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KMID : 1038020170250040190
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Translational and Clinical Pharmacology
2017 Volume.25 No. 4 p.190 ~ p.195
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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
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Choi Young-Kyung
Park Sung-Eun
Kim Eun-Young
Park Hyo-Ju
Kim Eun-Ji
Song Geun-Seog
Ghim Jong-Lyul
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Abstract
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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 ana-lyzed using a validated liquid chromatography tandem mass-spectrometry. A non-compartmental analysis was used to calculate pharmacokinetic (PK) variables and analysis of variance was per-formed 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 fol-lowing 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.
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KEYWORD
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Pharmacokinetics, Fixed-dose combination, atorvastatin, metformin extended release
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