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Pharmacokinetics and Bioequivalence of Mycophenolate Sodium Enteric-Coated Tablets Under Fasting and Fed Conditions: A Single-Dose, Open-Label, Four-Period Replicated Crossover Study in Healthy Chinese Male Subjects

Year: 2025

Type: article

Abstract: Aim: Enteric-coated mycophenolate sodium (EC-MPS) is an immunosuppressant used to prevent organ rejection in kidney transplant patients. This study assesses the pharmacokinetics and bioequivalence of a generic EC-MPS formulation (180 mg) relative to the branded product (Myfortic ® ), and investigates the effect of food on its pharmacokinetic behavior. Methods: A single-dose, open-label, four-period replicated crossover study with a 7-day washout was conducted in 60 healthy Chinese male subjects under fasting and fed conditions. Eligible subjects were enrolled in two independent trials (fasting and fed conditions) and randomized 1:1 into two treatment sequence groups, with 15 subjects per group. In each group, subjects received a single 180 mg oral dose of the generic or branded product after a 10-hours overnight fast. Plasma concentrations of mycophenolic acid were quantified using a validated LC-MS/MS method. Primary pharmacokinetic parameters (C max , AUC 0-48 , and AUC 0-inf ) were evaluated via a non-compartmental model and analyzed by analysis of variance. Bioequivalence was determined using reference-scaled average bioequivalence (RSABE) for highly variable parameters (CV ≥ 30%) and average bioequivalence (ABE) otherwise, with 90% confidence intervals (CIs) within 80.00%-125.00%. Results: All subjects completed the study. Bioequivalence was established between the generic and branded formulations under both fasting and fed conditions. In the fasting cohort, 90% CIs for the geometric mean ratios (GMRs) of C max , AUC 0-48 , and AUC 0-inf all fell within 80.00%-125.00%, meeting ABE criteria. In the fed cohort, GMRs for C max and AUC 0-inf were 119.74% and 99.87%, respectively, within RSABE acceptance limits. Food intake delayed drug absorption, resulting in a notable lag time (median T max 7.0 h vs 2.5– 3.0 h, p< 0.01) and increased inter- and intra-individual variability. Twenty mild adverse events (AEs) were reported; no serious AEs occurred. Conclusion: The generic EC-MPS demonstrated bioequivalence to the branded product under all tested conditions, supporting its clinical interchangeability. Both formulations were well tolerated in healthy Chinese males. Clinical Trial Registration: http://www.chictr.org.cn/ , Registration No: ChiCTR2300075403. Plain Language Summary: Why was the study done? This study compared a generic enteric-coated mycophenolate sodium (EC-MPS) tablet to the branded product to confirm bioequivalence and evaluate how food affected drug absorption in healthy Chinese males. What did the researchers do and find? A carefully designed study where 60 healthy Chinese male participants took the drug at different times, both with and without food. Blood tests confirmed bioequivalence between the generic and branded tablets. Food delayed the time to peak drug levels and increased variability in pharmacokinetic parameters. Mild side effects occurred but were not severe. What do these results mean? The generic EC-MPS is a safe, effective alternative to the branded product. However, food delays drug absorption, highlighting the need for fasting administration to ensure consistent drug levels. Clinicians should monitor patients closely, especially those taking EC-MPS with meals. These findings are based on healthy male participants in China, and need further verification in female groups and transplant patients. Keywords: pharmacokinetics, bioequivalence, enteric-coated mycophenolate sodium, four-period, food effect

Source: Drug Design Development and Therapy

DOI: 10.2147/dddt.s529915