Bioavailability and kinetics of maprotiline

Abstract

Male human subjects (6) received simultaneously single 50-mg oral doses of a maprotiline hydrochloride tablet (an antidepressant) and a trideuterated maprotiline hydrochloride aqueous solution. No side effects or other problems were encountered. The blood levels of unlabeled and isotope-labeled maprotiline for each subject were essentially superimposable. Peak levels, averaging about 50 ng/ml, were attained between 8-24 h after drug. The biologic t1/2 [half-life] (.beta.-phase) averaged 58 h for the unlabeled and 60.5 h for the labeled drug. The total areas under the curves (extended to time infinity) averaged 3862 and 3944 ng h/ml for maprotiline and trideuterated maprotiline, respectively (differences between the two are not significant). At the 95% degree of confidence the Westlake confidence limits show less than 10% differences between the formulations with respect to area under the curve data (calculated both to 168 h and extended to time infinity), peak blood levels and biologic t1/2. There were no differences between formulations with respect to times of peak concentrations. Estimates were made for apparent volumes of distribution (about 1000 l), apparent blood clearance (about 14 l/h), lag times (about 1.42 h for tablets and 1.31 h for solution), and absorption rate constants (about 0.34/h for the tablets and 0.42/h for the solution).