Evidence map›Paper›PMID 40000474›Full record

ArticleEuropean journal of clinical pharmacology2025

Considerations of sex in bioequivalence assessments: does sex affect pharmacokinetic variability between evaluation formulations?

Ji-Hun Jang, Seung-Hyun Jeong

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Article in European journal of clinical pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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2 authors.

Ji-Hun JangCollege of Pharmacy, Chonnam National University, 77 Yongbong-Ro, Buk-Gu, Gwangju, 61186, Republic of Korea.
Seung-Hyun JeongCollege of Pharmacy, Sunchon National University, 255 Jungang-Ro Jeollanam-Do, Suncheon-Si, 57922, Republic of Korea. jeongsh@scnu.ac.kr.

Funding

National Research Foundation of Korea RS-2023-00245453
6 · The paper itself

Abstract

backgroundBioequivalence assessment determines the equivalence between drug formulations and is primarily used to demonstrate that a generic product is equivalent to its reference. The sex of the drug consumer is a major consideration in bioequivalence assessment, but specific ratios or absolute criteria for sex composition are usually not specified. PURPOSE: This study explored whether the sex of participants in a bioequivalence assessment could significantly affect the pharmacokinetic variability between formulations and decision outcomes. In bioequivalence studies, the sex composition should reflect the drug's target population, but it is often acceptable to limit it to healthy adult males. Therefore, it is essential to consider the variation in bioequivalence results according to sex.

methodsLevocetirizine and rabeprazole enteric-coated tablets were chosen as investigational agents, and clinical trial data for these were used in the bioequivalence analysis. This analysis was conducted both with and without considering sex, and the final determination of equivalence was based on whether the 90% confidence interval for the ratio of standard pharmacokinetic parameters between the reference and test formulations fell within the 80 to 125% range. Additionally, principal component analysis (PCA) was performed to determine whether there were significant differences in the targeted pharmacokinetic parameter values between drug formulations across each sex group.

resultsBioequivalence of levocetirizine's reference and test formulations was confirmed, independent of sex. For rabeprazole, bioequivalence was established in males-even without considering sex-but not in females, based on extended criteria for drugs with significant pharmacokinetic variability. The PCA results also showed that there were significant differences (P < 0.05) in the distribution of pharmacokinetic parameters of rabeprazole by gender and formulation. This indicates that equivalence assessments may vary based on pharmacokinetic differences related to sex among subjects in bioequivalence studies. Thus, it was shown that sex may influence pharmacokinetic variability between reference and test formulations of the same drug.

conclusionThis study provided valuable insights into the role of sex in bioequivalence studies. For drugs exhibiting significant pharmacokinetic differences between sexes, it is crucial to recognize that bioequivalence results may vary based on the sex ratio in the participant group. Therefore, further analysis and interpretation, taking sex-related factors into account, will be necessary during bioequivalence evaluations.

Indexed as

CetirizineRabeprazoleAdultFemaleHumansMaleMiddle AgedSex FactorsTabletsTherapeutic EquivalencyYoung AdultCetirizineRabeprazoleTabletsBioequivalence assessmentsFormulationsPharmacokinetic variabilitySex

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.