Bioequivalue of two mycophenolate sodium enteric-coated tablets and the drug monitoring based on limited sampling strategy: A single-center, randomized, open-label, three-period, reference-replicated, crossover study

• Published in: Transplant immunology Vol. 81; p. 101923
• Main Authors: Xu, Guangxun, Wang, Zhendi, Yan, Tianzhong, Li, Jinyu, Zhou, Xiaofeng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2023
• Subjects: Allergy and Immunology; Bioequivalence; Limited sampling strategy; Mycophenolate sodium enteric-coated tablet; Pharmacokinetics; Safety; Mycophenolate sodium enteric-coated tablet; Safety; Bioequivalence; Pharmacokinetics; Limited sampling strategy
• ISSN: 0966-3274; 1878-5492; 1878-5492
• DOI: 10.1016/j.trim.2023.101923

A mycophenolate sodium enteric-coated tablet has shown a satisfying anti-rejection effect in patients receiving solid organ transplantation. The current study evaluated the bioequivalence between the test (Ruiyirong®) vs. reference (Myfortic®) formulations by exploring equations for predicting their area under the concentration-time curve (AUC) using a limited sampling strategy in healthy subjects. Forty-eight healthy Chinese subjects were randomized into three administration sequences (test-reference-reference, reference-reference-test, and reference-test-reference) to receive the Ruiyirong or Myfortic treatment on days 1, 8, and 15. The 90% confidential interval (CI) of the geometric mean ratios (test/reference) of maximum plasma concentration (Cmax), the AUC from time 0 to the last timepoint (AUC0–t), and the AUC from 0 to infinity (AUC0–∞) was 92.90%–110.57%, 96.91%- 101.80%, and 96.71%–101.84%, respectively. All these values fell into the bioequivalence criteria of 80.00%–125.00% (based on the criteria of the Food and Drug Administration). The adverse events were 10.4% in Ruiyirong test group and 14.6% in Myfortic reference group. Eight equations for estimating the AUC of the Ruiyirong test and Myfortic reference formulations were evaluated; most of them worked well with the R-value >0.8. Among the four chosen equations, the intragroup verification exhibited a high agreement with the R-value ranging from 0.857 to 0.971 and with the low predictive error (PE > 5% with absolute PE > 15%). Meanwhile, the intergroup verification indicated a high inter-agreement with the R-value ranging from 0.896 to 0.974 (all P < 0.001). The Ruiyirong test vs. Myfortic reference formulations meet the bioequivalent criteria and are well tolerated. The further linear regression analysis explores eight equations predicting the AUC value and the chosen four equations for the Ruiyirong test and Mayfortic reference formulations are interchangeable. •This is a randomized, three-period, reference-replicated, crossover study.•Generic and branded mycophenolate sodium enteric-coated tablets are bioequivalent.•Safety profile is not different between generic and branded products.•Area under curve prediction equations with 2–5 sample points show high performance.•The prediction equations of generic and branded products are interchangea.