Pharmacokinetic Drug Interaction Between Amlodipine and Tadalafil: An Open-Label, Randomized, Multiple-Dose Crossover Study in Healthy Male Volunteers.

Content Provider	Europe PMC
Author	Kim, Hyungsub Lee, Shi Hyang Jung, Jina Hong, Sunghee Lim, Hyeong-Seok
Copyright Year	2022
Abstract	PurposeThe combined administration of tadalafil, a phosphodiesterase-5 inhibitor, and amlodipine, a calcium channel blocker, can be a promising therapeutic option for hypertension patients with erectile dysfunction. This study aimed to examine the pharmacokinetic drug interaction between tadalafil and amlodipine and the tolerability of their combined administration in healthy male subjects.Subjects and MethodsHealthy volunteers (N = 24) were randomly assigned to one of the six sequences that consisted of three treatments: tadalafil (5 mg) alone, amlodipine (10 mg) alone, and tadalafil plus amlodipine. The study drugs were administered orally for 9 d, and the collected serial blood samples were analyzed up to 72 h after the last dosing. Pharmacokinetic parameters were calculated using non-compartmental analysis.ResultsFor tadalafil, geometric mean ratios (GMRs) (90% confidence interval (CI)) of the combined therapy over the monotherapy were 1.57 (1.46–1.68) for AUCτ,ss and 1.34 (1.24–1.45) for Cmax,ss. For amlodipine, the GMRs (90% CI) of AUCτ,ss and Cmax,ss were 0.93 (0.90–0.97) and 0.95 (0.91–0.99), respectively. The severity of all observed adverse events (AEs) related to the study drugs was mild, and the frequency of AEs of the combined administration was not significantly different from the monotherapy.ConclusionA substantial pharmacokinetic drug interaction between tadalafil and amlodipine was observed with respect to the concentration of tadalafil when administered concomitantly. However, the dose range of the combined administration of tadalafil and amlodipine in the present study was well tolerated by the subjects.
Page Count	9
Volume Number	16
PubMed Central reference number	PMC8865872
PubMed reference number	35221673
Journal	Drug Design, Development and Therapy [Drug Des Devel Ther]
e-ISSN	11778881
DOI	10.2147/DDDT.S348897
Language	English
Publisher	Dove
Publisher Date	2022-02-19
Access Restriction	Open
Rights License	This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). © 2022 Kim et al.
Subject Keyword	drug interaction tadalafil amlodipine pharmacokinetics tolerability
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Pharmaceutical Science Pharmacology