Effect of concomitant administration of cimetidine hydrochloride on the pharmacokinetic and safety profile of tamsulosin hydrochloride 0.4 mg in healthy subjects

Background: Tamsulosin is an α₁-adrenergic receptor antagonist that is metabolized primarily via the cytochrome P450 (CYP450) enzymes. Cimetidine hydrochloride is a histamine H₂-receptor antagonist that is known to inhibit the activity of CYP enzymes.Objective: The purpose of this nonrandomized, sequential, drug-drug interaction study was to determine whether concomitant administration of cimetidine affects the pharmacokinetic and safety profile of tamsulosin 0.4 mg in healthy subjects.Methods: In this 11-day study, 10 healthy subjects aged 21 to 38 years received a single daily dose of placebo except on study days 2 and 8, when they received tamsulosin 0.4 mg. From day 5 through day 10, subjects also received a single oral tablet of cimetidine 400 mg every 6 hours. Safety monitoring was performed throughout the study. Plasma tamsulosin concentrations were determined at regular intervals after administration of the drug on days 2 and 8, and tamsulosin pharmacokinetic parameters were tested for equivalence on these 2 days.Results: Oral clearance of tamsulosin was significantly reduced (P < 0.004), and area under the plasma concentration—time curve extrapolated to infinity (AUC_0−∞) significantly increased (P < 0.004) during concomitant administration of cimetidine. However, the observed increase in AUC_0−∞ was not expected to be clinically important since tamsulosin is well tolerated at twice the dose used in this study. Some significant changes in vital signs (ie, diastolic blood pressure <60 mm Hg) and a number of mild adverse events such as headache were observed, but the overall safety profile of tamsulosin plus cimetidine was acceptable.Conclusions: The results of this pharmacokinetic study were likely due to inhibition by cimetidine of CYP450 isozymes that catalyze tamsulosin metabolism. Although this study was conducted in young, healthy volunteers, thereby limiting the conclusions that can be drawn, the results, taken in the context of similar studies conducted in the target population, do not suggest that dose adjustment of tamsulosin is necessary in patients concurrently receiving cimetidine therapy.