Pharmacokinetics and dose proportionality of three Tramadol Contramid OAD tablet strengths.

Author(s): Karhu D, El-Jammal A, Dupain T, Gaulin D, Bouchard S

Affiliation(s): Labopharm Inc., Laval, QC, Canada.

Publication date & source: 2007-09, Biopharm Drug Dispos., 28(6):323-30.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

A three-way crossover study in 27 human volunteers was conducted to characterize the pharmacokinetics and to assess the dose proportionality of 100 mg, 200 mg and 300 mg strengths of a novel once-a-day tramadol controlled-release tablet (Tramadol Contramid OAD) following single-dose administration. Serial blood samples were collected at predefined timepoints over a 48 h period 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. Following dose normalization and logarithmic transformation of concentration-dependent parameters, the results were compared using analysis of variance (ANOVA). The residual variability thereby obtained was used to construct 90% classical confidence intervals. The two one-sided tests procedure was used for all pairwise comparisons. Dose proportionality was concluded since the 90% CI for the ratio of geometric means was included in the acceptance range of 0.80-1.25 for all comparisons.