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

Sep 28, 2026

Purpose: Evaluate pharmacokinetic (PK) similarity and safety of everolimus in whole blood under fasting versus postprandial conditions, and assess bioequivalence of a generic versus reference formulation in Chinese healthy subjects. Methods: Conducted a single-dose, open-label, randomized, two-sequence, two-period crossover study (CTR20220446) with fasting and fed arms, measuring everolimus concentrations using validated LC-MS/MS. Results: 90% CIs for geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ stayed within 80.00%–125.00%; Tmax decreased with food, and no serious adverse events occurred. Conclusion: Fed state reduced systemic availability of a 5 mg dose, while test and reference formulations were bioequivalent.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Introduction

Everolimus background and prior evidence

Purpose

Methods

Study design and analytical method

Results

Bioequivalence outcomes and food effects

Safety findings

Conclusion

Clinical trial registration

TYPE Clinical Trial PUBLISHED 18 December 2025 DOI 10.3389/fphar.2025.1718032 OPEN ACCESS EDITED BY Khosrow Kashﬁ, City University of New York, United States REVIEWED BY Ping Du, Capital Medical University, China Cody J. Peer, Amgen, United States *CORRESPONDENCE Hong Zhang, [ZLhospital@163.com](ZLhospital@163.com) RECEIVED 03 October 2025 REVISED 29 November 2025 ACCEPTED 08 December 2025 PUBLISHED 18 December 2025 CITATION Chen X, Yi X, Liu Y, Wang X, Peng Y, Wang Q, Shuai Y and Zhang H (2025) Pharmacokineticsand safety of the antitumor drug everolimus in healthy Chinese subjects: a single-dose, openlabel, randomized, two-sequence, two-period crossover, phase I bioequivalence study. Front. Pharmacol. 16:1718032 . doi: 10.3389/fphar.2025.1718032 COPYRIGHT © 2025 Chen, Yi, Liu, Wang, Peng, Wang, Shuai and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Pharmacokinetics and safety of the antitumor drug everolimus in healthy Chinese subjects: a single-dose, open-label, randomized, two-sequence, two-period crossover, phase Ibioequivalence study Xiaodan Chen 1, Xiaoyi Yi 1, Yuting Liu 1, Xiaosong Wang 1, Yahui Peng 1, Qiong Wang 1, Ying Shuai 1 and Hong Zhang 􀀁 1,2* 1Clinical Medicine Research Center, Jiangxi Cancer Hospital & Institute (The Second Afﬁliated Hospital of Nanchang Medical College), Nanchang, China, 2Jiangxi Key Laboratory of Translational Research for Cancer, Jiangxi Clinical Research Center for Cancer, Nanchang, China 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 Cmax, AUC0-t, and AUC0−∞ were within the bioequivalence range of 80 . 00%–125 . 00% . the maximum intraindividual 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 Tmax was 0 .75 h in the fasted state, and 3 . 00 h after a high-fat meal. The average elimination half-life (t1/2β, 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](clinicaltrials.gov), identiﬁer CTR20220446, ([http://](http://)[ ](http://)[www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml](www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml)) . KEYWORDS bioequivalence, everolimus, healthy subject, pharmacokinetics, the antitumor drug Frontiers in Pharmacology 01 [frontiersin.org](frontiersin.org) 1 Introduction Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, achieves triple anti-tumor effects by blocking the PI3KAKT-mTOR signaling pathway: inhibiting tumor cell growth, reducing tumor ce

FAQs

What is the purpose of this everolimus phase I study in healthy Chinese subjects?

The study evaluates PK similarity and safety under fasting and postprandial conditions and compares bioequivalence between a test formulation and a reference formulation.

How was everolimus pharmacokinetics measured, and what study design was used?

Healthy subjects received single-dose everolimus in a randomized, open-label, two-sequence, two-period crossover design. Blood everolimus concentrations were quantified using validated LC-MS/MS.

What effect did food have on everolimus exposure, and were test and reference formulations bioequivalent?

Food intake decreased exposure, reflected by a later Tmax after a high-fat meal. The 90% confidence intervals for Cmax, AUC0-t, and AUC0-∞ geometric mean ratios were within 80.00%–125.00%, supporting bioequivalence.

Sep 28, 2026

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