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 therapy, 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 undertaken to simplify the dosing schedule without sacrificing the purpose of twice a week dosing regimen, using modeling and measurement approaches. The drug was given to 60 female volunteers who were divided into seven groups: group 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 blood samples were collected and analyzed by HPLC. In group I, mean trough concentrations of centchroman and its active metabolite, 7-desmethyl centchroman, 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 Dosage regimen VI was more convenient and provided better pregnancy protection (Pearl index 1.18; unpublished report) than regimen III, which is currently on the market and, thus, could be effectively used for contraception.