[Replacement Therapy as a Method to Promote Social and Professional Re-Adaptation.]
[Replacement Therapy as a Method to Promote Social and Professional Re-Adaptation.]
Gesundheitswesen. 2013 Jan 8;
Rotter I, Król-Pakulska E, Radli?ska I, Mroczek B, Grochans E, Pakulski C, Karakiewicz B
The aim of this work is to assess the impact of replacement therapy on social and professional re-adaptation of people addicted to opioids.This study covered 82 patients (52 male, 30 female; mean age of 39.9 years) addicted to opioids and treated with methadone. An analysis of medical records served as a research method.Participation in the methadone programme influenced taking up a job by 47.5% of addicted; improving the legal situation, i.?e., reduction of the number of criminal cases for 42.7% of addicted; and the feeling of positive impact on social re-adaptation by 96.3% of addicted.Replacement therapy with methadone fosters professional activation, reduces criminality and gives a feeling of social re-adaptation for people addicted to opioids.
HubMed – Methadone
Haplotypes frequencies of CYP2B6 in Malaysia.
J Postgrad Med. 2012 Oct; 58(4): 235-41
Musa N, Zulkafli MI, Talib N, Mohamad N, Fauzi H, Ismail R
Background: Drugs with complex pharmacology are used in the management of drug use disorder (DUD) and HIV/AIDS in Malaysia and in parts of South-East Asia. Their multiethnic populations suggest complexity due to the genetic polymorphism, such as CYP2B6 that metabolizes methadone and anti-retroviral. Aims: Our aim was to explore the genetic polymorphism of CYP2B6 among Malays, Chinese, Indians, and opiate-dependent individuals in Malaysia. Settings and Design: The study utilized DNA from our previous studies on CYPs and new recruitments from opiate-dependent individuals. Materials and Methods: For the new recruitment, after obtaining consent and baseline demography, 5 ml blood was obtained from patients attending methadone maintenance therapy (MMT) Clinics. Genomic DNA was extracted using standard methods. 10 nucleotide changes associated with CYP2B6FNx0110, CYP2B6FNx012, CYP2B6FNx0117, CYP2B6FNx0111, CYP2B6FNx018, CYP2B6FNx0114, CYP2B6FNx019, CYP2B6FNx014, CYP2B6FNx016, CYP2B6FNx0127, and CYP2B6FNx0120 were determined using multiplex nested allele-specific PCR. Statistical Analysis: Descriptive statistics were used to summarize demographic data. Differences in allele frequencies between populations were tested using Chi-squared test and were corrected using the Bonferroni test. Results: CYP2B6 polymorphism in Malaysia is variable with trends that suggest an ethnic difference. Reduced activity CYP2B6FNx016 occurred in 13% to 26% among Malays, Chinese, Indians and opiate-dependent individuals. Another ‘reduced activity’, CYP2B6FNx012 allele, was found at much lower percentages in the groups. Conclusions: The relative commonness of reduced-activity CYP2B6 alleles in our study called for attention in terms of dosage requirements for MMT and ARV in Malaysia. It also implored follow-up association studies to determine its relevance and consequences in personalized medicine for drug use disorder and HIV/AIDS.
HubMed – Methadone
Methadone N-demethylation by the Common CYP2B6 Allelic Variant CYP2B6.6.
Drug Metab Dispos. 2013 Jan 8;
Gadel S, Crafford A, Regina K, Kharasch E
The long-acting opioid methadone displays considerable unexplained interindividual pharmacokinetic variability. Methadone metabolism clinically occurs primarily by N-demethylation to 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), catalyzed predominantly by cytochrome P450 2B6 (CYP2B6). Retrospective studies suggest an influence of the common allele variant CYP2B6*6 on methadone plasma concentrations. The catalytic activity of CYP2B6.6, encoded by CYP2B6*6, is highly substrate-dependent. This investigation evaluated methadone N-demethylation by CYP2B6.6, and in comparison to that by wild-type CYP2B6.1. Methadone enantiomer and racemate N-demethylation by recombinant expressed CYP2B6.6 and CYP2B6.1 was determined. At substrate concentrations (0.25-2 ?M) approximating plasma concentrations occurring clinically, rates of methadone enantiomer N-demethylation by CYP2B6.6, incubated individually or as the racemate, were one-third to one-fourth those by CYP2B6.1. For methadone individual enantiomers metabolism by CYP2B6.6 compared with CYP2B6.1, V(max) was diminished, K(s) was greater, the in vitro intrinsic clearance was diminished 5- to 6-fold. The intrinsic clearance for R- and S-EDDP formation from racemic methadone was diminished approximately 6-fold and 3-fold for R- and S-methadone. Both CYP2B6.6 and CYP2B6.1 showed similar stereoselectivity (S>R-methadone). Human liver microsomes with diminished CYP2B6 content due to a CYP2B6*6 allele had lower rates of methadone N-demethylation. Results show that methadone N-demethylation catalyzed by CYP2B6.6, the CYP2B6 variant encoded by the CYP2B6*6 polymorphism, is catalytically deficient compared with wild-type CYP2B6.1. Diminished methadone N-demethylation by CYP2B6.6 may provide a mechanistic explanation for clinical observations of altered methadone disposition in individuals carrying the CYP2B6*6 polymorphism.
HubMed – Methadone
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