Comparative Studies of Quality and Bioavailability of Methotrexate in Thai Patients with Rheumatoid Arthritis
MALEEYA MANOROT,M.D.*, WORA WIT LOUTHRENOO, M.D.**, SUPANIMIT TEEKACHUNHATEAN, M.D.* NOPPAMAS ROJANASATHIEN, M.D.*, WITTAYA TONSUWANNONT, M.D., Ph.D.***,
Affiliation : * Department of Pharmacology, ** Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. *** Department of Pharmacology, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand.
Abstract The bioavailability of the two generic methotrexate oral preparations (Emtrexate®, Pharma- chemie Company, Hollland and Methotrexate Remedica®, Remedica, Cyprus as the test pre- parations), were compared to the innovator (Methotrexate LederJe®, 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 I 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 LederJe® and Methotrexate Remedica®/ Metho- trexate Lederle® of the Cmax , AUC0-8• and AUCo-a 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 T max difference between Emtrexate®-Methotrexate Lederle® and Methotrexate Remedica®- Methotrexate Lederle® also overlapped the stipulated bioequivalence range of the T max 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.
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