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 RESEARCH ARTICLE
Year : 2010  |  Volume : 42  |  Issue : 3  |  Page : 146-149

Effect of centchroman coadministration on the pharmacokinetics of metformin in rats


Pharmacokinetics & Metabolism Division, Central Drug Research Institute, CSIR, Lucknow - 226 001, India

Correspondence Address:
Jawahar Lal
Pharmacokinetics & Metabolism Division, Central Drug Research Institute, CSIR, Lucknow - 226 001
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7613.66836

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Objectives : To study the effect of centchroman, a non-steroidal oral contraceptive, coadministration on the pharmacokinetics of metformin in rats. Materials and Methods : The pharmacokinetic interaction of metformin was studied in normal Sprague-Dawley female rats with and without centchroman coadministration. Blood samples were analyzed using a validated high-performance liquid chromatography method to generate the pharmacokinetic profile of metformin. The C max and t max were directly read from the concentration-time data. Other pharmacokinetic parameters were estimated using non-compartmental analyses. Results : Metformin was monitored up to 10 h, and it exhibited a double-peak phenomenon. The C max 1, 2.62 ± 0.32 μg/ml, and C max 2, 2.96 ± 0.65 μg/ml, occurred after 0.75 and 3 h post-dose, respectively. The mean residence time (MRT), AUC 0-4 h and volume of distribution (Vd/F) were 4.20 ± 0.30 h, 8.53 ± 1.89 μg.h/ml and 14.24 ± 5.42 L/kg, respectively. Following centchroman coadministration, metformin showed significantly (P < 0.05) higher C max (C max 1, 3.96 ± 0.55 μg/ml and C max 2, 5.21 ± 0.59 μg/ml), AUC 0-4 h (12.28 ± 0.73 μg.h/ml) and Vd/F (18.29 ± 1.19 L/kg), but lower MRT (3.19 ± 0.36 h) than the values obtained after metformin dosing alone. However, AUC0-t (17.74 ± 5.58 μg.h/ml) and clearance (3.76 ± 0.80 L/h/kg) remained unchanged. Conclusions : The results indicate that centchroman coadministration increases the rate but not the extent of absorption of metformin in rats. However, it does not seem to alter the pharmacokinetics of metformin to clinically significant levels.






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