Pharmacokinetics of a sustained-release dosage form of clomipramine

In this study, the pharmacokinetic parameters of the sustained-release (SR) dosage form of clomipramine (CMI) rvere compared with those obtained after the administration of the immediate- release (IR) dosage form. Two studies were per formed. In the first study, a single oral dose of both products w as administered in 12 healthy volunteers, and in the second study, multiple doses of both products rvere administered in 6 patients with depression in which steady-state plasma levels (C-ss) were determined. Plasma levels rs ere assayed using an HPLC method. In the single-dose study, the mean C-max and AUC values of CMI were 63.37 ng/mL(-1) and 1375.38 ng(.)h/ml(-1) for th e reference product and 32.55 ng/mL(-1) and 1285.26 ng(.)h/ml(-1) for the t est product, respectively. The mean beta and MRT values of GMI were 0.030 h (-1) and 47.21 h for the reference product and 0.026 h(-1) and 55.63 h for test product, respectively. Results showed that after the multiple-dose stu dy, the mean clomipramine plus demethylclomipramine values of C-sigmav(ss) were 406.2 ng/mL(-1) for the reference and 328.6 ng/mL(-1) for the sustaine d-release dosage form. This product also presented less fluctuation in stea dy-state plasma levels (1.08 vs. 1.23). The values of MRT and t(max) were h igher for the SR dosage form, showing that the drug was maintained longer i n the body. The mean values for the ratio metabolite/drug were 2.06 and 2.4 1 for the IR and SR dosage forms, respectively. Neither AUC nor elimination half-life was affected significantly after the administration of the susta ined-release dosage form. (C)2000 the American College of Clinical Pharmaco logy.