Pharmacokinetic Interaction of Tetracycline with Centchroman in Healthy Female Volunteers
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ORIGINAL RESEARCH ARTICLE
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Pharmacokinetic Interaction of Tetracycline with Centchroman in Healthy Female Volunteers Manoj Khurana,1 Jawahar Lal,1 Ved P. Kamboj,2 Swaran Nityanand3 and Ram C. Gupta1 1 2 3
Pharmacokinetics and Metabolism Division, Central Drug Research Institute, Lucknow, India Endocrinology Division, Central Drug Research Institute, Lucknow, India Clinical and Experimental Medicine Division, Central Drug Research Institute, Lucknow, India
Abstract
Objective: We aimed to investigate the effect of tetracycline coadministration, with and without lactic acid bacillus spores supplementation, on the pharmacokinetics of centchroman, a nonsteroidal oral contraceptive, in healthy female volunteers. Participants and methods: The study was a single-centre, single-blinded, randomised, parallel treatment study in healthy female subjects of reproductive age randomised to two groups (11 subjects in each group). On day 1, subjects were given either a single oral dose of centchroman 30mg with tetracycline 250mg (group A) or a single dose of centchroman 30mg, tetracycline 250mg and one tablet containing 60 million lactic acid bacillus spores (group B). Tetracycline (250mg three times daily) and lactic acid bacillus spores (one tablet three times daily) were continued for 3 days. Serial blood samples were collected and analysed by high performance liquid chromatography. The pharmacokinetic parameters were compared with the control data reported previously from this laboratory. Results: Coadministration of tetracycline yielded significantly higher maximum plasma concentrations (Cmax) [35%] and a shorter time to reach Cmax (tmax) values for centchroman (42%) than those obtained in the control group of females (p < 0.05). Inclusion of lactic acid bacillus spores in the regimen resulted in similar effects with increased Cmax (47%) and area under the concentration-time curve from time zero to infinity (34%) of centchroman (p < 0.05) with a significant decrease in tmax. Other parameters such as half-life, apparent clearance, apparent volume of distribution and mean residence time of centchroman were not affected by either of the treatments. Conclusions: The apparent effects of either of the regimens on centchroman pharmacokinetics seem to be of little clinical relevance in terms of increased rate or extent of availability. It can be concluded that this tetracycline-containing regimen is unlikely to alter the contraceptive efficacy of centchroman in humans.
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Centchroman (ormeloxifene), is a nonsteroidal, selective estrogen receptor modulator and once-weekly oral contraceptive developed at the Central Drug Research Institute, Lucknow, India.[1-4] It is currently marketed in India as an oral contraceptive. Centchroman is undergoing clinical evaluation for the treatment of advanced breast cancer and for prevention of osteoporosis due to its potent antiestrogenic and weak estrogenic activities.[5,6] It provides good pregnancy protection in women post-coitus as well
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