Comparative bioavailability study of single-dose film-coated and sugar-coated ethionamide tablets in healthy volunteers.

Background: Ethionamide sugar-coated tablets have been reformulated to film-coated tablets to improve dissolution and stability.

Objective: The study objective was to compare the bioavailability of the film-coated (test) and sugar-coated (reference) formulations of ethionamide.

Methods: After providing informed consent and undergoing screening procedures, 40 healthy subjects were assigned to receive a single dose of ethionamide 250-mg film- or sugar-coated tablets, in randomized order, in the fasted state. Serial blood samples were collected before and from 0.5 to 24 hours after dosing. After a 7-day washout, procedures were repeated for the other formulation. The blood samples were processed to provide plasma samples, which were frozen until assay. Plasma ethionamide concentrations were measured using a validated LC-MS/MS method, with a lower limit of quantitation of 20 ng/mL. Pharmacokinetic parameters were determined using noncompartmental methods, with subsequent evaluation for bioequivalence.

Results: All 40 subjects (37 men, 3 women; mean age, 28 years; mean weight, 74 kg) completed the study. Seven subjects reported a total of 10 adverse events (5 with each formulation), all of which were mild and considered possibly related to drug treatment. None of the events resulted in discontinuation from the study. Mean (SD) pharmacokinetic properties observed with the film- and sugar-coated tablets, respectively, were as follows: Cmax, 2160 (614) and 1484 (636) ng/mL; Tmax, 1.0 (0.5) and 1.5 (0.9) hours; ke, 0.369 (0.053) and 0.232 (0.114) h(-1); t½, 1.92 (0.27) and 4.06 (2.52) hours; and AUC, 7668 (1688) and 6594 (1764) ng · h/mL.

Conclusions: Comparing AUC values, the formulations were bioequivalent. The maximum concentrations observed with the film-coated product were higher but were more consistent (%CV, 28%) compared with those of the sugar-coated formulation (%CV, 43%).