Alpha lipoic acid bioequivalence study redesigned: a candidate for highly variable drugs

Authors : Burcu BULUT, Nagehan SARRAÇOĞLU, Onur PINARBAŞLI
Pages : 8-15
View : 41 | Download : 6
Publication Date : 2021-04-30
Article Type : Research Paper
Abstract :Background and Aims: Alpha lipoic acid 600 mg HR film tablet showed high intra-subject variabilities in bioequivalence studies. In this regard, this study aims to determine whether Alpha lipoic acid 600 mg HR film coated tablet is a highly variable drug. Methods: First, a randomized, open-label, balanced, two-treatment, two-period, two-sequence, single-dose, two-way crossover oral bioequivalence study comparing the test product insert ignore into journalissuearticles values(Alpha lipoic acid HR film tablet - ILKO Pharmaceuticals, Turkey); with the reference product insert ignore into journalissuearticles values(Thioctacid®- Meda Pharma, Germany); was conducted in normal, healthy, adult human subjects under fasting conditions insert ignore into journalissuearticles values(Study 1);. Secondly, a randomized, open-label, balanced, two-treatment, four-period, two-sequence, single-dose, fully replicate crossover oral bioequivalence study was conducted in normal, healthy, adult human subjects under fasting conditions insert ignore into journalissuearticles values(Study 2);. Results: Study 1 failed. It had a 90% confidence interval for LnCmax insert ignore into journalissuearticles values(ng/mL); value between 79.69% – 138.98% with a high intra-subject coefficient of variability insert ignore into journalissuearticles values(ISCV=57.5%);. In study 2 a 90% confidence interval for LnCmax insert ignore into journalissuearticles values(ng/mL); was found between 88.40% – 129.81% while the ISCV value for LnCmax was 64.5%. Conclusion: The findings suggest that bioequivalence study for Alpha lipoic acid HR film tablet should be redesigned since this is a highly variable drug. Therefore, conventional bioequivalence acceptable limits insert ignore into journalissuearticles values(80.0%-125.0%); should be adjusted to 69.84% – 143.19% for alpha lipoic acid.
Keywords : Alpha lipoic acid, bioequivalence, highly variable drugs, intra subject variability, replicate design

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