Optimization of contraceptive dosage regimen of Centchroman

Centchroman (Ormeloxifene), a non-steroidal oral contraceptive, is used at a dose of 30 mg once a week. To prevent failures in the beginning of the th erapy, it is recommended that a dose of 30 mg twice a week for 12 weeks be administered to build up adequate blood levels. The present study was under taken to simplify the dosing schedule without sacrificing the purpose of tw ice a week dosing regimen, using modeling and measurement approaches. The d rug was given to 60 female volunteers who were divided into seven groups: g roup I, 30 mg weekly; group II, 30 mg twice a week; group III, 30 mg twice a week for 12 weeks followed by 30 mg weekly; group IV, 30 mg twice a week for 6 weeks followed by 30 mg weekly; group V, 60 mg weekly; and groups VI and VII, single 60 mg loading dose followed by 30 mg weekly doses. The bloo d samples were collected and analyzed by HPLC. In group I, mean trough conc entrations of centchroman and its active metabolite, 7-desmethyl centchroma n, were comparable to the steady-state trough concentrations in groups III, IV, VI, and VII. The metabolite to parent drug ratio remained constant in all the groups. The pharmacokinetic parameters in group VII were comparable to those reported after a single 30 mg dose. Dosage regimen VI was more co nvenient and provided better pregnancy protection (Pearl index 1.18; unpubl ished report) than regimen III, which is currently on the market and, thus, could be effectively used for contraception. (C) 2001 Elsevier Science Inc . All rights reserved.