Comparative bioavailability of two once-daily tramadol HCl 200 mg extended-release products in healthy volunteers

An open-label, randomized, 2-way crossover study was conducted to compare the pharmacokinetics of Tramadol Contramid(R) OAD 200 mg tablets and Monocrixo(R) L.P. 200 mg capsules following single-dose administration under fasting conditions in 30 healthy adult volunteers. Serial blood samples were collected at predefined time points over 48 hours post-dose and racemic tramadol and O-desmethyltramadol concentrations in plasma were determined using a validated LC-MS/MS method. Pharmacokinetic parameters were derived using noncompartmental methods. Results were compared using an analysis of variance (ANOVA) and the bioequivalence determination was based on the 90% confidence intervals for C-max, AUC(0-t) and AUC(0-infinity). Although the two products were determined to be bioequivalent with respect to C-max and AUC, the time to reach peak tramadol concentrations was significantly earlier for Tramadol Contramid(R) OAD (6 hours vs. 10 hours). A mean tramadol concentration of 100 ng/ml was attained within 1 hour for Tramadol Contramid(R) OAD compared with > 4 hours for Monocrixo(R) L.P. Both products were well tolerated.