Methadone maintenance treatment and mortality in HIV-positive people who inject opioids in China.

Bull World Health Organ. 2013 Feb 1; 91(2): 93-101
Zhao Y, Shi CX, McGoogan JM, Rou K, Zhang F, Wu Z

To examine the effect of methadone maintenance treatment (MMT) on mortality in people injecting opioids who receive antiretroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV) infection in China.The study involved a nationwide cohort of 23?813 HIV-positive (HIV+) people injecting opioids who received ART between 31 December 2002 and 31 December 2011. Mortality rates and demographic, disease and treatment characteristics were compared in patients who received either ART and MMT or ART only. Factors associated with mortality were identified by univariate and multivariate analysis.Overall, 3057 deaths occurred during 41?959 person-years of follow-up (mortality: 7.3 per 100 person-years; 95% confidence interval, CI: 7.0-7.5). Mortality 6 months after starting ART was significantly lower with ART and MMT than with ART only (6.6 versus 16.9 per 100 person-years, respectively; P?HubMed – Methadone

New treatment gives hope to East Africa’s drug users.

Bull World Health Organ. 2013 Feb 1; 91(2): 89-90

The United Republic of Tanzania is the first mainland sub-Saharan country to launch a national methadone programme as part of its battle to fight the twin epidemics of heroin addiction and HIV infection. Fumbuka Ng’wanakilala reports.
HubMed – Methadone

The Glucuronidation of R- and S- Lorazepam: Human Liver Microsomal Kinetics, UDP-Glucuronosyltransferase Enzyme Selectivity, and Inhibition by Drugs.

Drug Metab Dispos. 2013 Apr 3;
Uchaipichat V, Suthisisang C, Miners JO

The widely used hypnosedative-anxiolytic agent R,S-lorazepam is cleared predominantly by conjugation with glucuronic acid in humans, but the enantioselective glucuronidation of lorazepam has received little attention. The present study characterized the kinetics of the separate R- and S- enantiomers of lorazepam by human liver microsomes (HLM) and by a panel of recombinant human UDP-glucuronosyltransferase (UGT) enzymes. Respective mean Km and Vmax values for R- and S- lorazepam by HLM were 29 ± 8.9 and 36 ± 10 ?M, and 7.4 ± 1.9 and 10 ± 3.8 pmol/min.mg. Microsomal intrinsic clearances were not significantly different, suggesting the in vivo clearances of R- and S- lorazepam are likely to be similar. Both R- and S- lorazepam were glucuronidated by UGT 2B4, 2B7, and 2B15, while R-lorazepam was additionally metabolized by the extra-hepatic enzymes UGT 1A7 and 1A10. Based on in vitro clearances and consideration of available in vivo and in vitro data, UGT2B15 is likely to play an important role in the glucuronidation of R- and S-lorazepam. However, the possible contribution of other enzymes and the low activities observed in vitro indicate that the lorazepam enantiomers are of limited use as substrate probes for UGT2B15. In order to identify potential drug-drug interactions, codeine, fluconazole, ketamine, ketoconazole, methadone, morphine, valproic acid, and zidovudine were screened as inhibitors of R- and S- lorazepam glucuronidation by HLM. Of these drugs, in vitro – in vivo extrapolation suggested that only ketoconazole had the potential to inhibit lorazepam clearance to a clinically significant extent.
HubMed – Methadone

Development of sensitization to methamphetamine in offspring prenatally exposed to morphine, methadone and buprenorphine.

Addict Biol. 2013 Apr 3;
Chiang YC, Hung TW, Ho IK

Heroin use among young women of reproductive age has drawn much attention around the world. However, there is lack of information on the long-term effects of prenatal exposure to opioids on their offspring. Our previous study demonstrated that prenatally buprenorphine-exposed offspring showed a marked change in the cross-tolerance to morphine compared with other groups. In the current study, this animal model was used to study effects of methamphetamine (METH)-induced behavioral sensitization in the offspring at their adulthood. The results showed no differences in either basal or acute METH-induced locomotor activity in any of the groups of animals tested. When male offspring received METH injections of 2?mg/kg, i.p., once a day for 5?days, behavioral sensitization was induced, as determined by motor activity. Furthermore, the distance and rate of development (slope) of locomotor activity and conditioned place preference induced by METH were significantly increased in the prenatally buprenorphine-exposed animals compared with those in other groups. The dopamine D1 R in the nucleus accumbens of the prenatally buprenorphine-exposed offspring had lower mRNA expression; but no significant changes in the ?-, ?-opioid, nociceptin, D2 R and D3 R receptors were noted. Furthermore, significant alterations were observed in the basal level of cAMP and the D1 R agonist enhanced adenylyl cyclase activity in the prenatally buprenorphine-exposed group. Overall, the study demonstrates that D1 R and its downregulated cAMP signals are involved in enhancing METH-induced behavioral sensitization in prenatally buprenorphine-exposed offspring. The study reveals that prenatal exposure to buprenorphine caused long-term effects on offspring and affected the dopaminergic system-related reward mechanism.
HubMed – Methadone

Related Methadone Clinics Information…

Comments are closed.