Single dose methodology to assess the influence of an alpha(1)-adrenoceptor antagonist on uroflowmetric parameters in patients with benign prostatic hyperplasia

Aims To establish methodology which rapidly and reliably assesses the effec t of an alpha(1)-adrenoceptor antagonist on peak urine flow rates in men wi th benign prostatic hyperplasia (BPH). This methodology could then be appli ed to screening new drugs to treat BPH. Methods Twenty-five patients with BPH enrolled in a double-blind, placebo-c ontrolled, two-period crossover study. Patients were either withdrawn from their current alpha(1)-adrenoceptor antagonist therapy (n = 22) or were unt reated prestudy (n = 3) and all met prespecified uroflowmetric criteria inc luding: (1) a peak urine flow rate (Q(max)) < 12 ml s(-1) off therapy (or < 10 ml s(-1) if untreated prestudy) and (2) a decrease in peak urine flow r ate (Q(max)) of > 2 ml s(-1) after withdrawal from therapy. Study treatment consisted of tamsulosin 0.4 mg (or matching placebo) once daily for 8 days in a two-period crossover. Uroflowmetry was performed predose and once pos tdose (4.5-5.5 h postdose) on day 1, and once postdose (4.5-5.5 h postdose) on day 8 of each treatment period. Results After a single dose of tamsulosin, the least-square mean difference between tamsulosin and placebo in the change from baseline Q(max) was 2.8 ml s(-1) (P = 0.017 vs placebo). After 8 days dosing of tamsulosin, the lea st-square mean difference between tamsulosin and placebo in the change from baseline Q(max) was also 2.8 ml s(-1) (P = 0.044 vs placebo). Additionally , there was no significant difference observed between the single and multi ple dose results (P > 0.200 for between group difference). Conclusions Both single and multiple doses of tamsulosin 0.4 mg increased Q (max) in men with BPH. A single dose produced a comparable response to mult iple dose administration. The magnitude of the effect was greater than the effect generally seen in longer term clinical trials, but this difference m ay be explained by the patient population in this study which was preselect ed for 'responsiveness' to an alpha(1)-adrenoceptor antagonist. These resul ts support the utility of single dose uroflowmetric measurements in rapidly providing preliminary data on new investigational agents, specifically age nts which act to increase urine flow in men with BPH. However, clinical eff icacy would still need to be confirmed with longer term clinical trials.