Objective: To compare the bioequivalence of a generic methotrexate (MTX) tablet (Mylan) with that of a brand-name (Lederle) product.
Design: A single-dose, randomized, crossover study.
Setting: Clinical Research Center (CRC) at a university hospital.
Patients: Men and women who had a diagnosis of malignancy or psoriasis who were at least 21 years old.
Methodology: Two overnight study periods were scheduled at the CRC at least one week, but not more than two weeks apart. Each period consisted of a 10-hour fast prior to and 4 hours following oral MTX 15 mg administered as six 2.5-mg tablets. Blood samples were collected over 48 hours. Plasma MTX concentrations were determined using an HPLC assay. Area under the curve from zero to infinity (AUC0-infinity) was calculated by the log-trapezoidal method.
Results: Twenty-two patients (21 psoriasis, 1 colon cancer) aged 23-61 years completed both study periods. Mean values for peak concentration, time to peak concentration, and AUC0-infinity were 0.80 mumol/L, 1.2 hours, and 3.0 mumol.h/L, respectively, for Mylan's MTX tablets and 0.81 mumol/L, 1.4 hours, 3.0 mumol.h/L, respectively, for Lederle's MTX. Normalization for weight or body surface area did not affect interpatient variability. Relative bioavailability of generic MTX was 99.2 percent. Rate and extent of absorption were not significantly different and the confidence intervals were within the range of 80-120 percent required by the Food and Drug Administration.
Conclusions: Mylan's MTX tablet is bioequivalent to Lederle's product.