12 research outputs found
Specimen handling in an HPLC determination of phenylbutazone and its major metabolites in plasma, avoiding degradation of the compounds
Shosaikoto (a Kampo medicine) modulates changes in cytochrome P450 caused by Mycobacterium butyricum injection
Use of Lymphocytes for Assessing Ethanol-Mediated Alterations in the Expression of Hepatic Cytochrome P4502E1
Steady-state pharmacokinetics of (R)- and (S)-methadone in methadone maintenance patients
AimsTo investigate the steady-state pharmacokinetics of (R)- and (S)-methadone in a methadone maintenance population.MethodsEighteen patients recruited from a public methadone maintenance program underwent an interdosing interval pharmacokinetic study. Plasma and urine samples were collected and analysed for methadone and its major metabolite (EDDP) using stereoselective h.p.l.c. Methadone plasma protein binding was examined using ultrafiltration, and plasma alpha1-acid glycoprotein concentrations were quantified by radial immunoassay.Results(R)-methadone had a significantly (P 0.2) differences between the methadone enantiomers for AUCtauss, steady-state plasma clearance, trough plasma concentrations and unbound renal clearance. Patients excreted significantly (P ConclusionsSteady-state pharmacokinetics of unbound methadone are stereoselective, and there is large interindividual variability consistent with CYP3A4 mediated metabolism to the major metabolite EDDP; the variability did not obscure a significant dose-plasma concentration relationship. Stereoselective differences in the pharmacokinetics of methadone may have important implications for pharmacokinetic-pharmacodynamic modelling but is unlikely to be important for therapeutic drug monitoring of methadone, in the setting of opioid dependence