Pharmacokinetics and bioequivalence evaluation of 2 oral formulations of methotrexate tablets in healthy Chinese volunteers under fasting and fed conditions.

Methotrexate is an anti-metabolite drug that is frequently used for rheumatoid arthritis treatment. This study is aimed at evaluating the bioequivalence of 2 methotrexate tablets (2.5 mg) under fasting and fed conditions in healthy Chinese volunteers. A single-center, randomized, open-label, two-drug, two-period, crossover, single-dose trial protocol was designed. Fifty-two healthy Chinese participants were enrolled and randomly classified into fasting (n = 26) and fed (n = 26) group. Fifty of them participated in the whole trial course. Blood samples for pharmacokinetic (PK) analysis were collected 1 h before and up to 24 h after drug administration. To evaluate the bioequivalence of test and reference tablets, PK parameters including maximum plasma drug concentration (Cmax), time to reach maximum concentration (Tmax), area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC0-t), and area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞) were calculated. Our data revealed that 90% CIs of geometric mean ratio of the test or reference drugs for Cmax, AUC0-t, and AUC0-∞ fell within the acceptance range for bioequivalence (80-125%). Besides, it is worthwhile to mention that Cmax and Tmax in the fed group were lower than those in the fasting group. Interestingly, the absorption, measured by AUC, did not have significant difference in both groups. There were no suspected serious adverse reactions or serious adverse events over the entire trial. Our results demonstrated that the test and reference tablets were bioequivalent under fasting and fed conditions.