Pharmaceutical development of an intravenous dosage form of diacetylmorphine hydrochloride

NARCIS (Netherlands)

Klous, Marjolein G.; Nuijen, Bastiaan; van den Brink, Wim; van Ree, Jan M.; Beijnen, Jos H.

2004-01-01

A solid dosage form for multiple use was developed for parenteral administration of diacetylmorphine in a clinical trial on co-prescription of heroin to heroin addicts. A 300-mg/mL diacetylmorphine hydrochloride solution was lyophilised as 10-mL aliquots in 30-mL glass vials, to be reconstituted to

Quantitative estimation of diacetylmorphine by preparative TLC and UV spectroscopy

International Nuclear Information System (INIS)

Khan, L.; Siddiqui, M.T.; Ahmad, N.; Shafi, N.

2001-01-01

A simple and efficient method for the quantitative estimation of di acetylmorphine in narcotic products has been described. Comparative TLC of narcotic specimens with standards showed presence of morphine, monoacetylmorphine, diacetylmorphine papaverine and noscapine, Resolution of the mixtures was achieved by preparative TLC. Bands corresponding to diacetylmorphine scraped, eluted UV absorption of extracts measured and contents quantified. (author)

Population pharmacokinetics of caffeine and its metabolites theobromine, paraxanthine and theophylline after inhalation in combination with diacetylmorphine

NARCIS (Netherlands)

Zandvliet, Anthe S.; Huitema, Alwin D. R.; de Jonge, Milly E.; den Hoed, Rob; Sparidans, Rolf W.; Hendriks, Vincent M.; van den Brink, Wim; van Ree, Jan M.; Beijnen, Jos H.

2005-01-01

The stimulant effect of caffeine, as an additive in diacetylmorphine preparations for study purposes, may interfere with the pharmacodynamic effects of diacetylmorphine. In order to obtain insight into the pharmacology of caffeine after inhalation in heroin users, the pharmacokinetics of caffeine

Volatilisation of diacetylmorphine: in vitro simulation of 'chasing the dragon'

NARCIS (Netherlands)

Klous, M. G.; Lee, W. C.; van den Brink, W.; van Ree, J. M.; Beijnen, J. H.

2006-01-01

In preparation for a trial on co-prescription of heroin to chronic treatment-resistant addicts, a pharmaceutical dosage form for smokable heroin was developed. During development of this product (a mixture of diacetylmorphine and caffeine), in vitro experiments were performed simulating 'chasing the

Rapid comparison of diacetylmorphine on banknotes by tandem mass spectrometry.

Science.gov (United States)

Ebejer, Karl A; Brereton, Richard G; Carter, James F; Ollerton, Samantha L; Sleeman, Richard

2005-01-01

A procedure is described for the determination of the distribution of the contamination of banknotes with controlled drugs using tandem mass spectrometry. The method is illustrated using diacetylmorphine, which is the major active component of heroin. A series of banknotes is introduced into the mass spectrometer and the intensities of two product ions (m/z 328 and 268) derived from the precursor protonated molecule (m/z 370) are recorded. A banknote is considered contaminated if it shows a significant peak for both product ions, and if the ratio of intensities of these two peaks falls within accepted limits. The distribution of diacetylmorphine on sterling banknotes taken from general circulation within the UK can be modelled by an arcsin (square root) transformation of the data or by a log transformation of the data with a higher proportion of contamination. The two models were found to be in close agreement, predicting an upper limit (at 99.9% confidence) of contamination on banknotes from general circulation between 9 and 10%. The percentage contamination in a case study was calculated and compared to the background distribution using the two models proposed. This comparison revealed that the contamination present in the case study was inconsistent with that present on banknotes in general circulation. (c) 2005 John Wiley & Sons, Ltd.

Analysis of diacetylmorphine, caffeine, and degradation products after volatilization of pharmaceutical heroin for inhalation

NARCIS (Netherlands)

Klous, Marjolein G.; Lee, WeiChing; Hillebrand, Michel J. X.; van den Brink, Wim; van Ree, Jan M.; Beijnen, Jos H.

2006-01-01

Pharmaceutical smokable heroin was developed for a clinical trial on medical co-prescription of heroin and methadone. This product, consisting of 75% w/w diacetylmorphine base and 25% w/w caffeine anhydrate, was intended for use via "chasing the dragon", that is, inhalation after volatilization.

Population pharmacokinetics of caffeine and its metabolites theobromine, paraxanthine and theophylline after inhalation in combination with diacetylmorphine.

Science.gov (United States)

Zandvliet, Anthe S; Huitema, Alwin D R; de Jonge, Milly E; den Hoed, Rob; Sparidans, Rolf W; Hendriks, Vincent M; van den Brink, Wim; van Ree, Jan M; Beijnen, Jos H

2005-01-01

The stimulant effect of caffeine, as an additive in diacetylmorphine preparations for study purposes, may interfere with the pharmacodynamic effects of diacetylmorphine. In order to obtain insight into the pharmacology of caffeine after inhalation in heroin users, the pharmacokinetics of caffeine and its dimethylxanthine metabolites were studied. The objectives were to establish the population pharmacokinetics under these exceptional circumstances and to compare the results to published data regarding intravenous and oral administration in healthy volunteers. Diacetylmorphine preparations containing 100 mg of caffeine were used by 10 persons by inhalation. Plasma concentrations of caffeine, theobromine, paraxanthine and theophylline were measured by high performance liquid chromatography. Non-linear mixed effects modelling was used to estimate population pharmacokinetic parameters. The model was evaluated by the jack-knife procedure. Caffeine was rapidly and effectively absorbed after inhalation. Population pharmacokinetics of caffeine and its dimethylxanthine metabolites could adequately and simultaneously be described by a linear multi-compartment model. The volume of distribution for the central compartment was estimated to be 45.7 l and the apparent elimination rate constant of caffeine at 8 hr after inhalation was 0.150 hr(-1) for a typical individual. The bioavailability was approximately 60%. The presented model adequately describes the population pharmacokinetics of caffeine and its dimethylxanthine metabolites after inhalation of the caffeine sublimate of a 100 mg tablet. Validation proved the stability of the model. Pharmacokinetics of caffeine after inhalation and intravenous administration are to a large extent similar. The bioavailability of inhaled caffeine is approximately 60% in experienced smokers.

Client satisfaction among participants in a randomized trial comparing oral methadone and injectable diacetylmorphine for long-term opioid-dependency

Directory of Open Access Journals (Sweden)

Brissette Suzanne

2011-07-01

Full Text Available Abstract Background Substitution with opioid-agonists (e.g., methadone has shown to be an effective treatment for chronic long-term opioid dependency. Patient satisfaction with treatment has been associated with improved addiction treatment outcomes. However, there is a paucity of studies evaluating patients' satisfaction with Opioid Substitution Treatment (OST. In the present study, participants' satisfaction with OST was evaluated at 3 and 12 months. We sought to test the relationship between satisfaction and patients' characteristics, the treatment modality received and treatment outcomes. Methods Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI, conducted in Vancouver and Montreal (Canada between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone vs. injectable diacetylmorphine over 12 months. A small sub-group of patients received injectable hydromorphone on a double blind basis with diacetylmorphine. The Client Satisfaction Questionnaire (CSQ-8 was used to measure satisfaction with treatment. CSQ-8 scores, as well as retention and response to treatment, did not differ between those receiving hydromorphone and diacetylmorphine at 3 or 12 months assessments; therefore, these two groups were analyzed together as the 'injectable' treatment group. Results A total of 232 (92% and 237 (94% participants completed the CSQ-8 at 3 and 12 months, respectively. Participants in both groups were highly satisfied with treatment. Independent of treatment group, participants satisfied with treatment at 3 months were more likely to be retained at 12 months. Multivariate analysis indicated that satisfaction was greater among those randomized to the injection group after controlling for treatment effectiveness. Participants who were retained, responded to treatment, and had fewer psychological symptoms were more satisfied with treatment. Finally, open-ended comments were made by

Heroin-assisted treatment showed better efficacy than methadone

OpenAIRE

ANSSEAU, Marc; Demaret, Isabelle

2014-01-01

Background: A fraction of patients receiving methadone treatment pursues their use of street heroin. In Switzerland, a new treatment with prescribed diacetylmorphine (pharmaceutical heroin) was developed to help these heroin addicts resistant to methadone treatment to decrease their street heroin use. In this heroin-assisted treatment (HAT), diacetylmorphine is prescribed to severe heroin user and diacetylmorphine is administered by patients under the supervision of nurses in a...

Employment and paid work among participants in a randomized controlled trial comparing diacetylmorphine and hydromorphone.

Science.gov (United States)

Nikoo, Mohammadali; Vogel, Marc; Choi, Fiona; Song, Michael J; Burghardt, Jensen; Zafari, Zafar; Tabi, Katarina; Frank, Anastasia; Barbic, Skye; Schütz, Christian; Jang, Kerry; Krausz, Michael

2018-04-12

Employment is one of the less studied but a significant outcome of medication-assisted treatment. Thus, we aimed to explore employment outcomes of medication-assisted treatment with hydromorphone (HDM) or diacetylmorphine (DAM). The secondary aim was to estimate characteristics of this population as well as treatment-related factors associated with these outcomes. This was a secondary analysis of a randomized, double blind controlled trial. A total of 102 and 100 participants were randomized to receive injectable DAM or HDM for 6 months respectively. In stage 2, 144 participants were randomized again to receive either oral or injectable forms of the medication they received for another 6 months. Participants were interviewed at 5 timepoints: before and 3, 6, 9 and 12 months after treatment assignment. Generalized estimating equations (GEE) with a logit link was fitted to determine factors related to paid work in the past 30 days. Mean age of participants was 44.3 (SD = 9.6) and 59 (29.2%) participants were men. At each timepoint, 6-8 (3.6%-4.1%) participants reported employment in the past 30 days and 40 to 52 (19.7%-26.7%) reported minimum 1 day of paid work. University or college education [OR = 2.12: 95% CI = (1.25, 3.62), P = 0.01] was significantly associated with paid work after adjustment for age, gender, treatment arms, timepoints, days receiving study treatment, physical health, psychological health and crack cocaine use in the past 30 days. The rate of employment was lower among participants of this study compared to similar studies on heroin-assisted treatment. Higher education was associated with increased odds of paid work. A large gap exists between employment rate and the proportion of participants who reported paid work. Supported employment and occupational therapy could optimize the employment outcomes of this population. Copyright © 2018 Elsevier B.V. All rights reserved.

The association between nicotine dependence and physical health among people receiving injectable diacetylmorphine or hydromorphone for the treatment of chronic opioid use disorder

Directory of Open Access Journals (Sweden)

Heather Palis

2018-06-01

Full Text Available Introduction: People with chronic opioid use disorder often present to treatment with individual and structural vulnerabilities and remain at risk of reporting adverse health outcomes. This risk is greatly compounded by tobacco smoking, which is highly prevalent among people with chronic opioid use disorder. Despite the known burden of tobacco smoking on health, the relationship between nicotine dependence and health has not been studied among those receiving injectable opioid agonist treatment. As such, the present study aims to explore the association between nicotine dependence and physical health among participants of the Study to Assess Longer-Term Opioid Medication Effectiveness (SALOME at baseline and six-months. Methods: SALOME was a double-blind phase III clinical trial testing the non-inferiority of injectable hydromorphone to injectable diacetylmorphine for chronic opioid use disorder. Participants reporting tobacco smoking were included in a linear regression analysis of physical health at baseline (before receiving treatment and at six-months. Results: At baseline, nicotine dependence score, lifetime history of emotional, physical, or sexual abuse and prior month safe injection site access were independently and significantly associated with physical health. At six-months nicotine dependence score was the only variable that maintained this significant and independent association with physical health. Conclusions: Findings indicate that after six-months, the injectable treatment effectively brought equity to patients' physical health status, yet the association with nicotine dependence remained. Findings could inform whether the provision of treatment for nicotine dependence should be made a priority in settings where injectable opioid agonist treatment is delivered to achieve improvements in overall physical health in this population.

Five years audit for presence of toxic agents/drug of abuse at autopsy

International Nuclear Information System (INIS)

Ali, S.M.A.; Khalil, I.R.; Saeed, A.; Hussain, Z.

2003-01-01

Objective: To know the frequency of fatal poisoning in Peshawar regarding the toxic agents mostly involved and year wise percentage. To know the age group and the gender that is most vulnerable to fatal poisoning. Results: Poisoning was the cause of death in 1.48% of the total autopsies conducted during the five years. Males were more involved than the females, 90.38%. Suicidal poisoning was present in 17.30% of the total cases and accidental poisoning was found in 80.72% cases, while homicidal cases were 1.29% only. Diacetylmorphine (heroin) was the most commonly involved agent, 65.38%, of the total cases. The incidence of poisoning was more during the third and fourth decades of life. Conclusion: Diacetylmorphine (heroin) was the main causative agent involved in young males due to accidental over-dosage. Accidental and suicidal deaths should not be considered as inevitable. More elaborative studies are required in this area of recent research to adopt appropriate and adequate measures to save precious lives.(author)

Hemodynamic, Thyroid and Immunomodulatory Effects of Heroin in Rats

Directory of Open Access Journals (Sweden)

Ismail M. Maulood

2016-05-01

Full Text Available Diacetylmorphine (heroin has many effects on the body system; it exerts effects on cardiovascular, immune and endocrine systems. The aim of the this study is to investigate the short-term effects of low and high doses of heroin on systolic blood pressure (SBP, thyroid hormones and monocyte chemoattractant protein-1 (MCP-1. The experimental rats were divided into three groups, each with six individuals and the treatments were continued for seven days. SBP significantly reduced by heroin administration in the second dose as compared with the control group. A marked decrease in the serum NO level was also noticed after first (low and second (high dose of administration as compared with control group. The present results also revealed that serum MCP-1 was statistically increased in the second dose of heroin group. Statistical analysis showed that both serum T3 and T4 levels were reduced significantly by heroin administration. In conclusions, for the first time, our findings suggested that diacetylmorphine could affect immune system through MCP-1 elevation. As well as heroin may affect cardiac and liver functions via increasing troponin-T and bilirubin levels.

The distribution of controlled drugs on banknotes via counting machines.

Science.gov (United States)

Carter, James F; Sleeman, Richard; Parry, Joanna

2003-03-27

Bundles of paper, similar to sterling banknotes, were counted in banks in England and Wales. Subsequent analysis showed that the counting process, both by machine and by hand, transferred nanogram amounts of cocaine to the paper. Crystalline material, similar to cocaine hydrochloride, could be observed on the surface of the paper following counting. The geographical distribution of contamination broadly followed Government statistics for cocaine usage within the UK. Diacetylmorphine, Delta(9)-tetrahydrocannabinol (THC) and 3,4-methylenedioxymethylamphetamine (MDMA) were not detected during this study.

Pharmaceutical development of diacetylmorphine preparations for prescription to opioid dependent patients

NARCIS (Netherlands)

Klous, Marjolein Gabriëlle

2004-01-01

Addiction to heroin is a common problem in many countries around the world. Nowadays, addiction has been accepted as a chronic, relapsing psychiatric disorder. Pharmacological treatments have been developed, but stabilisation of drug use and harm reduction have become the focus of therapy for a

Pharmaceutical development of diacetylmorphine preparations for prescription to opioid dependent patients

OpenAIRE

Klous, Marjolein Gabriëlle

2004-01-01

Addiction to heroin is a common problem in many countries around the world. Nowadays, addiction has been accepted as a chronic, relapsing psychiatric disorder. Pharmacological treatments have been developed, but stabilisation of drug use and harm reduction have become the focus of therapy for a subgroup of chronic addicts, for whom treatment options are limited. Presently, there is considerable interest in heroin-assisted treatment (HAT): (co-)prescription of heroin to chronic, treatment-refr...

Cytokines, Chaperones and Neuroinflammatory Responses in Heroin-Related Death: What Can We Learn from Different Patterns of Cellular Expression?

Directory of Open Access Journals (Sweden)

Vittorio Fineschi

2013-09-01

Full Text Available Heroin (3,6-diacetylmorphine has various effects on the central nervous system with several neuropathological alterations including hypoxic-ischemic brain damage from respiratory depressing effects and neuroinflammatory response. Both of these mechanisms induce the release of cytokines, chemokines and other inflammatory mediators by the activation of many cell types such as leucocytes and endothelial and glial cells, especially microglia, the predominant immunocompetent cell type within the central nervous system. The aim of this study is to clarify the correlation between intravenous heroin administration in heroin related death and the neuroinflammatory response. We selected 45 cases among autopsies executed for heroin-related death (358 total cases; immunohistochemical studies and Western blotting analyses were used to investigate the expression of brain markers such as tumor necrosis factor-α, oxygen-regulated protein 150, (interleukins IL-1β, IL-6, IL-8, IL-10, IL-15, cyclooxygenase-2, heat shock protein 70, and CD68 (MAC387. Findings demonstrated that morphine induces inflammatory response and cytokine release. In particular, oxygen-regulated protein 150, cyclooxygenase-2, heat shock protein 70, IL-6 and IL-15 cytokines were over-expressed with different patterns of cellular expression.

Screening for illicit drugs on Euro banknotes by LC-MS/MS.

Science.gov (United States)

Wimmer, Kurt; Schneider, Serge

2011-03-20

A method for the simultaneous quantification of illicit drugs on Euro banknotes, using an ultra-performance liquid chromatography tandem mass spectrometry, was developed and validated. The method included cocaine, benzoylecgonine, MDMA, MDEA, MDA, methamphetamine, diacetylmorphine, 6-MAM, morphine and Δ(9)-THC. Drug residues were monitored and quantified via positive ESI mode using multiple reaction monitoring. Banknotes were extracted with methanol by vigorous shaking. Recovery rates were in the range of 60-80%. Calibration was performed with spiked banknotes in the range of 10-100 ng/note (R(2) 0.98-0.99). Intra-day analysis showed fair precision and accuracy (≤ 15%). Matrix effects were in the range from 27% to 235%. 7-15 samples of each denomination were analyzed. The calculated median values per note were 106 ng cocaine, 43 ng benzoylecgonine, 41 ng heroin, 15.5 ng 6-MAM, 16.5 ng morphine, 9 ng MDMA and 7 ng methamphetamine. Δ(9)-THC was detected on 4 banknotes. MDEA and MDA were not detected on any note. A widespread background contamination for cocaine and opiates was demonstrated. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Dgroup: DG01718 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available DG01718 DGroup Drugs for addictive disorder ... DG01715 ... Drugs for nicotine dependence ... DG00994 ... Nicotine ... D03365 ... Nicotine (USP) ... D05156 ... Nicotine bitartrate (USAN) ... D05157 ... Nicotine polacrilex (USAN) ... DG00995 ... Varenicline ... D08669 ... Varenicline (INN) ... D06282 ... Varenicline tartrate (JAN/USAN) ... DG01716 ... Drugs for alcohol dependence ... DG00996 ... Acamprosate ... D07058 ... Acamprosate (INN) ... D02780 ... Acamprosate calcium (JAN/USAN) ... DG00997 ... Naltrexone ... D05113 ... Naltrexone (USAN/INN) ... D02095 ... Naltrexone hydrochloride (USP) ... DG00998 ... Nalmefene ... D05111 ... Nalmefene (USAN/INN) ... D02104 ... Nalmefene hydrochloride ... D10812 ... Nalmefene hydrochloride hydrate (JAN) ... DG01756 ... Ondelopran ... D10143 ... Ondelopran (USAN/INN) ... D10144 ... Ondelopran hydrochloride (USAN) ... D00123 ... Cyanamide (JP17) ... D00131 ... Disulfiram (JP17/USP/INN) ... D03288 ... Calcium carbimide (INN) DG01717 ... Drugs for opioid dependence ... DG00820 ... Buprenorphine ... D07132 ... Buprenorphine (JAN/INN) ... D00836 ... Buprenorphine hydrochloride (JP17/USP) ... DG00999 ... Methadone ... D08195 ... Methadone (BAN) ... D02102 ... Methadone hydrochloride (JAN/USP) ... DG01000 ... Levacetylmethadol ... D04716 ... Levomethadyl acetate (USAN); Levacetylmethadol (INN) ... D00840 ... Levomethadyl acetate hydrochloride (USAN) ... DG01001 ... Lofexidine ... D08141 ... Lofexidine (INN) ... D04765 ... Lofexidine hydrochloride (USAN) ... DG01002 ... Levomethadone ... D08121 ... Levomethadone (INN) ... D08122 ... Levomethadone hydrochloride ... DG01003 ... Diamorphine ... D07286 ... Diamorphine (BAN) ... D07810 ... Diacetylmorphine hydrochloride ... D10250 ... Buprenorphine - naloxone mixt ... DG01151 ... Nalorphine ... D08247 ... Nalorphine (INN) ... D08248 ... Nalorphine hydrochloride (USP) ... DG01155 ... Naloxone ... D08249 ... Naloxone (INN) ... D01340 ... Naloxone hydrochloride (JP17/USP

[The history of heroin].

Science.gov (United States)

Hosztafi, S

2001-08-01

The discovery of heroin and the development of heroin abuse are introduced. Heroin, the hydrochloride of diacetylmorphine, was discovered by acetylation of morphine. Heroin, in pharmacological studies, proved to be more effective than morphine or codeine. The Bayer Company started the production of heroin in 1898 on a commercial scale. The first clinical results were so promising that heroin was considered a wonder drug. Indeed, heroin was more effective than codeine in respiratory diseases. It has turned out, however, that repeated administration of heroin results in the development of tolerance and the patients become heroin-addicts soon. In the early 1910s morphine addicts "discovered" the euphorising properties of heroin and this effect was enhanced by intravenous administration. Heroin became a narcotic drug and its abuse began to spread quickly. Restrictions on its production, use and distribution were regulated by international treties. The total ban on heroin production was also proposed. As a result of the strict regulations the production and cosumption of heroin showed a significant decrease after 1931. At the same time the underworld recognized the shortage of heroin and started the illicit production and trafficking. The quantity of heroin seized by law enforcement agencies in the past decades rose gradually. As an indicator of the worldwide heroin market, the quantity of confiscated heroin underwent a tenfold increase since 1970. The paper surveys the most important heroin-producing and trafficking countries. Heroin, prepared in clandestine ("kitchen" or "jungle") laboratories, is diluted ("cut") by every member of the illegal heroin distributing chain, i.e. smugglers, traffickers, dealers and vendors.