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Pharmacokinetics and safety of the antitumor drug everolimus in healthy Chinese subjects: a single-dose, open-label, randomized, two-sequence, two-period crossover, phase I bioequivalence study

Year: 2025

Type: article

Abstract: Purpose It aims to evaluate the pharmacokinetic (PK) similarity and safety of everolimus in whole blood under fasting and postprandial conditions and its generics in Chinese healthy subjects. Methods Healthy subjects were enrolled in a single-dose, open-label, randomized, two-sequence, two-period crossover study (Clinical trial registry number: CTR20220446) under fasting and postprandial conditions. The blood concentration of everolimus was quantified by a validated and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Results All 90% CIs for the geometric mean ratios of C max , AUC 0-t , and AU C 0 − ∞ were within the bioequivalence range of 80.00%–125.00%. the maximum intra-individual CV% of variation were 22.76% and 18.63% under fasting and fed conditions, respectively. The gastrointestinal absorption rate was decreased by food intake: median T max was 0.75 h in the fasted state, and 3.00 h after a high-fat meal. The average elimination half-life (t 1/2β , 37.19–38.43 h) and mean residence time (MRT, 23.13–25.81 h) did not appear to be affected by food intake regardless of fasting or fed state. In this study, no serious AE (SAEs) were observed throughout the trial. Conclusion The systemic availability of a single oral 5 mg dose of everolimus is significantly reduced by coadministration with fed compared with fasting conditions, the test formulation ( T ) and the reference formulation ( R ) were bioequivalent. Clinical Trial Registration clinicaltrials.gov , identifier CTR20220446, ( http://www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml ).

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2025.1718032