tailieunhanh - báo cáo khoa học: "Methadone adverse reaction presenting with large increase in plasma methadone binding: a case series"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài:Methadone adverse reaction presenting with large increase in plasma methadone binding: a case series | Lu et al. Journal of Medical Case Reports 2011 5 513 http content 5 1 513 JOURNAL OF MEDICAL CASE REPORTS CASE REPORT Open Access Methadone adverse reaction presenting with large increase in plasma methadone binding a case series Wenjie J Lu1 Weidong Zhou2 Yvonne Kreutz3 and David A Flockhart1 3 Abstract Introduction The use of methadone as an analgesic is on the increase but it is widely recognized that the goal of predictable and reproducible dosing is confounded by considerable variability in methadone pharmacokinetics and unpredictable side effects that include sedation respiratory depression and cardiac arrhythmias. The mechanisms underlying these unpredictable effects are frequently unclear. Here to the best of our knowledge we present the first report of an association between accidental methadone overexposure and increased plasma protein binding a new potential mechanism for drug interactions with methadone. Case presentation We describe here the cases of two patients who experienced markedly different responses to the same dose of methadone during co-administration of letrozole. Both patients were post-menopausal Caucasian women who were among healthy volunteers participating in a clinical trial. Under the trial protocol both patients received 6 mg of intravenous methadone before and then after taking letrozole for seven days. One woman aged 59 experienced symptoms consistent with opiate overexposure after the second dose of methadone that were reversed by naloxone while the other aged 49 did not. To understand the etiology of this event we measured methadone pharmacokinetics in both patients. In our affected patient only a fourfold to eightfold increase in methadone plasma concentrations after letrozole treatment was observed. Detailed pharmacokinetic analysis indicated no change in metabolism or renal elimination in our patient but the percentage of unbound methadone in the plasma decreased . As a result the volume of