Pharmacokinetics and The Bioequivalence of Oral Methimazole in Healthy Thai Volunteers, Determined By The Sensitive Analytical Method, Lc-Ms/Ms
The pharmacokinetic parameters and bioequivalence of test and reference methimazole products were determined. A randomized, open-label, single-dose, two-treatment, two-period, two-sequence, crossover design between the administration of 5 mg methimazole tablets with a one-week wash-out period was conducted on 22 healthy Thai volunteers. Each volunteer was assigned to receive a single dose of the test or reference product. At 0.0, 10, 20, 30 and 45 min, and then 1, 1.33, 1.67, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0 and 48.0 h after ingesting the pharmaceutical product, blood samples were collected. The plasma methimazole concentrations were analyzed by the validated LC-MS/MS. The Cmax, Tmax, T1/2, AUC0-48h, and AUC0-inf parameters were determined, and 90% confidence intervals were calculated based on the log-transformed data. The mean Cmax, AUC0-48h, AUC0-inf and T1/2 were 157.79 and 163.16 ng/ml, 1058.55 and 1040.52 ng.h/ml, 1160.16 and 1123.15 ng. h./ml and 6.29 and 6.01 h for the test and reference formulations, respectively. The mean ratios for the log-transformed data were -0.0261, 0.0234 and 0.0402 for Cmax, and AUC0-48h and AUC0-inf, respectively. In terms of the rate and extent of the absorption, the test and reference methimazole 5 mg tablets were bioequivalent.
Index Terms—Bioequivalence, LC-MS/MS, Methimazole, Pharmacokinetic,