Effects of omeprazole or cola beverage on the pharmacokinetics of oral DA-8159, a new erectogenic, in rats.
The changes in pharmacokinetics of DA-8159 by omeprazole with respect to inhibition of CYP3A1/2 in rats were evaluated. After oral administration of DA-8159 at dose of 30 mg/kg to rats pretreated with oral omeprazole at 30 mg/kg for 1 week, the total area under the plasma concentration-time curve from time zero to time infinity (AUC) of DA-8159 was significantly greater (37.5% increase) than that in control rats. This could be due to inhibition of metabolism of DA-8159 by inhibition of CYP3A1/2 by omeprazole. The AUC(DA-8164 (a metabolite of DA-8159))/AUC(DA-8159) ratio was also smaller (32.4% decrease) with omeprazole. After oral administration of DA-8159 at a dose of 30 mg/kg to rats without or with cola beverage, the pharmacokinetic parameters of DA-8159 and DA-8164 were not significantly different between two groups of rats. This suggested that cola beverage did not have any considerable effects on CYP3A1/2 in rats.
Lee
Joo H
JH
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Republic of Korea.
Bae
Soo K
SK
Kwon
Jong W
JW
Kim
Won B
WB
Lee
Myung G
MG
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors; D001628:Beverages; D030221:Cola; D051544:Cytochrome P-450 CYP3A; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D008657:Metabolic Clearance Rate; D009853:Omeprazole / Q000494:pharmacology*; D010410:Penile Erection / Q000187:drug effects; D011743:Pyrimidines / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides; D000096926:Benzenesulfonamides
D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D009853:Omeprazole; D011743:Pyrimidines; D013449:Sulfonamides; C465260:Cyp3a2 protein, rat; C465138:Cyp3a23-3a1 protein, rat; C419664:udenafil; D000096926:Benzenesulfonamides