Comparative studies of quality and bioavailability of methotrexate in Thai patients with rheumatoid arthritis

Abstract

The bioavailability of the two generic methotrexate oral preparations (Emtrexate®, Pharmachemie Company, Hollland and Methotrexate Remedica®, Remedica, Cyprus as the test preparations), were compared to the innovator (Methotrexate Lederle®, Lederle, U.S.A. as the reference) in 10 patients with rheumatoid arthritis. A single 7.5 mg oral dose of each preparation was given to the subjects in a randomized, double-blind, three-period crossover design with a 1 week washout period. Serum methotrexate concentrations were determined by using Fluorescence Polarization Immunoassay (Abbott TDx®). No significant differences in pharmacokinetic parameters (AUC, Cmax, and Tmax) were observed between the test and reference preparations. The mean and 90 per cent CI of the ratio Emtrexate/Methotrexate Lederle® and Methotrexate Remedica®/ Methotrexate Lederle® of the Cmax , AUC0-8, and AUC0-α were 0.93 (0.87-1.00), 0.9 (0.82-0.98), 0.88 (0.79-0.99) and 0.97 (0.93-1.02), 0.95 (0.90-0.99), 0.94 (0.86-1.02), respectively. These values were well within the acceptable bioequivalence range of 0.8-1.25. The mean and 90 per cent CI of Tmax difference between Emtrexate®-Methotrexate Lederle® and Methotrexate Remedica®-Methotrexate Lederle® also overlapped the stipulated bioequivalence range of the Tmax differences of ± 0.25 hour. Thus, Emtrexate® and Methotrexate Remedica® were considered bioequivalent to the reference Methotrexate Lederle® regarding the rate of absorption and the extent of absorption.