Pharmacokinetics of atorvastatin and sustained-release metformin fixed-dose combination tablets: two randomized, open-label, 2-way crossover studies in healthy male subjects under fed conditions.
10.12793/tcp.2017.25.4.190
- Author:
Young Kyung CHOI
1
;
Sung Eun PARK
;
Eun Young KIM
;
Hyo Ju PARK
;
Eun Ji KIM
;
Geun Seog SONG
;
Jong Lyul GHIM
Author Information
1. Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan 47392, Republic of Korea.
- Publication Type:Original Article
- Keywords:
Pharmacokinetics;
Fixed-dose combination;
atorvastatin;
metformin extended release
- MeSH:
Atorvastatin Calcium*;
Chromatography, Liquid;
Cross-Over Studies*;
Humans;
Male*;
Metformin*;
Patient Compliance;
Pharmacokinetics*;
Plasma;
Tablets*;
Therapeutic Equivalency
- From:Translational and Clinical Pharmacology
2017;25(4):190-195
- CountryRepublic of Korea
- Language:English
-
Abstract:
Two separate studies were conducted to establish bioequivalence (BE) for two doses of atorvastatin/metformin sustained-release (SR) fixed dose combination (FDC) versus the same dosage of the individual component (IC) tablets in healthy male subjects under fed conditions (study 1, BE of atorvastatin/metformin SR 20/500 mg FDC; study 2, BE of atorvastatin/metformin SR 20/750 mg FDC). Each study was a randomized, open-label, single oral dose, two-way crossover design. Serial blood samples were collected pre-dose and up to 36 hours post-dose for atorvastatin and 24 hours for metformin. Plasma concentrations of atorvastatin, 2-OH atorvastatin and metformin were analyzed using a validated liquid chromatography tandem mass-spectrometry. A non-compartmental analysis was used to calculate pharmacokinetic (PK) variables and analysis of variance was performed on the lognormal-transformed PK variables. A total of 75 subjects completed the study 1 (36 subjects) and study 2 (39 subjects). The 90% confidence intervals for the adjusted geometric mean ratio of Cmax and the AUC0-t were within the predefined 0.80 to 1.25 range. The number of subjects reporting at least one adverse event following FDC treatments was comparable to that following IC treatments. The two treatments were well tolerated. Therefore, atorvastatin/metformin SR 20/500 mg and 20/750 mg FDC tablets are expected to be used as alternatives to IC tablets to decrease the pill burden and increase patient compliance.
