributes (CQAs) that affect the clinical performance. The use of various biopharmaceutics tools that link the CQAs to a predictable and reproducible clinical performance for patient benefit is emphasized. Product and process understanding lead to a more comprehensive control strategy that can maintain product quality through the shelf life and the lifecycle of the drug product. The overall goal is to develop MR products that consistently meet the clinical objectives while mitigating the risks to patients by reducing the probability and increasing the detectability of CQA failures.

  3. Antiepileptic drugs: are women aware of interactions with oral contraceptives and potential teratogenicity?

    Science.gov (United States)

    Pack, Alison M; Davis, Anne R; Kritzer, Jordana; Yoon, Ava; Camus, Adela

    2009-04-01

    Women with epilepsy (WWE)'s knowledge of the interaction between antiepileptic drugs (AEDs) and oral contraceptives (OCs) and the potential teratogenicity of AEDs has received limited study. We conducted a cross-sectional questionnaire study (English or Spanish) among young WWE (18-44 years) to assess demographic characteristics, current AED use, and knowledge of AED interactions with OCs and teratogenicity. We used the Food and Drug Administration's classification system to categorize each AED's teratogenic potential. Participants (n=148) had a mean age of 32 years (SD 8); 32% spoke Spanish and described themselves as Hispanic. Among women prescribed a cytochrome p450-inducing AED, 65% were unaware of decreased OC efficacy. Forty percent of those prescribed Category D AEDs were unaware of potential teratogenic effects. WWE have limited knowledge of the potential interaction between AEDs and OCs and the teratogenic effects of AEDs. Educational efforts should highlight the reproductive health effects of AEDs in WWE.

  4. Oral suspensions of morphine hydrochloride for controlled release: rheological properties and drug release.

    Science.gov (United States)

    Morales, M E; López, G; Gallardo, V; Ruiz, M A

    2011-04-04

    Recent developments in pharmaceutical technology have facilitated the design and production of modified release formulas for drugs whose physical, chemical or biological properties impede release and thus might compromise their efficacy or safety. One such drug is morphine, whose short half-life requires repeated doses at short intervals. The use of biocompatible polymers such as ethylcellulose has made it possible to develop microencapsulated formulations which facilitate liquid, sustained-release pharmaceutical formulas for oral administration. We developed a stable final formulation of morphine with an acceptable release profile by comparing the rheological properties and stability of formulations with different thickeners (xanthan gum, Carbopol, and carboxymethylcellulose with microcrystalline cellulose) at different concentrations from 0.25% to 1.0%. Release assays in a Franz-type cell were done to determine the most suitable release profile for the formulation.

  5. Meta-analysis of Vildagliptin Combined with Other Antidiabetic Drugs in the Treatment of Type 2 Diabetes%维格列汀联合其他降糖药治疗2型糖尿病的疗效与安全性的Meta分析

    Institute of Scientific and Technical Information of China (English)

    缪东军; 邓丽萍

    2016-01-01

    Objective:To discuss Meta analysis of type 2 diabetes mellitus by Vildagliptin combined with other antidiabetic drug.Method:Through the retrieval of the Wanfang,Hownet,VIP and CBM database,type 2 diabetes mellitus,Vildagliptin,combination,hypoglycemic drugs,efficacy,safety were used as the keywords, Meta analysis into the literature were utilized,summarized the efficacy and safety of Vildagliptin combined with other antidiabetic drugs for the treatment of type 2 diabetes.Result:The literature through the screening of this study were included in the final 9 by Meta analysis showed that vildagliptin combination therapy was superior in terms of reducing glycated hemoglobin α-glucosidase inhibitors(P0.05).Conclusion:Meta analysis showed that Vildagliptin in combination with other antidiabetic drugs to treat type 2 diabetes is not only effective and reliable,but also high security,it is worth of learning and using for reference.%目的:探讨2型糖尿病采取维格列汀联合其他降糖药治疗的疗效与安全性的Meta分析情况。方法:通过对万方、知网、维普、CBM等数据库进行检索,将2型糖尿病、维格列汀、联合、降糖药物、疗效、安全性等作为关键词,利用Meta分析纳入的文献,总结维格列汀联合其他降糖药物治疗2型糖尿病的疗效与安全性。结果:通过筛选后最终纳入本研究的文献研究有9个,经Meta分析显示维格列汀联合治疗在降低糖化血红蛋白方面优于α糖苷酶抑制剂(P0.05)。结论:经Meta分析显示维格列汀联合其他降糖药物治疗2型糖尿病不仅疗效可靠,且安全性高,值得借鉴。

  6. 社区医院2008~2010年口服降糖药物应用分析%Analysis of oral hypoglycemic drug use in community hospitals: 2008 ~ 2010

    Institute of Scientific and Technical Information of China (English)

    赵大贵; 杜伟

    2011-01-01

    目的 分析社区医院口服降糖药的应用特点和发展趋势,为临床合理用药提供参考.方法对宜宾市南岸文化广场社区卫生服务中心2008~2010年口服降糖药应用品种、销售金额、用药频度(DDDs)和日均费用(DDC)进行回顾性分析.结果 3年口服降糖药销售金额占抗糖尿病药总金额80%以上;销售金额、DDDs排序前3位的依次是:双胍类、磺酰脲类、餐时血糖调节剂;3年中,二甲双胍缓释片、格列吡嗪缓释片、瑞格列奈位列单品种销售金额前3位;噻唑烷二酮类DDC最高,二甲双胍缓释片、格列吡嗪缓释片DDC较低,在使用上占主导地位.结论社区口服降糖药用药较合理,双胍类、磺酰脲类、餐时血糖调节剂的应用,与社区医院药物治疗糖尿病策略是相符的.%Objective To analyze retrospectively the status quo and tendency of oral hypoglycemic drug use in community hospitals,and provide basis for rational drug use. Methods The article analyzed statistically oral hypoglycemic drugs used during the period of 2008 ~ 2010 in respect of varieties, sales amount,drug daily dosages (DDDS) and defined daily consumption ( DDC). Results The sales amount of oral hypoglycemic drug accounted for more than 80% of the total sales amount of antidiabetic for three successive years. The top three oral hypoglycemic drugs according to sales amount and DDDS were Biguanide,sulfonylurea and prandial glucose regulator. The top three oral hypoglycemic drugs according to sale of single-species were Biguanide,Glipizide Sustained-Release Tablets and Repaglinide. The DDC of thiazolidinediones was the highest,and those of Glipizide Sustained-Release Tablets and Repaglinide were lower,which became the most frequently used drugs in clinic. Conclusion The study shows that the utilization of oral hypoglycemic a-gents in community hospitals is basically rational. Biguanide, sulfonylurea and prandial glucose regulator are used in the way

  7. Improving the prediction of the brain disposition for orally administered drugs using BDDCS

    DEFF Research Database (Denmark)

    Broccatelli, Fabio; Larregieu, Caroline A.; Cruciani, Gabriele;

    2012-01-01

    In modeling blood–brain barrier (BBB) passage, in silico models have yielded ~80% prediction accuracy, and are currently used in early drug discovery. Being derived from molecular structural information only, these models do not take into account the biological factors responsible for the in vivo...... were found to markedly distribute throughout the brain; this includes a number of BDDCS class 1 drugs shown to be Pgp substrates. This new perspective provides a further interpretation of how Pgp influences the sedative effects of H1-histamine receptor antagonists.......In modeling blood–brain barrier (BBB) passage, in silico models have yielded ~80% prediction accuracy, and are currently used in early drug discovery. Being derived from molecular structural information only, these models do not take into account the biological factors responsible for the in vivo...... outcome. Passive permeability and P-glycoprotein (Pgp, ABCB1) efflux have been successfully recognized to impact xenobiotic extrusion from the brain, as Pgp is known to play a role in limiting the BBB penetration of oral drugs in humans. However, these two properties alone fail to explain the BBB...

  8. Development of mannosylated liposomes for bioadhesive oral drug delivery via M cells of Peyer's patches.

    Science.gov (United States)

    Pukanud, Pongthep; Peungvicha, Penchom; Sarisuta, Narong

    2009-07-01

    The aim of this study was to develop mannosylated liposomes as bioadhesive carriers for oral drug delivery. Two kinds of acyclovir (ACV)-entrapped mannosylated liposomes, i.e. ManN-ACV-lip and PAM-ACV-lip, were prepared by the use of mannosamine HCl (ManN) and p-aminophenyl-alpha-D-mannopyranoside (PAM), respectively. The mean sizes, drug entrapment efficiency, and loading capacity values of all liposomal formulations were in the ranges of 233-371 nm, 82-95%, and 42-47%, respectively. The mean size of PAM-ACV-lip was significantly smaller than those of conventional ACV liposomes and ManN-ACV-lip due to the more conical packing parameter of mannose-conjugated phospholipid. The mannosylating group grafted into bilayer membrane resulted in a decrease in drug entrapment, owing to competitive binding. The in vitro drug absorptions through everted sacs of mice ileum of both mannosylated ACV liposomes were significantly higher than those of conventional ACV liposomes or suspension.

  9. Antidiabetic effect of Chloroxylon swietenia bark extracts on streptozotocin induced diabetic rats

    Directory of Open Access Journals (Sweden)

    B. Jayaprasad

    2016-03-01

    Full Text Available Diabetes has been increasing at an alarming rate around the world, and experts have relied on remedies from the utilization of ancient drugs that are essentially derived from plants. The present study aimed to evaluate the antidiabetic potential of Chloroxylon swietenia bark extracts on streptozotocin induced diabetic rats. Diabetes was induced in male albino Wistar rats by single intraperitoneal injection of streptozotocin (STZ (50 mg/kg b.w.. The diabetic rats were administered orally with C. swietenia bark (CSB methanolic (CSBMEt and aqueous (CSBAEt (250 mg/kg b.w. extracts and glibenclamide (600 µg/kg b.w. by intragastric intubation for 45 days. The result showed a heavy loss in weight, increase in blood glucose and glycosylated hemoglobin level, and decline in plasma insulin and total hemoglobin content. Furthermore, glucose-6-phosphatase and fructose-1,6-bis phosphatase were found to be increased whereas hexokinase and glycogen contents were decreased in STZ induced diabetic rats. CSBAEt, CSBMEt and glibenclamide treated diabetic rats showed moderate reduction in blood glucose and glycosylated hemoglobin levels; in addition, plasma insulin and hemoglobin levels were elevated. The altered activities of carbohydrate metabolizing enzymes and liver glycogen were improved remarkably. CSBMEt results were comparable to the standard drug glibenclamide. The present findings support the usage of the plant extracts for the traditional treatment of diabetes.

  10. Antidiabetic thiazolidinediones induce ductal differentiation but not apoptosis in pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    Elisabetta Ceni; Tommaso Mello; Mirko Tarocchi; David W Crabb; Anna Caldini; Pietro Invernizzi; Calogero Surrenti; Stefano Milani; Andrea Galli

    2005-01-01

    AIM: Thiazolidinediones (TZD) are a new class of oral antidiabetic drugs that have been shown to inhibit growth of same epithelial cancer cells. Although TZD were found to be ligands for peroxisome proliferator-activated receptor γ (PPARγ), the mechanism by which TZD exert their anticancer effect is presently unclear. In this study,we analyzed the mechanism by which TZD inhibit growth of human pancreatic carcinoma cell lines in order to evaluate the potential therapeutic use of these drugs in pancreatic adenocarcinoma.METHODS: The effects of TZD in pancreatic cancer cells were assessed in anchorage-independent growth assay.Expression of PPARγ was measured by reverse-transcription polymerase chain reaction and confirmed by Western blot analysis. PPARγ activity was evaluated by transient reporter gene assay. Flow cytometry and DNA fragmentationassay were used to determine the effect of TZD on cell cycle progression and apoptosis respectively. The effect of TZD on ductal differentiation markers was performed by Western blot.RESULTS: Exposure to TZD inhibited colony formation in a PPARγ-dependent manner. Growth inhibition was linked to G1 phase cell cycle arrest through induction of the ductal differentiation program without any increase of the apoptotic rate.CONCLUSION: TZD treatment in pancreatic cancer cells has potent inhibitory effects on growth by a PPAR-dependent induction of pacreatic ductal differentiation.

  11. Anti-diabetic properties of Momordica charantia L. polysaccharide in alloxan-induced diabetic mice.

    Science.gov (United States)

    Xu, Xin; Shan, Bin; Liao, Cai-Hu; Xie, Jian-Hua; Wen, Ping-Wei; Shi, Jia-Yi

    2015-11-01

    A water-soluble polysaccharide (MCP) was isolated from the fruits of Momordica charantia L., and the hypoglycemic effects of MCP were investigated in both normal healthy and alloxan-induced diabetic mice. MCP was orally administered once a day after 3 days of alloxan-induction at 100, 200 and 300mg/kg body weight for 28 day. Results showed that fasting blood glucose level (BGL) was significantly decreased, whereas the glucose tolerance was marked improvement in alloxan-induced diabetic mice, and loss in body weight was also prevented in diabetic mice compared to the diabetic control group. The dosage of 300mg/kg body weight exhibited the best effects. In addition, MCP did not exhibit any toxic symptoms in the limited toxicity evaluation in mice. The results suggest that MCP possess significantly dose-dependent anti-diabetic activity on alloxan-induced diabetic mice. Hence, MCP can be incorporated as a supplement in health-care food, drugs and/or combined with other hypoglycemic drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Antidiabetic Activity of Benzopyrone Analogues in Nicotinamide-Streptozotocin Induced Type 2 Diabetes in Rats

    Directory of Open Access Journals (Sweden)

    Yogendra Nayak

    2014-01-01

    Full Text Available Benzopyrones are proven antidiabetic drug candidate in diabetic drug discovery. In this view novel synthetic benzopyrone analogues were selected for testing in experimental diabetes. Type 2 diabetes (T2D was induced in Wistar rats by streptozotocin (60 mg/kg, i.p. followed by nicotinamide (120 mg/kg i.p.. Rats having fasting blood glucose (FBG >200 mg/dL, 7 days after T2D-induction, are selected for the study. Test compounds and standard treatment were continued for 15 days. FBG, oral glucose tolerance test (OGTT, and insulin tolerance test (ITT were determined on 21st day after induction of T2D. Plasma lipids and serum insulin were estimated. Homeostatic model assessment (HOMA-IR was then calculated from serum insulin. Rats were sacrificed and pancreas was isolated for histopathological observations. Oxidative stress markers were estimated in liver homogenate. Quercetin, a natural product with benzopyrone ring, showed significant hypoglycemic activity comparable to glibenclamide. Treatment with test compounds lowered the FBG and insulin resistance was significant alleviated as determined by OGTT, HOMA-IR, and ITT. There was significant normalisation of liver antioxidant enzymes compared to diabetic rats indicating that all the synthesised benzopyrone analogues are beneficial in reducing oxidative stress and are on par with the standard quercetin and glibenclamide in experimental T2D.

  13. Performance evaluation of on-site oral fluid drug screening devices in normal police procedure in Germany.

    Science.gov (United States)

    Musshoff, Frank; Hokamp, Eva Große; Bott, Ulrich; Madea, Burkhard

    2014-05-01

    There is a need for quick and reliable methods for rapid screening of drug-influenced drivers on the roadside by police. Because the window of detection in oral fluid is more similar to blood than to urine, this matrix should therefore be appropriate for screening procedures. The performance of the Rapid STAT(®) (Mavand Solution GmbH, Mössingen, Germany), DrugWipe5/5+(®) (Securetec Detektions-Systeme AG, Brunnthal, Germany) and Dräger DrugTest(®) 5000 (Draeger Safety AG & Co. KGaA, Luebeck, Germany) on-site oral fluid devices was evaluated with random oral fluid specimens from car drivers in North Rhine-Westphalia (Germany). Additionally, some drivers were checked using an on-site urine device (DrugScreen(®), NAL von Minden, Regensburg, Germany). During a 11-month period, 1.212 drivers were tested. Both OF and urine on-site tests were compared to serum results. The following sensitivities were obtained by the oral fluid devices: THC 71% (DrugWipe(®)), 87% (Dräger), 91% (RapidSTAT); opiates 95% (Dräger), 100% (DrugWipe(®), RapidSTAT(®)); amphetamine 84% (DrugTest(®) 5000), 90% (RapidSTAT(®)), 100% (DrugTest(®) 5000); methamphetamine 50% (DrugTest(®) 5000), 100% (RapidSTAT(®)); cocaine 76% (DrugTest(®) 5000), 100% (DrugWipe(®), RapidSTAT(®)); methadone 33-63%, and benzodiazepines 0-33% (both with a low number of positives). THC specificity was especially low (29% [DrugWipe(®)] and 47% [DrugTest(®) 5000]) due to low cut-off concentrations. These data were similar to those obtained from the literature (e.g., DRUID project). The urine screening device showed a good sensitivity (THC 93%, opiate 94%, amphetamine 94%, methamphetamine 75% (low number of positives), cocaine 100%) and also an acceptable specificity (39%, 86%, 63%, 77%, 47%, respectively). Although oral fluid may be a useful matrix for on-site testing of drugged drivers, it is evident that oral fluid devices still show a lack of sensitivity (methamphetamine, benzodiazepines) and

  14. The challenges and future of oral drug delivery: An interview with David Brayden.

    Science.gov (United States)

    Brayden, David J

    2016-12-01

    David Brayden speaks to Hannah Makin, Commissioning Editor: David Brayden is a Full Professor (Advanced Drug Delivery) at the School of Veterinary Medicine, University College Dublin (UCD) and also a Fellow of the UCD Conway Institute. Following a PhD in Pharmacology at the University of Cambridge, UK (1989), and a postdoctoral research fellowship at Stanford University, CA, USA, he set up Elan Biotechnology Research's in vitro pharmacology laboratory in Dublin (1991). At Elan, he became a senior scientist and project manager of several of Elan's joint-venture drug delivery research collaborations with US biotech companies. In 2001, he joined UCD as a lecturer in veterinary pharmacology and was appointed Associate Professor in 2006 and Full Professor in 2014. He was a Director of the Science Foundation Ireland Research Cluster (The Irish Drug Delivery Research Network) from 2007 to 2013, is a Deputy Coordinator of an FP7 Consortium on oral peptides in nanoparticles ('TRANS-INT', 2012-2017), and is a Co-Principal Investigator in 'CURAM', Science Foundation Ireland's new Centre for Medical Devices (2014-2020 [ 1 ]). He was made a Fellow of the Controlled Release Society in 2012. He is the author or co-author of >200 research publications and patents. D Brayden serves on the Editorial Advisory Boards of Drug Discovery Today, European Journal of Pharmaceutical Sciences, Advanced Drug Delivery Reviews and the Journal of Veterinary Pharmacology and Therapeutics, and is an Associate Editor of Therapeutic Delivery. D Brayden works as an independent consultant for drug delivery companies.

  15. Second generation lipid nanoparticles (NLC) as an oral drug carrier for delivery of lercanidipine hydrochloride.

    Science.gov (United States)

    Ranpise, Nisharani S; Korabu, Swati S; Ghodake, Vinod N

    2014-04-01

    Lercanidipine hydrochloride is a calcium channel blocker used in the treatment of hypertension. It is a poor water soluble drug with absolute bioavailability of 10%. The aim of this study was to design lercanidipine hydrochloride-loaded nanostructured lipid carriers to investigate whether the bioavailability of the same can be improved by oral delivery. Lercanidipine hydrochloride nanostructured lipid carriers were prepared by the method of solvent evaporation at a high temperature and solidification by freeze drying. The nanostructured lipid carriers were evaluated for particle size analysis, zeta potential, entrapment efficiency, in vitro drug diffusion, ex vivo permeation studies and pharmacodynamic study. The resultant nanostructured lipid carriers had a mean size of 214.97 nm and a zeta potential of -31.6 ± 1.5 mV. More than 70% lercanidipine hydrochloride was entrapped in the NLCs. The SEM studies indicated the formation of type 2 nanostructured lipid carriers. The in vitro release studies demonstrated 19.36% release in acidic buffer pH 1.2 indicating that the drug entrapped in the nanostructured lipid carriers remains entrapped at acidic pH. The ex vivo studies indicated that the drug release was enhanced from 10% to 60.54% at blood pH in 24h. The in vivo pharmacodynamic study showed that NLCs released lercanidipine hydrochloride in a controlled manner for a prolonged period of time as compared to plain drug. These results clearly indicate that nanostructured lipid carriers are a potential controlled release formulation for lercanidipine hydrochloride and may be a promising drug delivery system for the treatment of hypertension. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. A REVIEW ON SELF MICRO EMULSIFYING DRUG DELIVERY SYSTEM: AN APPROACH TO ENHANCE THE ORAL BIOAVAILABILITY OF POORLY WATER SOLUBLE DRUGS

    Directory of Open Access Journals (Sweden)

    Shukla Prachi

    2012-09-01

    Full Text Available Technology Catalysts International reported in 2002 that approximately 35-40% of all new chemical compounds suffer from poor aqueous solubility and present a major challenge to modern drug delivery system, because of their low oral bioavailability. Several strategies to improve the solubility and dissolution of poorly water soluble drugs have been developed, which were at start primarily based on modifying the drug’s physicochemical properties. Realization that the oral bioavailability of poor water soluble drugs may be enhanced when co-administered with meal rich in fat has led to increasing recent interest in the formulation of poorly water soluble drugs in lipids. Lipid-based drug delivery systems have gained considerable interest after the commercial success of Sandimmune NeoralTM (Cyclosporine A, Novartis Pvt. Ltd. and Fortovase (Saquinavir, Roche Laboratories Inc. Self micro-emulsifying drug delivery systems are a class of lipid based drug delivery systems. Self micro emulsifying drug delivery systems are isotropic mixtures of oil, surfactant, and co-surfactant and are a vital tool in solving low bioavailability issues of poorly soluble drugs. Lipophilic drugs can be dissolved in these systems, enabling them to be administered as a unit dosage form for per-oral administration. When such a system is released in the lumen of the gastrointestinal tract, it disperses to form a fine w/o microemulsion with the aid of GI fluid. This leads to in situ solubilization of drug that can subsequently be absorbed by lymphatic pathways, bypassing the hepatic first-pass effect. This article represents a complete review on self micro-emulsifying drug delivery system.

  17. Acceptability of rapid oral fluid HIV testing among male injection drug users in Taiwan, 1997 and 2007.

    Science.gov (United States)

    Lyu, Shu-Yu; Morisky, Donald E; Yeh, Ching-Ying; Twu, Shiing-Jer; Peng, Eugene Yu-Chang; Malow, Robert M

    2011-04-01

    Rapid oral fluid HIV testing (rapid oral testing) is in the process of being adapted in Taiwan and elsewhere given its advantages over prior HIV testing methods. To guide this process, we examined the acceptability of rapid oral testing at two time points (i.e., 1997 and 2007) among one of the highest risk populations, male injection drug users (IDUs). For this purpose, an anonymous self-administered survey was completed by HIV-negative IDUs involved in the criminal justice system in 1997 (N (1)=137 parolees) and 2007 (N (2)=106 prisoners). A social marketing model helped guide the design of our questionnaire to assess the acceptability of rapid oral testing. This included assessing a new product, across four marketing dimensions: product, price, promotion, and place. Results revealed that in both 1997 and 2007, over 90% indicated that rapid oral testing would be highly acceptable, particularly if the cost was under US$6, and that a pharmacy would be the most appropriate and accessible venue for selling the rapid oral testing kits. The vast majority of survey respondents believed that the cost of rapid oral testing should be federally subsidized and that television and newspaper advertisements would be the most effective media to advertise for rapid oral testing. Both the 1997 and 2007 surveys suggested that rapid oral HIV testing would be particularly accepted in Taiwan by IDUs after release from the criminal justice system.

  18. Oral fluoroquinolone therapy results in drug adsorption on ureteral stents and prevention of biofilm formation.

    Science.gov (United States)

    Reid, G; Habash, M; Vachon, D; Denstedt, J; Riddell, J; Beheshti, M

    2001-04-01

    The oral administration of ciprofloxacin (250mg bid) and ofloxacin (300mg bid) in 40 patients with ureteral stents, led to drug levels on all the device surfaces that were higher than the minimum inhibitory concentration (MIC) of Escherichia coli (0.004--0.015 mg/l), the most common uropathogen. The drug levels in the film were higher than the MIC of other common pathogens, namely Pseudomonas aeruginosa (0.25--1.0 mg/l), Enterococcus faecalis (0.25--2.0 mg/l) and Staphylococcus aureus (0.12--0.5 mg/l) in a few cases (six, three and 14 cases out of 40, respectively). For both antibiotics, the concentrations were greater than the MIC of many uropathogens on the film surrounding the devices (0.89 vs 0.31 mg/l respectively, P=0.05), and on the devices themselves (0.22 vs. 0.12 mg/l, P=0.207). Adsorption of the antibiotics was higher to the film than to the stent (PCiprofloxacin concentration on the film surrounding the stents was significantly higher than that of ofloxacin (P=0.05), while there was no statistical concentration difference between the two antibiotics adsorbed onto the actual devices (P=0.207). No bacteria were found in patients' urine and no biofilms were detected. This is the first report of an oral antibiotic being adsorbed onto medical devices. It potentially provides a new approach of preventing infection, and avoids the need to pre-coat devices with agents whose use will be restricted once bacteria develop resistance to them. If biomaterial properties can be enhanced to increase further the adsorptive concentration of drug, the risk of infections and recalcitrant biofilm formation could be significantly reduced in a highly susceptible patient population.

  19. 21 CFR 310.534 - Drug products containing active ingredients offered over-the-counter (OTC) for human use as oral...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Drug products containing active ingredients offered over-the-counter (OTC) for human use as oral wound healing agents. 310.534 Section 310.534 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR...

  20. Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation

    Directory of Open Access Journals (Sweden)

    Zhang XW

    2014-11-01

    Full Text Available Xingwang Zhang,* Guijiang Chen,* Tianpeng Zhang, Zhiguo Ma, Baojian WuDivision of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China*These authors contributed equally to this workAbstract: Lipid nanocarriers are becoming a versatile platform for oral delivery of lipophilic drugs. In this article, we aimed to explore the gastrointestinal behaviors of lipid nanoparticles and the effect of PEGylation on oral absorption of fenofibrate (FN, a Biopharmaceutics Classification System (BCS II model drug. FN-loaded PEGylated lipid nanoparticles (FN-PLNs were prepared by the solvent-diffusion method and characterized by particle size distribution, morphology, Fourier transform infrared spectroscopy, and drug release. Lipolytic experiments were performed to assess the resistance of lipid nanoparticles against pancreatic lipase. Pharmacokinetics was evaluated in rats after oral administration of FN preparations. The obtained FN-PLNs were 186.7 nm in size with an entrapment efficiency of >95%. Compared to conventional lipid nanoparticles, PLNs exhibited slower drug release in the lipase-containing medium, strikingly reduced mucin binding, and suppressed lipolysis in vitro. Further, oral absorption of FN was significantly enhanced using PLNs with relative bioavailability of 123.9% and 157.0% to conventional lipid nanoparticles and a commercial formulation (Lipanthyl®, respectively. It was demonstrated that reduced mucin trapping, suppressed lipolysis, and/or improved mucosal permeability were responsible for increased oral absorption. These results facilitated a better understanding of the in vivo fate of lipid nanoparticles, and suggested the potential of PLNs as oral carriers of BCS II drugs.Keywords: fenofibrate, lipid nanoparticles, PEGylation, oral bioavailability, absorption mechanism

  1. An alternative approach to determine oral bioavailability of drugs that follow Michaelis-Menten elimination: a case study with voriconazole.

    Science.gov (United States)

    Verlindo de Araujo, Bibiana; Farias da Silva, Cristófer; Costa, Teresa Dalla

    2010-01-01

    the determination of oral bioavailability of drugs which follow nonlinear pharmacokinetics is difficult and few methods are available. In this work, an alternative approach to determine oral bioavailability of voriconazole (VRC), used as a model drug, is presented. VRC pharmacokinetics was investigated in Wistar rats after p.o. (40 mg/kg) and i.v. administration (2.5, 5 and 10 mg/kg). VRC elimination showed saturation in all doses investigated, except the lower i.v. dose in which case a 3-compartment model with linear elimination adequately fitted the data. Data for the 2 higher i.v. doses were best described by a 3-compartment model with Michaelis-Menten elimination. A 1-compartment disposition with a saturable metabolic elimination model described the oral profile. VRC absolute oral bioavailability was determined by simultaneous fitting of the i.v. and oral profiles. the Michaelis constant and the maximum velocity estimated after 5 and 10 mg/kg i.v. dosing were 0.54 +/- 0.25 microg/ml and 2.53 +/- 0.54 microg/h, and 0.62 +/- 0.12 microg/ml and 2.74 +/- 0.84 microg/h, respectively. VRC oral bioavailability was determined to be 82.8%. the approach presented is an alternative for determining the bioavailability of drugs with similar nonlinear behavior. 2010 S. Karger AG, Basel.

  2. Demonstrating Bioequivalence of Locally Acting Orally Inhaled Drug Products (OIPs): Workshop Summary Report.

    Science.gov (United States)

    Adams, Wallace P; Ahrens, Richard C; Chen, Mei-Ling; Christopher, David; Chowdhury, Badrul A; Conner, Dale P; Dalby, Richard; Fitzgerald, Kevin; Hendeles, Leslie; Hickey, Anthony J; Hochhaus, Günther; Laube, Beth L; Lucas, Paul; Lee, Sau L; Lyapustina, Svetlana; Li, Bing; O'Connor, Dennis; Parikh, Neil; Parkins, David A; Peri, Prasad; Pitcairn, Gary R; Riebe, Michael; Roy, Partha; Shah, Tushar; Singh, Gur Jai Pal; Sharp, Sandra Suarez; Suman, Julie D; Weda, Marjolein; Woodcock, Janet; Yu, Lawrence

    2010-02-01

    This March 2009 Workshop Summary Report was sponsored by Product Quality Research Institute (PQRI) based on a proposal by the Inhalation and Nasal Technology Focus Group (INTFG) of the American Association of Pharmaceutical Scientists (AAPS). Participants from the pharmaceutical industry, academia and regulatory bodies from the United States, Europe, India, and Brazil attended the workshop with the objective of presenting, reviewing, and discussing recommendations for demonstrating bioequivalence (BE) that may be considered in the development of orally inhaled drug products and regulatory guidances for new drug applications (NDAs), abbreviated NDAs (ANDAs), and postapproval changes. The workshop addressed areas related to in vitro approaches to demonstrating BE, biomarker strategies, imaging techniques, in vivo approaches to establishing local delivery equivalence and device design similarity. The workshop presented material that provided a baseline for the current understanding of orally inhaled drug products (OIPs) and identified gaps in knowledge and consensus that, if answered, might allow the design of a robust, streamlined method for the BE assessment of locally acting inhalation drugs. These included the following: (1) cascade impactor (CI) studies are not a good 2 predictor of the pulmonary dose; more detailed studies on in vitro/in vivo correlations (e.g., suitability of CI studies for assessing differences in the regional deposition) are needed; (2) there is a lack of consensus on the appropriate statistical methods for assessing in vitro results; (3) fully validated and standardized imaging methods, while capable of providing information on pulmonary dose and regional deposition, might not be applicable to the BE of inhaled products mainly due to the problems of having access to radiolabeled innovator product; (4) if alternatives to current methods for establishing local delivery BE of OIPs cannot be established, biomarkers (pharmacodynamic or clinical

  3. Drug: D00335 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00335 Drug Glipizide (USP/INN); Glucotrol (TN) C21H27N5O4S 445.1784 445.5352 D00335.gif Antidiabetic...USP/INN) USP drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic Agents Glipizide D00335

  4. Drug: D08491 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08491 Drug Rosiglitazone (INN); Gaudil (TN) C18H19N3O3S 357.1147 357.4268 D08491.gif Antidiabetic...1 Rosiglitazone (INN) USP drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic

  5. Immobilization of coacervate microcapsules in multilayer sodium alginate beads for efficient oral anticancer drug delivery.

    Science.gov (United States)

    Feng, Chao; Song, Ruixi; Sun, Guohui; Kong, Ming; Bao, Zixian; Li, Yang; Cheng, Xiaojie; Cha, Dongsu; Park, Hyunjin; Chen, Xiguang

    2014-03-10

    We have designed and evaluated coacervate microcapsules-immobilized multilayer sodium alginate beads (CMs-M-ALG-Beads) for oral drug delivery. The CMs-M-ALG-Beads were prepared by immobilization of doxorubicin hydrochloride (DOX) loaded chitosan/carboxymethyl coacervate microcapsules (DOX:CS/CMCS-CMs) in the core and layers of the multilayer sodium alginate beads. The obtained CMs-M-ALG-beads exhibited layer-by-layer structure and rough surface with many nanoscale particles. The swelling characteristic and drug release results indicated that 4-layer CMs-M-ALG-Beads possessed favorable gastric acid tolerance (the swelling rate <5%, the cumulative drug release rate <3.8%). In small intestine, the intact DOX:CS/CMCS-CMs were able to rapidly release from CMs-M-ALG-Beads with the dissolution of ALG matrix. Ex vivo intestinal mucoadhesive and permeation showed that CMs-M-ALG-Beads exhibited continued growth for P(app) values of DOX, which was 1.07-1.15 folds and 1.28-1.38 folds higher than DOX:CS:CMCS-CMs in rat jejunum and ileum, respectively, demonstrating that CMs-M-ALG-Beads were able to enhance the absorption of DOX by controlled releasing DOX:CS/CMCS-CMs and prolonging the contact time between the DOX:CS/CMCS-CMs and small intestinal mucosa.

  6. Drug: D00944 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 81 165.6246 D00944.gif Antidiabetic [DS:H00409] Therapeutic category: 3962 ATC code: A10BA02 biguanides AMPK... SCL47A2 [HSA:146802] map07051 Antidiabetics map04150 mTOR signaling pathway Therapeutic category of drugs i...n Japan [BR:br08301] 3 Agents affecting metabolism 39 Other agents affecting metabolism 396 Antidiabetic...min D00944 Metformin hydrochloride (JP16/USP) USP drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic

  7. Imipramine is an orally active drug against both antimony sensitive and resistant Leishmania donovani clinical isolates in experimental infection.

    Directory of Open Access Journals (Sweden)

    Sandip Mukherjee

    Full Text Available BACKGROUND: In an endeavor to find an orally active and affordable antileishmanial drug, we tested the efficacy of a cationic amphiphilic drug, imipramine, commonly used for the treatment of depression in humans. The only available orally active antileishmanial drug is miltefosine with long half life and teratogenic potential limits patient compliance. Thus there is a genuine need for an orally active antileishmanial drug. Previously it was shown that imipramine, a tricyclic antidepressant alters the protonmotive force in promastigotes, but its in vivo efficacy was not reported. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that the drug is highly active against antimony sensitive and resistant Leishmania donovani in both promastigotes and intracellular amastigotes and in LD infected hamster model. The drug was found to decrease the mitochondrial transmembrane potential of Leishmania donovani (LD promastigotes and purified amastigotes after 8 h of treatment, whereas miltefosine effected only a marginal change even after 24 h. The drug restores defective antigen presenting ability of the parasitized macrophages. The status of the host protective factors TNF α, IFN γ and iNOS activity increased with the concomitant decrease in IL 10 and TGF β level in imipramine treated infected hamsters and evolution of matured sterile hepatic granuloma. The 10-day therapeutic window as a monotherapy, showing about 90% clearance of organ parasites in infected hamsters regardless of their SSG sensitivity. CONCLUSIONS: This study showed that imipramine possibly qualifies for a new use of an old drug and can be used as an effective orally active drug for the treatment of Kala-azar.

  8. Anti-diabetic effect of a combination of andrographolide-enriched extract of Andrographis paniculata (Burm f.) Nees and asiaticoside-enriched extract of Centella asiatica L. in high fructose-fat fed rats.

    Science.gov (United States)

    Nugroho, Agung Endro; Lindawati, Novena Yety; Herlyanti, Kyky; Widyastuti, Lina; Pramono, Suwidjiyo

    2013-12-01

    Traditionally, a combination of medicinal plants is commonly used for lowering blood glucose in diabetic patients in order to provide additional benefits of the single drug. A. paniculata and C. asiatica are two traditional medicines form South Asian and Southeast Asain countries consumed by people for treating daibates mellitus and its complications. Hyperglycemia in the rats was stimulated by high fructose-fat diet that consists of 36% fructose, 15% lard, and 5% egg yolks in 0.36 g/200 g body weight for 70 days. The rats were orally administered with the combination of andrographolide-enriched extract of A. paniculata (AEEAP) leaves and asiaticoside-enriched extract of C. asiatica (AEECA) herbs from day 70 for 7 days. Antidiabetic activity was evaluated by estimating mainly the blood glucose levels and other parameters such as HDL, LDL, cholesterol and triglyceride. The results showed that combination at the ratio of 70:30 exhibited a promosing antidiabetic effect in high-fat-fructose-fed rat, and exhibited sinergistic effects on blood cholesterol and HDL levels. It can be concluded that its antidiabetic effect was better than that of single treatment of AEEAP or AEECA. That combination was also potential to develop as a blood glucose-lowering agent for diabetic patients.

  9. Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists

    Science.gov (United States)

    Seow, Vernon; Lim, Junxian; Cotterell, Adam J.; Yau, Mei-Kwan; Xu, Weijun; Lohman, Rink-Jan; Kok, W. Mei; Stoermer, Martin J.; Sweet, Matthew J.; Reid, Robert C.; Suen, Jacky Y.; Fairlie, David P.

    2016-04-01

    Drug discovery and translation are normally based on optimizing efficacy by increasing receptor affinity, functional potency, drug-likeness (rule-of-five compliance) and oral bioavailability. Here we demonstrate that residence time of a compound on its receptor has an overriding influence on efficacy, exemplified for antagonists of inflammatory protein complement C5a that activates immune cells and promotes disease. Three equipotent antagonists (3D53, W54011, JJ47) of inflammatory responses to C5a (3nM) were compared for drug-likeness, receptor affinity and antagonist potency in human macrophages, and anti-inflammatory efficacy in rats. Only the least drug-like antagonist (3D53) maintained potency in cells against higher C5a concentrations and had a much longer duration of action (t1/2 ~ 20 h) than W54011 or JJ47 (t1/2 ~ 1-3 h) in inhibiting macrophage responses. The unusually long residence time of 3D53 on its receptor was mechanistically probed by molecular dynamics simulations, which revealed long-lasting interactions that trap the antagonist within the receptor. Despite negligible oral bioavailability, 3D53 was much more orally efficacious than W54011 or JJ47 in preventing repeated agonist insults to induce rat paw oedema over 24 h. Thus, residence time on a receptor can trump drug-likeness in determining efficacy, even oral efficacy, of pharmacological agents.

  10. Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs

    Directory of Open Access Journals (Sweden)

    Varaporn Buraphacheep Junyaprasert

    2015-02-01

    Full Text Available Nanocrystals, a carrier-free colloidal delivery system in nano-sized range, is an interesting approach for poorly soluble drugs. Nanocrystals provide special features including enhancement of saturation solubility, dissolution velocity and adhesiveness to surface/cell membranes. Several strategies are applied for nanocrystals production including precipitation, milling, high pressure homogenization and combination methods such as NanoEdge™, SmartCrystal and Precipitation-lyophilization-homogenization (PLH technology. For oral administration, many publications reported useful advantages of nanocrystals to improve in vivo performances i.e. pharmacokinetics, pharmacodynamics, safety and targeted delivery which were discussed in this review. Additionally, transformation of nanocrystals to final formulations and future trends of nanocrystals were also described.

  11. [Pharmacogenetics of oral anticoagulants: individualized drug treatment for more efficacy and safety].

    Science.gov (United States)

    Loriot, Marie-Anne; Beaune, Philippe

    2007-06-30

    Oral anti-vitamin K (AVK) anticoagulants constitute the first cause of iatrogenic accidents in France because of narrow therapeutic index and bleeding risk. The wide interindividual variation in AVK response is partly genetically determined. The main enzyme responsible for the metabolism of AVK is the hepatic cytochrome P450 2C9 (CYP2C9). Vitamine K epoxide reductase complex subunit I (VKORC1) is a key enzyme in the vitamin K cycle, cofactor required for the activation of vitamin K-dependent clotting factors, and is the target enzyme of AVK inhibition. Genetic variations affecting both CYP2C9 and VKORC1 are associated with variability in drug response and may explain differences in dose requirements. Genotyping for CYP2C9 and VKORC1 variants before initiation of treatment may allow clinicians to develop dosing protocols and identify the patients at a higher risk for bleeding complications.

  12. Stabilisation of amorphous furosemide increases the oral drug bioavailability in rats

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Rades, Thomas; Müllertz, Anette

    2015-01-01

    solution after oral dosing to rats. The glass solution had a glass transition temperature of 121.3 +/- 0.5 degrees C, which was significantly higher than that of the pure drug (101.2 degrees C). ASSF in the glass solution was stable for at least 168 days when stored at 20 degrees C and 0% relative humidity....... The glass solution exhibited fast dissolution in simulated intestinal medium, pH 6.5; the intrinsic dissolution rate was found to be 10.1 +/- 0.6 mg/cm(2)/min, which was significantly faster than the pure ASSF. When investigating the stability during dissolution in stimulated intestinal medium at pH 6...

  13. Deciding oral drugs after metformin in type 2 diabetes: An evidence-based approach

    Directory of Open Access Journals (Sweden)

    Awadhesh Kumar Singh

    2014-01-01

    Full Text Available The most commonly used oral drug in treating type 2 diabetes (T2DM after metformin are sufonylureas (SUs based on the confidence gained over the several decades and because of its cheaper cost. Unfortunately, SUs are associated with secondary failure and sometimes associated with therapy related severe hypoglycaemia limiting its compliance and wider utility in current clinical practice. Although large randomised trials could not associate SUs with any obvious increase in cardiovascular (CV mortality, some recent larger databases showing divergent results suggesting increasingly CV signals and this might put SUs in difficulty given the availability of other safer alternatives. In recent years, incretin-based therapies like dipeptidyl peptidase-4 inhibitors (DPP-4I and glucagon-like peptide-1 (GLP-1 agonist (GLP-1A are gaining popularity primarily because of their advantage of weight reduction/neutrality and minimal hypoglycemia along with the perception of possible pleiotropic CV benefit mainly derived from pooled CV data of their trials. Sodium glucose transporter 2 inhibitors (SGLT-2I are another new promising molecule currently looking for its space in the management of T2DM. Insulin could be utilized at any place when required and in this regard outcomes reduction with an initial glargine intervention (ORIGIN study also suggested that basal insulin glargine could be safely used even in early stage. This review will discuss what could be possibly be the best option as a second line oral agent, once metformin monotherapy becomes ineffective.

  14. Lipid nanoparticles with no surfactant improve oral absorption rate of poorly water-soluble drug.

    Science.gov (United States)

    Funakoshi, Yuka; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

    2013-07-15

    A pharmacokinetic study was performed in rats to evaluate the oral absorption ratios of nanoparticle suspensions containing the poorly water-soluble compound nifedipine (NI) and two different types of lipids, including hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol. NI-lipid nanoparticle (LN) suspensions with a mean particle size of 48.0 nm and a zeta potential of -57.2 mV were prepared by co-grinding combined with a high-pressure homogenization process. The oral administration of NI-LN suspensions to rats led to a significant increase in the NI plasma concentration, and the area under the curve (AUC) value was found to be 108 min μg mL⁻¹, indicating a 4-fold increase relative to the NI suspensions. A comparison of the pharmacokinetic parameters of the NI-LN suspensions with those of the NI solution prepared using only the surfactant polysorbate 80 revealed that although the AUC and bioavailability (59%) values were almost identical, a rapid absorption rate was still observed in the NI-LN suspensions. These results therefore indicated that lipid nanoparticles prepared using only two types of phospholipid with a mean particle size of less than 50 nm could improve the absorption of the poorly water-soluble drug. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway.

    Science.gov (United States)

    Li, Chen; Chen, Zhongxiu; Yang, Hao; Luo, Fangbo; Chen, Lihong; Cai, Huawei; Li, Yajiao; You, Guiying; Long, Dan; Li, Shengfu; Zhang, Qiuping; Rao, Li

    2016-01-01

    Although extracellular-regulated kinases (ERK) are a well-known central mediator in cardiac hypertrophy, no clinically available ERK antagonist has been tested for preventing cardiac hypertrophy. Selumetinib is a novel oral MEK inhibitor that is currently under Phase II and Phase III clinical investigation for advanced solid tumors. In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy. In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. This selective ERK inhibition prevented left ventricular (LV) wall thickening, LV mass increase, fetal gene reactivation and cardiac fibrosis. In another distinct physiologic cardiac hypertrophy model of a swimming rat, Selumetinib provided a similar anti-hypertrophy effect, except that no significant fetal gene reactivation or cardiac fibrosis was observed. Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. These promising results indicate that Selumetinib could potentially be used to treat cardiac hypertrophy. However, this hypothesis needs to be validated in human clinical trials.

  16. Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway.

    Directory of Open Access Journals (Sweden)

    Chen Li

    Full Text Available Although extracellular-regulated kinases (ERK are a well-known central mediator in cardiac hypertrophy, no clinically available ERK antagonist has been tested for preventing cardiac hypertrophy. Selumetinib is a novel oral MEK inhibitor that is currently under Phase II and Phase III clinical investigation for advanced solid tumors. In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy.In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. This selective ERK inhibition prevented left ventricular (LV wall thickening, LV mass increase, fetal gene reactivation and cardiac fibrosis. In another distinct physiologic cardiac hypertrophy model of a swimming rat, Selumetinib provided a similar anti-hypertrophy effect, except that no significant fetal gene reactivation or cardiac fibrosis was observed.Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. These promising results indicate that Selumetinib could potentially be used to treat cardiac hypertrophy. However, this hypothesis needs to be validated in human clinical trials.

  17. Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway

    Science.gov (United States)

    Yang, Hao; Luo, Fangbo; Chen, Lihong; Cai, Huawei; Li, Yajiao; You, Guiying; Long, Dan; Li, Shengfu; Zhang, Qiuping; Rao, Li

    2016-01-01

    Aims Although extracellular-regulated kinases (ERK) are a well-known central mediator in cardiac hypertrophy, no clinically available ERK antagonist has been tested for preventing cardiac hypertrophy. Selumetinib is a novel oral MEK inhibitor that is currently under Phase II and Phase III clinical investigation for advanced solid tumors. In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy. Methods and Results In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. This selective ERK inhibition prevented left ventricular (LV) wall thickening, LV mass increase, fetal gene reactivation and cardiac fibrosis. In another distinct physiologic cardiac hypertrophy model of a swimming rat, Selumetinib provided a similar anti-hypertrophy effect, except that no significant fetal gene reactivation or cardiac fibrosis was observed. Conclusions Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. These promising results indicate that Selumetinib could potentially be used to treat cardiac hypertrophy. However, this hypothesis needs to be validated in human clinical trials. PMID:27438013

  18. Analysis of Intra- and Intersubject Variability in Oral Drug Absorption in Human Bioequivalence Studies of 113 Generic Products.

    Science.gov (United States)

    Sugihara, Masahisa; Takeuchi, Susumu; Sugita, Masaru; Higaki, Kazutaka; Kataoka, Makoto; Yamashita, Shinji

    2015-12-07

    In this study, the data of 113 human bioequivalence (BE) studies of immediate release (IR) formulations of 74 active pharmaceutical ingredients (APIs) conducted at Sawai Pharmaceutical Co., Ltd., was analyzed to understand the factors affecting intra- and intersubject variabilities in oral drug absorption. The ANOVA CV (%) calculated from area under the time-concentration curve (AUC) in each BE study was used as an index of intrasubject variability (Vintra), and the relative standard deviation (%) in AUC was used as that of intersubject variability (Vinter). Although no significant correlation was observed between Vintra and Vinter of all drugs, Vintra of class 3 drugs was found to increase in association with a decrease in drug permeability (P(eff)). Since the absorption of class 3 drugs was rate-limited by the permeability, it was suggested that, for such drugs, the low P(eff) might be a risk factor to cause a large intrasubject variability. To consider the impact of poor water solubility on the variability in BE study, a parameter of P(eff)/Do (Do; dose number) was defined to discriminate the solubility-limited and dissolution-rate-limited absorption of class 2 drugs. It was found that the class 2 drugs with a solubility-limited absorption (P(eff)/Do < 0.149 × 10(-4) cm/s) showed high intrasubject variability. Furthermore, as a reason for high intra- or intersubject variability in AUC for class 1 drugs, effects of drug metabolizing enzymes were investigated. It was demonstrated that intrasubject variability was high for drugs metabolized by CYP3A4 while intersubject variability was high for drugs metabolized by CYP2D6. For CYP3A4 substrate drugs, the Km value showed the significant relation with Vintra, indicating that the affinity to the enzyme can be a parameter to predict the risk of high intrasubject variability. In conclusion, by analyzing the in house data of human BE study, low permeability, solubility-limited absorption, and high affinity to CYP3A4 are

  19. Antidiabetic activities of aqueous and ethanolic extracts of Piper betle leaves in rats.

    Science.gov (United States)

    Arambewela, L S R; Arawwawala, L D A M; Ratnasooriya, W D

    2005-11-14

    Leaves of Piper betle (Piperaceae) possess several bioactivities and are used in traditional medicinal systems. However, its antidiabetic activity has not been scientifically investigated so far. The aim of this study therefore, was to investigate the antidiabetic activity of Piper betle leaves. This was tested in normoglycaemic and strepozotocin (STZ)-induced diabetic rats using oral administration of hot water extract (HWE) and cold ethanolic extract (CEE). In normoglycaemic rats, both HWE and CEE significantly lowered the blood glucose level in a dose-dependent manner. In glucose tolerance test, both extracts markedly reduced the external glucose load. The antidiabetic activity of HWE is comparable to that of CEE. Moreover, HWE failed to inhibit the glucose absorption from the small intestine of rats. Both extracts were found to be non-toxic and well tolerated after following chronic oral administration (no overt signs of toxicity, hepatotoxicity or renotoxicity). However, the weight of the spleen had increased in treated groups possibly indicating lymphoproliferative activity. It is concluded that HWE and CEE of Piper betle leaves possess safe and strong antidiabetic activity.

  20. Drug-induced QT-interval shortening following antiepileptic treatment with oral rufinamide.

    Science.gov (United States)

    Schimpf, Rainer; Veltmann, Christian; Papavassiliu, Theano; Rudic, Boris; Göksu, Turgay; Kuschyk, Jürgen; Wolpert, Christian; Antzelevitch, Charles; Ebner, Alois; Borggrefe, Martin; Brandt, Christian

    2012-05-01

    The arrhythmogenic potential of short QT intervals has recently been highlighted in patients with a short QT syndrome. Drug-induced QT-interval prolongation is a known risk factor for ventricular tachyarrhythmias. However, reports on drug-induced QT-interval shortening are rare and proarrhythmic effects remain unclear. Recently, rufinamide, a new antiepileptic drug for the add-on treatment of Lennox-Gastaut syndrome, was approved in the European Union and the United States. Initial trials showed drug-induced QT-interval shortening. The aim of our study was to evaluate the effects of rufinamide on QT intervals in patients with difficult-to-treat epilepsies. Nineteen consecutive patients with Lennox-Gastaut syndrome and other epilepsy syndromes were included (n = 12 men; mean age 41 ± 12 years). QRS, QT, and T(peak)-T(end) intervals were analyzed before and during rufinamide treatment. The mean QT interval shortened significantly following rufinamide administration (QT interval 349 ± 23 ms vs 327 ± 17 ms; corrected QT interval 402 ± 22 ms vs 382 ± 16 ms; P = .002). T(peak)-T(end) intervals were 79 ± 17 ms before and 70 ± 20 ms on treatment (P = .07). The mean reduction of the corrected QT interval was 20 ± 18 ms. During follow-up (3.04 ± 1.09 years), no adverse events including symptomatic cardiac arrhythmias or sudden cardiac deaths were observed. QTc-interval shortening following oral rufinamide administration in a small patient group was not associated with significant clinical adverse effects. These observations notwithstanding, the ability of rufinamide to significantly shorten the QT interval portends a potential arrhythmogenic risk that may best be guarded against by periodic electrocardiographic recordings. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  1. Molecular pharmacodynamics of new oral drugs used in the treatment of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    di Nuzzo L

    2014-05-01

    Full Text Available Luigi di Nuzzo,1 Rosamaria Orlando,2 Carla Nasca,1 Ferdinando Nicoletti1,31Department of Physiology and Pharmacology, Sapienza University of Rome, 2IRCCS Associazione Oasi Maria S.S., Institute for Research on Mental Retardation and Brain Aging, Troina, Enna, 3IRCCS Neuromed, Pozzilli, ItalyAbstract: New oral drugs have considerably enriched the therapeutic armamentarium for the treatment of multiple sclerosis. This review focuses on the molecular pharmacodynamics of fingolimod, dimethyl fumarate (BG-12, laquinimod, and teriflunomide. We specifically comment on the action of these drugs at three levels: 1 the regulation of the immune system; 2 the permeability of the blood–brain barrier; and 3 the central nervous system. Fingolimod phosphate (the active metabolite of fingolimod has a unique mechanism of action and represents the first ligand of G-protein-coupled receptors (sphingosine-1-phosphate receptors active in the treatment of multiple sclerosis. Dimethyl fumarate activates the nuclear factor (erythroid-derived 2-related factor 2 pathway of cell defense as a result of an initial depletion of reduced glutathione. We discuss how this mechanism lies on the border between cell protection and toxicity. Laquinimod has multiple (but less defined mechanisms of action, which make the drug slightly more effective on disability progression than on annualized relapse rate in clinical studies. Teriflunomide acts as a specific inhibitor of the de novo pyrimidine biosynthesis. We also discuss new unexpected mechanisms of these drugs, such as the induction of brain-derived neurotrophic factor by fingolimod and the possibility that laquinimod and teriflunomide regulate the kynurenine pathway of tryptophan metabolism.Keywords: demyelinating diseases, pharmacotherapy, fingolimod, dimethyl fumarate, laquinimod, teriflunomide

  2. [Impact of slow-release oral morphine on drug abusing habits in Austria].

    Science.gov (United States)

    Beer, Beate; Rabl, Walter; Libiseller, Kathrin; Giacomuzzi, Salvatore; Riemer, Yvonne; Pavlic, Marion

    2010-01-01

    A well-established possibility to treat opiate addiction is the participation in opiate maintenance treatment programmes. For this purpose the opioids methadone and buprenorphine have been evaluated and are used nowadays in many countries. However, since 1998 also the use of slow-release oral morphine (SROM) has been legally permitted in Austria. Our data show that these morphine preparations are frequently abused and are dominating the black market in the meantime. Especially the intravenous consumption of SROM goes along with highly dangerous side effects that exceed the risks of needle sharing alone. Special galenics are supposed to ensure a 24 h effect of the otherwise quickly metabolised morphine. If dissolved and injected, insoluble contents such as talcum cause microembolisms, leading to severe damages of the inner organs. Furthermore, SROM, i.e. a drug prescribed by physicians, has been proved to be the main responsible substance in most drug related deaths since its permission and has nearly replaced heroin. Forensic physicians play a major role in the profound examination of these cases, including extensive toxicological analyses and interpretation of results. For instance, a differentiation between a recent morphine and heroin consumption is certainly possible, provided appropriate methods are used. A reliable estimation of the current situation of drug abusing habits is a premise for adequate therapeutic offers and preventive measures. Thus, well-founded and comparable data have to be collected. To facilitate data report a standardized report form has been developed that includes an obligatory statement regarding morphine or heroin consumption. This should help to enlighten the ongoing discussion on the role of SRM in drug abuse cases. Our results indicate that the prescription of SROM in opiate maintenance therapy has to be handled very strictly and should be reserved for special patients only. A slackening of the Austrian law concerning SROM is

  3. MARKETING STUDIES OF LOCAL MARKET OF DRUGS WHICH ARE APPLIED FOR PREVENTION AND TREATMENT OF ORAL CAVITY DISEASES

    Directory of Open Access Journals (Sweden)

    O. A. Tsarakhov

    2015-01-01

    Full Text Available Stomatological market has actively developed recent years. Domestic experts received an access to contemporary technologies of dental diseases treatment in the world. This conditioned the appearance of new drugs and parapharmaceutical products applied in dental practice on the pharmaceutical market. In this connection, study of these drugs market, their price policy, demand and supply. Assortment of parapharmaceutical products applied in dental practice for oral cavity hygiene is represented mainly by liquid forms, such as mouth rinse, balms, elixirs, and a special place is occupied by toothpastes. Their assortment amounts to more than 700 types. Drugs, applied in dental practice are represented by the following groups: anti-inflammatory, antimicrobial, antiallergenic, anesthetics, drugs which stimulate tissues regeneration, fluoric drugs. The purpose of this study was the analysis of regional pharmaceutical market assortment, which offers parapharmaceutical goods and drugs for prevention and treatment of oral cavity diseases to the stomatological establishments. Pharmaceutical market of the Republic of North Ossetia – Alania is represented by a wide range of drugs for dental diseases treatment. This group is represented in the assortment of practically all distributors. The drugs for dental diseases treatment is not only supplied by domestic producers but also go from pharmaceutical companies of 29 foreign countries, which influences positively on the state of drug therapy of paradontum in the region.

  4. Association Between Loyalty to Community Pharmacy and Medication Persistence and Compliance, and the Use of Guidelines-Recommended Drugs in Type 2 Diabetes: A Cohort Study.

    Science.gov (United States)

    Dossa, Anara Richi; Grégoire, Jean-Pierre; Lauzier, Sophie; Guénette, Line; Sirois, Caroline; Moisan, Jocelyne

    2015-07-01

    Pharmacists record data on all drugs claimed and may build a personal relationship with their clients. We hypothesized that loyalty to a single pharmacy could be associated with a better quality of drug use.To assess the association between pharmacy loyalty and quality of drug use among individuals treated with oral antidiabetes drugs (OADs).This is a cohort study using Quebec Health Insurance Board data. Associations were assessed using multivariable logistic regression.New OAD users, aged ≥18 years.Individuals who filled all their prescription drugs in the same pharmacy during the first year of treatment were considered loyal. During year 2 of treatment we assessed 4 quality indicators of drug use: persistence with antidiabetes treatment, compliance with antidiabetes treatment among those considered persistent, use of an angiotensin-converting enzyme inhibitor or of an angiotensin II receptor blocker (ACEi/ARB), and use of a lipid-lowering drug.Of 124,009 individuals, 59.75% were identified as loyal. Nonloyal individuals were less likely to persist with their antidiabetes treatment (adjusted odds ratio = 0.89; 95% CI: 0.86-0.91), to comply with their antidiabetes treatment (0.82; 0.79-0.84), to use an ACEi/ARB (0.85; 0.83-0.88) and to use a lipid-lowering drug (0.83; 0.80-0.85). Quality of drug use decreased as the number of different pharmacies increased (linear contrast tests loyalty are specifically due to pharmacists.

  5. Association Between Loyalty to Community Pharmacy and Medication Persistence and Compliance, and the Use of Guidelines-Recommended Drugs in Type 2 Diabetes

    Science.gov (United States)

    Dossa, Anara Richi; Grégoire, Jean-Pierre; Lauzier, Sophie; Guénette, Line; Sirois, Caroline; Moisan, Jocelyne

    2015-01-01

    Abstract Pharmacists record data on all drugs claimed and may build a personal relationship with their clients. We hypothesized that loyalty to a single pharmacy could be associated with a better quality of drug use. To assess the association between pharmacy loyalty and quality of drug use among individuals treated with oral antidiabetes drugs (OADs). This is a cohort study using Quebec Health Insurance Board data. Associations were assessed using multivariable logistic regression. New OAD users, aged ≥18 years. Individuals who filled all their prescription drugs in the same pharmacy during the first year of treatment were considered loyal. During year 2 of treatment we assessed 4 quality indicators of drug use: persistence with antidiabetes treatment, compliance with antidiabetes treatment among those considered persistent, use of an angiotensin-converting enzyme inhibitor or of an angiotensin II receptor blocker (ACEi/ARB), and use of a lipid-lowering drug. Of 124,009 individuals, 59.75% were identified as loyal. Nonloyal individuals were less likely to persist with their antidiabetes treatment (adjusted odds ratio = 0.89; 95% CI: 0.86–0.91), to comply with their antidiabetes treatment (0.82; 0.79–0.84), to use an ACEi/ARB (0.85; 0.83–0.88) and to use a lipid-lowering drug (0.83; 0.80–0.85). Quality of drug use decreased as the number of different pharmacies increased (linear contrast tests loyalty are specifically due to pharmacists. PMID:26166087

  6. Taste Masked Orally Disintegrating Pellets of Antihistaminic and Mucolytic Drug: Formulation, Characterization, and In Vivo Studies in Human

    OpenAIRE

    Taj, Yasmeen; Pai, Roopa S.; V. Kusum Devi; Singh, Gurinder

    2014-01-01

    The main aim of the present study was to evaluate the potential of orally disintegrating pellets (ODPs) as an approach for taste masking of bitter drugs, namely, Ambroxol hydrochloride (A-HCl) and Cetirizine dihydrochloride (C-DHCl). Pellets were prepared by extrusion/spheronization with Eudragit EPO, kyron T-134, Kyron T-314, mannitol, sorbitol, MCC (Avicel PH-101), sucralose, chocolate flavor, and 5% xanthum gum. The prepared pellets were characterized for percentage yield, drug content, pa...

  7. Taste Masked Orally Disintegrating Pellets of Antihistaminic and Mucolytic Drug: Formulation, Characterization, and In Vivo Studies in Human

    OpenAIRE

    Taj, Yasmeen; Pai,Roopa S.; V Kusum Devi; Singh,Gurinder

    2014-01-01

    The main aim of the present study was to evaluate the potential of orally disintegrating pellets (ODPs) as an approach for taste masking of bitter drugs, namely, Ambroxol hydrochloride (A-HCl) and Cetirizine dihydrochloride (C-DHCl). Pellets were prepared by extrusion/spheronization with Eudragit EPO, kyron T-134, Kyron T-314, mannitol, sorbitol, MCC (Avicel PH-101), sucralose, chocolate flavor, and 5% xanthum gum. The prepared pellets were characterized for percentage yield, drug content, pa...

  8. International Guidelines for Bioequivalence of Systemically Available Orally Administered Generic Drug Products: A Survey of Similarities and Differences

    OpenAIRE

    Davit, Barbara; Braddy, April C.; Conner, Dale P.; Yu, Lawrence X.

    2013-01-01

    The objective of this article is to discuss the similarities and differences among bioequivalence approaches used by international regulatory authorities when reviewing applications for marketing new generic drug products which are systemically active and intended for oral administration. We focused on the 13 jurisdictions and organizations participating in the International Generic Drug Regulators Pilot. These are Australia, Brazil, Canada, China, Chinese Taipei, the European Medicines Assoc...

  9. Thiazolidinediones are associated with a decreased risk of atrial fibrillation compared with other antidiabetic treatment

    DEFF Research Database (Denmark)

    Pallisgaard, Jannik Langtved; Lindhardt, Tommi Bo; Staerk, Laila;

    2017-01-01

    AIM: The aim of this study was to investigate the association between thiazolidinediones (TZDs) vs. other antidiabetic drugs and risk of atrial fibrillation (AF) in diabetic patients. METHOD AND RESULTS: Diabetes mellitus (diabetes) increases the risk of AF by approximately 34%. TZD is an insulin...

  10. Bioavailability Enhancement of Paclitaxel via a Novel Oral Drug Delivery System: Paclitaxel-Loaded Glycyrrhizic Acid Micelles

    Directory of Open Access Journals (Sweden)

    Fu-Heng Yang

    2015-03-01

    Full Text Available Paclitaxel (PTX, taxol, a classical antitumor drug against a wide range of tumors, shows poor oral bioavailability. In order to improve the oral bioavailability of PTX, glycyrrhizic acid (GA was used as the carrier in this study. This was the first report on the preparation, characterization and the pharmacokinetic study in rats of PTX-loaded GA micelles The PTX-loaded micelles, prepared with ultrasonic dispersion method, displayed small particle sizes and spherical shapes. Differential scanning calorimeter (DSC thermograms indicated that PTX was entrapped in the GA micelles and existed as an amorphous state. The encapsulation efficiency was about 90%, and the drug loading rate could reach up to 7.90%. PTX-loaded GA micelles displayed a delayed drug release compared to Taxol in the in vitro release experiment. In pharmacokinetic study via oral administration, the area under the plasma concentration-time curve (AUC0→24 h of PTX-loaded GA micelles was about six times higher than that of Taxol (p < 0.05. The significant oral absorption enhancement of PTX from PTX-loaded GA micelles could be largely due to the increased absorption in jejunum and colon intestine. All these results suggested that GA would be a promising carrier for the oral delivery of PTX.

  11. A Study on the Reliability of an On-Site Oral Fluid Drug Test in a Recreational Context

    Directory of Open Access Journals (Sweden)

    Stefano Gentili

    2016-01-01

    Full Text Available The reliability of DrugWipe 5A on site test for principal drugs of abuse (cannabis, amphetamines, cocaine, and opiates detection in oral fluid was assessed by comparing the on-site results with headspace solid-phase microextraction (HS-SPME gas chromatography-mass spectrometry (GC-MS analysis on samples extracted by the device collection pad. Oral fluid samples were collected at recreational settings (e.g., discos, pubs, and music bars of Rome metropolitan area. Eighty-three club goers underwent the on-site drug screening test with one device. Independently from the result obtained, a second device was used just to collect another oral fluid sample subsequently extracted and analyzed in the laboratory following HS-SPME procedure, gas chromatographic separation by a capillary column, and MS detection by electron impact ionization. DrugWipe 5A on-site test showed 54 samples (65.1% positive to one or more drugs of abuse, whereas 75 samples (90.4% tested positive for one or more substances following GC-MS assay. Comparing the obtained results, the device showed sensitivity, specificity, and accuracy around 80% for amphetamines class. Sensitivity (67 and 50% was obtained for cocaine and opiates, while both sensitivity and accuracy were unsuccessful (29 and 53%, resp. for cannabis, underlying the limitation of the device for this latter drug class.

  12. Stereospermum tetragonam as an antidiabetic agent by activating PPARγ and GLUT4

    Directory of Open Access Journals (Sweden)

    Bino Kingsley

    2014-06-01

    Full Text Available Present study evaluates the anti-diabetic activity of S. tetragonam LC-MSMS experiments showed the presence of two novel molecules C1 and C2, which were further taken for in silico study against PPARγ. Cell culture studies with A431 cells in the presence of crude aqueous extract showed the elevated level of PPARγ and GLUT4 and also confirmed using in silico studies. Thus, the present study proves the mecode of action of S. tetragonam as an antidiabetic drug.

  13. Drug: D08378 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08378 Drug Pioglitazone (INN); Actos (TN) C19H20N2O3S 356.1195 356.4387 D08378.gif Antidiabetic...:br08302] Blood Glucose Regulators Antidiabetic Agents Pioglitazone D08378 pioglitazone (INN) Target-based c...1577 1551] map07051 Antidiabetics map07222 Peroxisome proliferator-activated rece...) gamma agonist [HSA:5468] [KO:K08530] hsa03320(5468) PPAR signaling pathway CYP induction: CYP3A [HSA:1576

  14. Drug: D04121 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ys Asn Gly Gly Pro Ser Ser Gly Ala Pro Pro Pro Ser Peptide Antidiabetic [DS:H00409] Same as: C15894 Therapeu... Neuroactive ligand-receptor interaction hsa04911(2740) Insulin secretion map07051 Antidiabetics Therapeutic...nsulins A10BX04 Exenatide D04121 Exenatide (JAN/USAN/INN) USP drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic

  15. Drug: D01854 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available st (TN) (C19H24NO3)2. 2H2O. Ca 704.335 704.9061 D01854.gif Antidiabetic [DS:H00409] Therapeutic category: 39... Type II diabetes mellitus Enzyme: UGT1A9 [HSA:54600], UGT1A3 [HSA:54659] map07051 Antidiabetics Therapeutic... category of drugs in Japan [BR:br08301] 3 Agents affecting metabolism 39 Other agents affecting metabolism 396 Antidiabetic

  16. Drug Survival and reasons for discontinuation of intramuscular methotrexate: a study of 212 consecutive patients switching from oral methotrexate

    DEFF Research Database (Denmark)

    Linde, Louise; Hetland, Merete Lund; Østergaard, Mikkel

    2006-01-01

    Drug survival and reasons for discontinuation of intramuscular methotrexate: a study of 212 consecutive patients switching from oral methotrexate.Linde L, Hetland ML, Ostergaard M. Department of Rheumatology, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Denmark. louiselinde......@dadlnet.dk OBJECTIVES: To assess the drug survival and reasons for discontinuation of intramuscular methotrexate (imMTX) in rheumatological patients who had switched to imMTX from oral methotrexate (oMTX). METHODS: Data from 212 consecutive patients who switched from oMTX to imMTX therapy at our outpatient clinic...... had stopped oMTX because of adverse events, 22% also withdrew from imMTX because of adverse events. CONCLUSION: Half of the patients benefited from switching from oral to intramuscular methotrexate for at least 6 months, but only a minority adhered to the treatment for years. Lack of efficacy...

  17. Formulation and evaluation of gastroretentive microballoons containing baclofen for a floating oral controlled drug delivery system.

    Science.gov (United States)

    Dube, T S; Ranpise, N S; Ranade, A N

    2014-01-01

    The objective of the present study was to fabricate and evaluate a multiparticulate oral gastroretentive dosage form of baclofen characterized by a central large cavity (hollow core) promoting unmitigated floatation with practical applications to alleviate the signs and symptoms of spasticity and muscular rigidity. Solvent diffusion and evaporation procedure were applied to prepare floating microspheres with a central large cavity using various combinations of ethylcellulose (release retardant) and HPMC K4M (release modifier) dissolved in a mixture of dichloromethane and methanol (2:1). The obtained microspheres (700-1000 µm) exhibit excellent floating ability (86 ± 2.00%) and release characteristics with entrapment efficiency of 95.2 ± 0.32%. Microspheres fabricated with ethylcellulose to HPMC K4M in the ratio 8.5:1.5 released 98.67% of the entrapped drug in 12 h. Muscle relaxation caused by baclofen microspheres impairs the rotarod performance for more than 12 h. Abdominal X-ray images showed that the gastroretention period of the floating barium sulfate- labeled microspheres was no less than 10 h. The buoyant baclofen microspheres provide a promising gastroretentive drug delivery system to deliver baclofen in spastic patients with a sustained release rate.

  18. Evaluation of ten oral fluid point-of-collection drug-testing devices.

    Science.gov (United States)

    Walsh, J Michael; Crouch, Dennis J; Danaceau, Jonathan P; Cangianelli, Leo; Liddicoat, Laura; Adkins, Randy

    2007-01-01

    Previously, the laboratory evaluations of six point-of-collection oral fluid (POC-OF) drug testing devices were reported. Four additional devices, Oralstat (American Bio Medica); SmartClip (Envitec); Impact (LifePoint); and OraLine IV s.a.t (Sun Biomedical Laboratories), were recently evaluated for their ability to meet the claimed (and proposed) cutoff concentrations set by the manufacturers for the detection of amphetamine(s), cocaine/metabolite, opiates, and cannabinoids (Oralstat also benzodiazepines). With the exception of the Sun Biomedical device, actual false-positive results were not encountered. Most devices performed well for the detection of opiates and amphetamine(s), but approximately half had amphetamine(s) cutoff concentrations greater than that proposed by the Substance Abuse and Mental Health Services Administration (SAMHSA). Only three devices had cocaine cutoffs less than or equal to 20 ng/mL (SAMHSA), and a number of false-negative results were obtained. The devices still were not capable of detecting Delta(9)-tetrahydrocannabinol at 4 ng/mL (SAMHSA). However, sensitivities improved since the initial studies, and approximately half of the devices met the THC-COOH cutoff proposed by SAMHSA. Results from the current and previous evaluations are presented in the paper and indicate that the sensitivity and performance of commercial OF drug testing devices is improving, but remains problematic for the reliable detection of cannabinoid use.

  19. Successful lung transplantation for talcosis secondary to intravenous abuse of oral drug

    Directory of Open Access Journals (Sweden)

    Dekel Shlomi

    2008-06-01

    Full Text Available Dekel Shlomi1, David Shitrit1, Daniele Bendayan1, Gidon Sahar2, Yitshak Shechtman3, Mordechai R Kramer11Pulmonary Institute, Departments of 2Cardiothoracic Surgery and 3Pathology, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelAbstract: Talcosis due to intravenous injection of oral drugs can cause severe pulmonary disease with progressive dyspnea even when drug use is discontinued. We describe a 54-yearold woman with severe emphysema who underwent left lung transplantation. The patient had a remote history of intravenous injection of crushed methylphenidate (Ritalin tablets. Chest computed tomography showed severe emphysematous changes, more prominent in the lower lobes. Microscopic examination of the extracted lung demonstrated multinucleated giant cells with birefringent crystals, compatible with talcosis. At follow-up, daily symptoms were completely alleviated and lung function was good. We recommend that lung transplantation be considered as a viable option in the treatment of talcosis.Keywords: methylphenidate (Ritalin, emphysema

  20. International Guidelines for Bioequivalence of Locally Acting Orally Inhaled Drug Products: Similarities and Differences.

    Science.gov (United States)

    Lu, Dongmei; Lee, Sau L; Lionberger, Robert A; Choi, Stephanie; Adams, Wallace; Caramenico, Hoainhon N; Chowdhury, Badrul A; Conner, Dale P; Katial, Rohit; Limb, Susan; Peters, John R; Yu, Lawrence; Seymour, Sally; Li, Bing V

    2015-05-01

    International regulatory agencies have developed recommendations and guidances for bioequivalence approaches of orally inhaled drug products (OIDPs) for local action. The objective of this article is to discuss the similarities and differences among these approaches used by international regulatory authorities when applications of generic and/or subsequent entry locally acting OIDPs are evaluated. We focused on four jurisdictions that currently have published related guidances for generic and/or subsequent entry OIDPs. They are Therapeutic Goods Administration (TGA) in Australia, Health Canada (HC) in Canada, European Medicines Association (EMA) of European Union (EU), and the Food and Drug Administration (FDA) in the United States of America (USA). The comparisons of these bioequivalence (BE) recommendations are based on selection of reference products, formulation and inhaler device comparisons, and in vitro tests and in vivo studies, including pharmacokinetic (PK), pharmacodynamics (PD), and clinical studies. For the in vivo studies, the study design, choices of dose, subject inclusion/ exclusion criteria, study period, study endpoint, and equivalence criteria are elaborated in details. The bioequivalence on multiple-strength products and waiver options are also discussed.