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

Purpose: The 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. Methods: This 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. Findings: Fifteen subjects were enrolled, and 14 completed the study. The geometric mean ratios (GMRs) (90% CIs) of AUC(tau,s)s and C-max,C-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 1106 (0.99-1.14), respectively. The GMRs (90% CIs) for AUC(0,t) and C-max 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 AUC(tau,s)s and C-max,C-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 AUC(tau,s)s and C-max values of tamsulosin for a single dose of coadministration of finasteride and tamsulosin hydrochloride and tamsulosin hydrochloride alone were 1.04 (0.97-140) 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. Implications: Both 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. (C) 2015 Elsevier HS Journals, Inc. All rights reserved.