Effect of ketoconazole on the pharmacokinetics of ornidazole--a possible role of p-glycoprotein and CYP3A.
The influence of ketoconazole, a modulator of P-glycoprotein (P-gp), on the exsorption of ornidazole from everted sacs of rat intestine (duodenum, jejunum and ileum) was investigated. The effect of ketoconazole pretreatment on the pharmacokinetics of ornidazole was also studied in eight healthy human volunteers. After overnight fasting ornidazole 500 mg was administered before and after pretreatment with ketoconazole 200 mg once daily for 7 days. Serum samples were analyzed by reversed phase HPLC. Significant differences were observed in pharmacokinetic parameters C(max), AUC(0-t), AUC(0-infinity), T(max) and clearance. Ornidazole is believed to be metabolized through CYP3A and it has considerable intestinal efflux, which was observed from the in vitro study. The altered pharmacokinetic parameters can be attributed to ornidazole efflux from the blood to the intestine and its metabolism by CYP3A in the intestine.
Ramesh
Srirangam
S
University College of Pharmaceutical Sciences, Kaktiya University, Warangal, India.
Kumar
Yamsani Shravan
YS
Rao
Yamsani Madhusudan
YM
D000328:Adult; D000563:Amebicides / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001682:Biological Availability; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007654:Ketoconazole / Q000494:pharmacology*; D008297:Male; D009950:Ornidazole / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D046509:Tissue Culture Techniques
D000563:Amebicides; D000935:Antifungal Agents; D009950:Ornidazole; D051544:Cytochrome P-450 CYP3A; D007654:Ketoconazole