Drug design, development and therapy · 2025
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.
СтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Zhang Peiwen, Li Mupeng, Jiang Hao, Liu Fangfang, Huang Qian, Han Yangyun, Fan Lianlian
Аннотация
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 (Cmax, AUC0-48, and AUC0-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 Cmax, AUC0-48, and AUC0-inf all fell within 80.00%-125.00%, meeting ABE criteria. In the fed cohort, GMRs for Cmax and AUC0-inf were 119.74% and 99.87%, respectively, within RSABE acceptance limits. Food intake delayed drug absorption, resulting in a notable lag time (median Tmax 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.
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 (Cmax, AUC0-48, and AUC0-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 Cmax, AUC0-48, and AUC0-inf all fell within 80.00%-125.00%, meeting ABE criteria. In the fed cohort, GMRs for Cmax and AUC0-inf were 119.74% and 99.87%, respectively, within RSABE acceptance limits. Food intake delayed drug absorption, resulting in a notable lag time (median Tmax 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.