title: Single dose methodology to assess the influence of an alpha1-adrenoceptor antagonist on uroflowmetric parameters in patients with benign prostatic hyperplasia.
abstract: OBJECTIVE
  To establish methodology which rapidly and reliably assesses the effect of an alpha1-adrenoceptor antagonist on peak urine flow rates in men with benign prostatic hyperplasia (BPH). This methodology could then be applied to screening new drugs to treat BPH.
  
  
  METHODS
  Twenty-five patients with BPH enrolled in a double-blind, placebo-controlled, two-period crossover study. Patients were either withdrawn from their current alpha1-adrenoceptor antagonist therapy (n = 22) or were untreated prestudy (n = 3) and all met prespecified uroflowmetric criteria including: (1) a peak urine flow rate (Qmax) < 12 ml s-1 off therapy (or < 10 ml s-1 if untreated prestudy) and (2) a decrease in peak urine flow rate (Qmax) 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 postdose (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 Qmax was 2.8 ml s-1 (P = 0.017 vs placebo). After 8 days dosing of tamsulosin, the least-square mean difference between tamsulosin and placebo in the change from baseline Qmax was also 2.8 ml s-1 (P = 0.044 vs placebo). Additionally, there was no significant difference observed between the single and multiple dose results (P > 0.200 for between group difference).
  
  
  CONCLUSIONS
  Both single and multiple doses of tamsulosin 0.4 mg increased Qmax in men with BPH. A single dose produced a comparable response to multiple dose administration. The magnitude of the effect was greater than the effect generally seen in longer term clinical trials, but this difference may be explained by the patient population in this study which was preselected for 'responsiveness' to an alpha1-adrenoceptor antagonist. These results support the utility of single dose uroflowmetric measurements in rapidly providing preliminary data on new investigational agents, specifically agents which act to increase urine flow in men with BPH. However, clinical efficacy would still need to be confirmed with longer term clinical trials.
authors.affiliation: Division of Clinical Pharmacology, Merck and Co., Rahway, NJ 07065, USA. sean_curtis@merck.com
authors.forename: S P
authors.initials: SP
authors.lastname: Curtis
authors.forename: I
authors.initials: I
authors.lastname: Eardley
authors.forename: M
authors.initials: M
authors.lastname: Boyce
authors.forename: P
authors.initials: P
authors.lastname: Larson
authors.forename: R
authors.initials: R
authors.lastname: Haesen
authors.forename: K
authors.initials: K
authors.lastname: Gottesdiener
authors.forename: B J
authors.initials: BJ
authors.lastname: Gertz
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000368:Aged; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000503:physiopathology; D018340:Receptors, Adrenergic, alpha-1; D012212:Rheology; D014554:Urination / Q000187:drug effects*
chemical_list: C547713:ADRA1A protein, human; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1