Pharmacokinetic Interaction of Finasteride With Tamsulosin Hydrochloride: An Open-label, Randomized, 3-period Crossover Study in Healthy Chinese Male Volunteers

Abstract

PurposeThe primary aim of this study was to evaluate whether there was clinically significant pharmacokinetic (PK) interaction between finasteride and tamsulosin in healthy Chinese male subjects. MethodsThis was an open-label, randomized, 3-period, crossover study. Subjects received single and multiple doses of 5 mg finasteride alone, single and multiple doses of 0.2 mg tamsulosin hydrochloride sustained-release capsule alone, and single and multiple doses of 5 mg finasteride with 0.2 mg tamsulosin hydrochloride, in an order determined by a computerized randomization schedule. Blood samples were collected up to 48 hours after dosing on study day 1 and up to 24 hours after dosing on study day 9 for determination of plasma concentrations with a validated LC-MS/MS method. Pharmacokinetic parameters were estimated via noncompartmental methods. Tolerability was evaluated by monitoring adverse events, laboratory assays, vital signs, and 12-lead ECG. FindingsFifteen subjects were enrolled, and 14 completed the study. The geometric mean ratios (GMRs) (90% CIs) of AUCτ,ss and Cmax,ss values of finasteride at steady state between coadministration of finasteride and tamsulosin hydrochloride and finasteride alone were 1.14 (1.05–1.23) and 1.06 (0.99–1.14), respectively. The GMRs (90% CIs) for AUC0–t and Cmax values of finasteride for a single dose of coadministration of finasteride and tamsulosin hydrochloride and finasteride alone were 1.02 (0.94–1.11) and 1.06 (1.01–1.11), respectively. The GMRs (90% CIs) for AUCτ,ss and Cmax,ss values of tamsulosin at steady-state for coadministration of finasteride and tamsulosin hydrochloride and tamsulosin hydrochloride alone were 1.18 (1.05–1.33) and 1.23 (1.06–1.43), respectively. The GMRs (90% CIs) for AUC0–t and Cmax values of tamsulosin for a single dose of coadministration of finasteride and tamsulosin hydrochloride and tamsulosin hydrochloride alone were 1.04 (0.97–1.10) and 1.04 (0.98–1.11), respectively. Statistical analyses confirmed that the 90% CIs for these PK parameters were within the predefined not clinically significant PK drug-drug interaction effect boundaries (0.5–2.0) in this study. If comparing the findings with narrower boundaries (0.8–1.25), the conclusion may not be supportive for tamsulosin hydrochloride. During the study, a total of 4 adverse events were reported in 3 subjects including allergic reaction, abnormal findings on an ECG, a slight increase in alanine aminotransferase, and a positive result on glucose urine test. ImplicationsBoth finasteride and tamsulosin hydrochloride were well tolerated. Coadministration of finasteride and tamulosin hydrochloride seems unlikely to lead to a clinically significant PK drug-drug interaction, after a single dose and at steady state.