Evaluation of interaction potential of certain concurrently administered drugs with pharmacological and pharmacokinetic profile of centchroman in rats.
Centchroman (Ormeloxifene) is a nonsteroidal, selective estrogen receptor modulator, oral contraceptive and anticancer agent, and is intended for long-term use by women. In view of its vast clinical application and the interaction of steroidal oral contraceptives with certain commonly used therapeutic agents, evaluation of interaction of certain concomitantly administered therapeutic agents (ibuprofen, rifampicin, diazepam, salbutamol, nifedipine, paracetamol, haloperidol, and tetracycline), in terms of both the postcoital contraceptive efficacy and pharmacokinetic profile, with centchroman was undertaken in female Sprague-Dawley rats. Among the representatives from each commonly used therapeutic category, interaction (pharmacokinetic) was observed with ibuprofen (60 mg/kg, twice daily), haloperidol (0.7 mg/kg, twice daily), and tetracycline (140 mg/kg, twice daily) coadministration on Days 1 through 5 postcoitum. Of these three therapeutic agents, only tetracycline interfered with the contraceptive efficacy of centchroman. It reduced the bioavailability of centchroman and its active metabolite by increasing their excretion through bile and feces. Increased metabolite excretion on tetracycline coadministration indicates the enterohepatic recirculation of the metabolite, not the parent drug. However, the effect of tetracycline was negated by the inclusion of lactic acid bacillus spores in the regimen.
Khurana
M
M
Pharmacokinetics and Metabolism Division, Central Drug Research Institute, Lucknow 226001, India.
Lal
J
J
Singh
M M
MM
Paliwal
J K
JK
Kamboj
V P
VP
Gupta
R C
RC
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001646:Bile / Q000378:metabolism; D001682:Biological Availability; D002486:Centchroman / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003283:Contraceptives, Postcoital, Synthetic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005243:Feces / Q000737:chemistry; D005260:Female; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013754:Tetracyclines
D000900:Anti-Bacterial Agents; D003283:Contraceptives, Postcoital, Synthetic; D013754:Tetracyclines; D002486:Centchroman