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Implementation of a reference-scaled average bioequivalence approach for highly variable generic drug products of atorvastatin in Chinese subjects

Authors: Su-Mei Xu; Juan Yan; Dai Li; Dan Li; Xiao-Min Li; Ping-Sheng Xu;

Implementation of a reference-scaled average bioequivalence approach for highly variable generic drug products of atorvastatin in Chinese subjects

Abstract

OBJECTIVE The purpose of this study was to evaluate the bioequivalence of two formulations of atorvastatin using the reference-scaled average bioequivalence (RSABE) method and to study the pharmacokinetics of atorvastatin in healthy Chinese subjects under fed conditions. MATERIALS AND METHODS A single-dose, randomized, open-label, four-way crossover study was conducted in healthy Chinese subjects after informed consent was obtained. Healthy subjects were randomly assigned to receive 20 mg of either the test or reference formulation, following a 7-day washout period. The formulations were considered bioequivalent if 90% confidence intervals (CIs) for the ln-transformed ratios and ratio of geometric means (GMR) of AUC and Cmax of atorvastatin were within the bioequivalence range (80 - 125%). Plasma atorvastatin, ortho-hydroxy atorvastatin and para-hydroxy atorvastatin concentrations were analyzed by liquid chromatography-tandem mass spectrometry. Tolerability was assessed during the entire study period. RESULTS ANOVA indicated that the period, sequence, and formulation had no significant effect on the pharmacokinetic parameters (p < 0.05). The test formulation was bioequivalent to the marketed formulation as the 90% CIs for natural log-transformed ratios of atorvastatin of Cmax (88.45 - 103.57%), AUC0-t (98.08 - 104.89%) and AUC0-∞ (98.15 - 104.87%) were within equivalence limits (80 - 125%). No serious adverse events were found among the subjects. CONCLUSION The RSABE approach was successful in evaluating the bioequivalence of these two formulations. This study confirmed that test and reference atorvastatin calcium tablets were bioequivalent under fed condition.

Subjects by Vocabulary

Microsoft Academic Graph classification: Atorvastatin Cmax Pharmacology Bioequivalence Pharmacokinetics Generic drug medicine business.industry Crossover study Confidence interval Tolerability business medicine.drug

Keywords

Administration, Oral, Biological Availability, Atorvastatin, Drugs, Generic, Humans, Pharmacology (medical), Pharmacology, Cross-Over Studies, Therapeutic Equivalency, Area Under Curve, Tablets

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  • citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    1
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Average
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Average
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
1
Average
Average
Average
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