Comparative bioavailability of trazodone formulations using stable isotope methodology.

Abstract

The bioavailability of trazodone, a new antidepressant, from 50 mg dividose (A) or film‐sealed (B) tablets relative to an oral solution was determined in six healthy male subjects using 50 mg of D4‐trazodone as a stable isotope labelled standard. Concentrations of trazodone and D4‐trazodone were measured by GCMS. The pharmacokinetics of trazodone and D4‐trazodone were identical indicating no isotope effect. For formulation A, B and solution, the relative (trazodone/D4‐trazodone) Cmax values were 0.84 +/‐ 0.09, 0.90 +/‐ 0.05 and 1.05 +/‐ 0.04. The relative bioequivalence of the dosage formed with a power of 85% (power by conventional ANOVA was 54%). Among subjects % relative standard deviations (RSD) for the D4‐trazodone AUC values, a measure of intra‐ subject variability, were 6 to 38% while the % RSDs by period, a measure of inter‐subject variability, were 26 to 55%.