Comparative Biopharmaceutical Performance of Imipramine Formulations in Man

Publisher Website
Google Scholar
Abstract
The systemic availability of an investigational liquid formulation of the tricyclic antidepressant imipramine was compared to that of a commercially available tablet (Tofranil) whose therapeutic efficacy was established by usage. The experiment was conducted under controlled conditions and a balanced 2-by-2 crossover design was used to dissociate the significance of formulation effects from subject, group and experimental period sources of variation. Pharmacokinetic interpretation and statistical analysis of plasma concentrations as a function of time and of systemic availability indicators reveal a nearly identical biopharmaceutical behavior for the 2 preparations. Significant differences (P < 0.05) were found in the cumulative area under the plasma concentration-time curve (AUC) up to 4 h after administration and the availability lag time, but not in the maximum plasma concentration, the time at which this concentration is reached, the 1st-order availability rate constant, and the AUC to infinity. These results collectively indicate a very similar biopharmaceutical performance, where the differences in the early AUC values are partly attributable to a longer availability lag time for the tablet formulation.