Alfuzosin, an alpha1-adrenoceptor antagonist for the treatment of benign prostatic hyperplasia: once daily versus 3 times daily dosing in healthy subjects.

Abstract

A new patented prolonged release formulation of the alpha1-adrenoceptor antagonist alfuzosin has been developed for once-daily (OD) administration in benign prostatic hyperplasia (BPH). This study was designed to compare 2 dose regimens: 10 mg OD alfuzosin and 2.5 mg TID alfuzosin at steady state. In an open, randomized crossover study with a 9-day washout between treatments, 18 healthy male subjects (50 - 65 years) received OD or TID alfuzosin tablets orally over 5 days. Both formulations were administered according to the schedule recommended for therapeutic use: OD was administered 5 min after the evening meal, TID was administered in the evening, then in the morning and at noon (30 min before meals). On the fifth day, plasma concentrations were quantitated by HPLC with spectrofluorometric detection. The following pharmacokinetic parameters refer to the geometric mean values for both formulations. Mean Cmax value of 10 mg OD alfuzosin was 15.8 ng/ml at a median t(max) of 9.0 h; Cmax was higher and reached earlier from 2.5 mg alfuzosin TID: 19.3 ng/ml, 19.7 ng/ml and 20.3 at 1.0 hour after each dosing, respectively. Mean AUC(0-24) values after OD and TID were 228.3 and 226.0 ng x h/ml, respectively. Based on AUC(0-24) values corrected by the administered daily dose, the relative bioavailability of alfuzosin OD was 75.7% with a 90% confidence interval of 68.0 - 84.3%. Non-corrected AUC(0-24) values were bioequivalent with a ratio estimate of 101.0% and a 90% confidence interval of 90.7 - 112.5%. The higher daily dose compensated for the loss of bioavailability observed with the OD formulation. Mean t1/2z value was longer for the OD (8.9 h) than the TID formulation (6.9 h). Variability between individuals was similar for the 2 formulations. Both dose regimens were well tolerated. Alfuzosin 10 mg once-daily provides a suitable pharmacokinetic profile for a once-daily administration, equivalent bioavailability between the 2 dosage regimens and a good safety profile justify the use of alfuzosin 10 mg in patients with BPH.