| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Chu, Nannan Xu, Hongrong Wang, Guoqin Wang, Jiangdian Chen, Weili Yuan, Fei Yang, Mengjie Li, Xuening |
| Description |
Country affiliation: China Author Affiliation: Chu N ( Department of Clinical Pharmacology, ZhongShan Hospital, Fudan University, Shanghai, China.); Xu H ( Department of Clinical Pharmacology, ZhongShan Hospital, Fudan University, Shanghai, China.); Wang G ( Clinical Research, MSD Asia R&D, Beijing, China.); Wang J ( Early Development Statistics, Biostatistics and Research Decision Sciences, Asia Pacific, MSD R&D, Beijing, China.); Chen W ( Department of Clinical Pharmacology, ZhongShan Hospital, Fudan University, Shanghai, China.); Yuan F ( Department of Clinical Pharmacology, ZhongShan Hospital, Fudan University, Shanghai, China.); Yang M ( Department of Clinical Pharmacology, ZhongShan Hospital, Fudan University, Shanghai, China.); Li X ( Department of Clinical Pharmacology, ZhongShan Hospital, Fudan University, Shanghai, China. Electronic address: li.xuening@zs-hospital.sh.cn.) |
| Abstract |
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(τ,ss) and C(max,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 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(τ,ss) and C(max,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(0-t) and C(max) values of tamsulosin for a single dose of coadministration of finasteride and tamsulosin hydrochloride and tamsulosin hydrochloride alone were 1.04 (0.97-1.10) 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. 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. |
| File Format |
HTM / HTML |
| ISSN |
01492918 |
| Issue Number |
2 |
| Volume Number |
37 |
| e-ISSN |
1879114X |
| Journal |
Clinical Therapeutics |
| Language |
English |
| Publisher |
Elsevier |
| Publisher Date |
2015-02-01 |
| Publisher Place |
United States |
| Access Restriction |
One Nation One Subscription (ONOS) |
| Subject Keyword |
Discipline Pharmacology Finasteride Pharmacokinetics Sulfonamides Urological Agents Adult Area Under Curve Asian Continental Ancestry Group Capsules Cross-over Studies Delayed-action Preparations Drug Combinations Drug Interactions Administration & Dosage Adverse Effects Blood Healthy Volunteers Humans Male Middle Aged Tandem Mass Spectrometry Methods Young Adult Journal Article Randomized Controlled Trial Research Support, Non-u.s. Gov't |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Pharmacology Pharmacology (medical) |
