IN VITRO EVALUATION OF THE PHARMACOKINETIC ALTERATIONS CAUSED BY SULFAMETHOXAZOLE ON GLIMEPIRIDE HYDROXYLATION: PREDICTION OF THE IN VIVO DRUG DRUG INTERACTION FROM IN VITRO DATA.
Dipti B. Ruikar*, Sadhana J. Rajput
Quality Assurance Laboratory, Centre Of Relevance And Excellence In Novel Drug Delivery System, Pharmacy Department, G. H. Patel Pharmacy Building, Donor’s Plaza, The Maharaja Sayajirao University Of Baroda, Fatehgunj, Vadodara-390 002 Gujarat, India.
The aim of this work was to investigate the effect of inhibition of CYP2C9 on the pharmacokinetics of glimepiride (GLM), with sulfamethoxazole (SMZ) as model inhibitor of CYP2C9 in vitro using human liver microsomes (HLM). The present study investigates and compares the impact of GLM as a substrate and SMZ as inhibitor on invitro kinetic parameters, namely Km, Vmax, IC50 and Ki. Attempts have also been made to quantitatively predict in vivo drug interactions in humans from in vitro data. The results indicate that, SMZ when used at concentrations lower than 500 μMole, can be used as selective inhibitor of CYP2C9 for in vitro studies. In this study, we systematically evaluated the inhibitory effects of SMZ on GLM metabolism mediated by CYP2C9. The predicted increase in plasma concentration of GLM is high, suggesting the risk of hypoglycemia when SMZ is coadministered with GLM.