ALFUZOSIN - A COMPARISON OF THE STEADY-STATE PHARMACOKINETICS OF 2 DOSAGES IN MIDDLE-AGED AND ELDERLY HEALTHY MALE-VOLUNTEERS

The steady-state pharmacokinetics and tolerability of the alpha1-adren oceptor antagonist alfuzosin were investigated in 12 healthy male volu nteers aged 50 to 70 years using an open crossover design. Comparison of the pharmacokinetic profile in subjects receiving repeated doses of either 7.5 or 10 mg/day for 5 days did not reveal any differences exc ept those related to the dose administered. The times to peak plasma c oncentrations (t(max)) were not significantly different after sequence A (2.5mg at 0800, 1400 and 2000h) or sequence B (2.5mg at 0800, 1400 and 5mg at 2000h). The mean (+/- SEM) t(max) after the 3 doses on day 5 were: treatment A, 2.0 +/- 0.2, 1.4 +/- 0.1 and 2.3 +/- 0.3h, and tr eatment B, 1.9 +/- 0.1, 1.9 +/- 0.2 and 1.8 +/- 0.2h. Peak concentrati ons following the first two 2.5mg doses, identical in both treatment s equences, were also not significantly different: treatment A, 10.4 +/- 0.7 and 12.0 +/- 0.9 mug/L, treatment B, 11.5 +/- 0.9 and 11.4 +/- 0. 8 mug/L (mean +/- SEM). C(max) following the 2000h dose was significan tly different (p = 0.0004) and in direct proportion to the larger dose : treatment A, 13.9 +/- 1.0 mug/L; treatment B, 22.6 +/- 1.7 ug/L (mea n +/- SEM). Similarly, the area under the plasma concentration-time cu rve (AUC) was significantly (p = 0.0001) greater with the larger dose: treatment A, 184 +/- 13 and treatment B, 244 +/- 19 mug/L/h (mean +/- SEM). The ratio of the AUC values obtained following treatments A and B was 77.9 +/- 2.5%, which corresponds to the ratio between the total dosages of treatments A and B, i.e. 75%. Five of the 12 subjects who completed the study reported one adverse event each. Three subjects re ported headache, one subject experienced dizziness when standing on 2 occasions, and another subject reported experiencing dry mouth. All ad verse events resolved without treatment. Comparison of the 2 dosage re gimens did not reveal any significant differences relating to haemodyn amic parameters.