Pharmacokinetic comparison between fixed-dose combination of fimasartan/amlodipine 60/10 mg and the corresponding loose combination through partial replicated crossover study in healthy subjects
10.12793/tcp.2019.27.4.134
- Author:
Eunsol YANG
1
;
Soyoung LEE
;
Heechan LEE
;
Inyoung HWANG
;
In Jin JANG
;
Kyung Sang YU
;
SeungHwan LEE
Author Information
1. Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea. leejh413@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Amlodipine;
Fimasartan;
Fixed-dose combination;
Scaled bioequivalence;
Partial replicated crossover
- MeSH:
Amlodipine;
Antihypertensive Agents;
Cross-Over Studies;
Healthy Volunteers;
Hypertension;
Pharmacokinetics;
Plasma;
Therapeutic Equivalency
- From:Translational and Clinical Pharmacology
2019;27(4):134-140
- CountryRepublic of Korea
- Language:English
-
Abstract:
Combination therapies of antihypertensive drugs are recommended in cases where hypertension is not controlled by monotherapy. This study aimed to compare the pharmacokinetics (PKs) between fixed-dose combination (FDC) of fimasartan/amlodipine 60/10 mg and the corresponding loose combination. Because of the high intra-subject variability for maximum plasma concentration (C(max)) of fimasartan, a randomized, open-label, 3×3 partial replicated crossover design was adopted. Subjects received a single dose of FDC of fimasartan/amlodipine 60/10 mg or the corresponding loose combination in each period. Blood samples for PK analysis were collected up to 48 hours for fimasartan and 144 hours for amlodipine, respectively. Geometric mean ratios (GMRs) and its 90% confidence intervals (CIs) of the FDC to the loose combination for C(max) and area under the concentration-time curve from time 0 to the last quantifiable time point (AUC(last)) were calculated. Sixty healthy subjects were randomized, and 57 subjects completed the study. The concentration-time profiles of fimasartan and amlodipine were similar between the FDC and loose combination. The GMRs (90% CIs) of the FDC to the loose combination for C(max) and AUC(last) were 1.0440 (0.9202–1.1844) and 1.0412 (0.9775–1.1090) for fimasartan, and 1.0430 (1.0156–1.0711) and 1.0339 (1.0055–1.0631) for amlodipine, respectively. The GMRs and its 90% CIs for C(max) and AUC(last) of fimasartan and amlodipine were included not only in the scaled bioequivalence criteria but also in the conventional bioequivalence criteria. In conclusion, FDC of fimasartan/amlodipine 60/10 mg showed comparable PK profiles with the corresponding loose combination, which suggests their bioequivalence.
