Pharmacokinetics and safety of tamsulosin in subjects with normal and impaired renal or hepatic function

Background: Tamsulosin is a potent alpha(1)-adrenergic receptor antagonist used in the treatment of benign prostatic hyperplasia. Objective: The purpose of these studies was to assess the pharmacokinetics and safety of tamsulosin in subjects with normal and impaired renal or hepa tic function. Methods: In the first study, the pharmacokinetic profile of tamsulosin was compared in 12 subjects with renal function impairment and 6 with normal re nal function. The second study was carried out in 8 subjects with hepatic i nsufficiency and 8 with normal hepatic function, Plasma and urine data were analyzed, and the effects of clinical and biochemical variables on pharmac okinetic parameters were evaluated. Results: Subjects with renal impairment had higher levels of alpha(1)-acid glycoprotein (alpha (1)-AGP) than those with normal renal function, and tho se with impaired liver function had lower levels than subjects with normal liver function. Since tamsulosin is highly bound to alpha (1)-AGP in vivo, these variations affected the levels of unbound fraction (f(u)) of the drug . In renally impaired subjects, f(u) was reduced in comparison with normal subjects, and was significantly increased in those with impaired hepatic fu nction. These results correlated significantly with the total apparent clea rance of the drug, whereas parameters indicative of renal or hepatic functi on did not. Conclusions: The results of the 2 studies indicate that the pharmacokinetic s and safety profile of tamsulosin are not significantly influenced by rena l or hepatic function. This suggests that no dose adjustment of tamsulosin is necessary in patients with renal or hepatic insufficiency.