Summary
The steady-state pharmacokinetics and tolerability of the α1-adrenoceptor antagonist alfuzosin were investigated in 12 healthy male volunteers 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 except those related to the dose administered. The times to peak plasma concentrations (tmax) 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) tmax after the 3 doses on day 5 were: treatment A, 2.0 ± 0.2, 1.4 ± 0.1 and 2.3 ± 0.3h, and treatment B, 1.9 ± 0.1, 1.9 ± 0.2 and 1.8 ± 0.2h. Peak concentrations following the first two 2.5mg doses, identical in both treatment sequences, were also not significantly different: treatment A, 10.4 ± 0.7 and 12.0 ± 0.9 μg/L, treatment B, 11.5 ± 0.9 and 11.4 ±0.8 μg/L (mean ± SEM). Cmax following the 2000h dose was significantly different (p = 0.0004) and in direct proportion to the larger dose: treatment A, 13.9 ± 1.0 μg/L; treatment B, 22.6 ± 1.7 μg/L (mean ± SEM). Similarly, the area under the plasma concentration-time curve (AUC) was significantly (p = 0.0001) greater with the larger dose: treatment A, 184 ± 13 and treatment B, 244 ± 19 μg/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 reported headache, one subject experienced dizziness when standing on 2 occasions, and another subject reported experiencing dry mouth. All adverse events resolved without treatment.
Comparison of the 2 dosage regimens did not reveal any significant differences relating to haemodynamic parameters.
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Crome, P., Wijawardhana, P., Ankier, S.I. et al. Alfuzosin: A Comparison of the Steady-State Pharmacokinetics of Two Dosages in Middle-Aged and Elderly Healthy Male Volunteers. Drug Invest. 6, 156–161 (1993). https://doi.org/10.1007/BF03259736
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DOI: https://doi.org/10.1007/BF03259736