Negligible pharmacokinetic interaction between oral DA-8159, a new erectogenic, and amlodipine in rats.
A pharmacokinetic interaction between oral DA-8159 and amlodipine was evaluated in male Sprague-Dawley rats. In rats pretreated with troleandomycin (a main inhibitor of CYP3A1/2 in rats), the AUC(0-6 h) of amlodipine was significantly greater than the controls (34.5+/-6.01 compared with 28.0+/-4.70 microg min/ml), indicating that amlodipine is metabolized via CYP3A1/2 in rats. It was reported that the metabolism of DA-8159 and the formation of DA-8164 (a metabolite of DA-8159) were mainly mediated via CYP3A1/2 in rats, and amlodipine significantly inhibited the CYP3A2 in rats. Therefore, a pharmacokinetic interaction between the two drugs could be expected. However, after oral administration of DA-8159 at a dose of 30 mg/kg with or without oral amlodipine at a dose of 5 mg/kg to rats, the pharmacokinetic parameters of DA-8159 and DA-8164 were not significantly different between the two groups of rats. Similar results were also obtained from amlodipine between with and without DA-8159. The above data indicated that the pharmacokinetic interaction between oral DA-8159 and amlodipine was almost negligible in rats.
Lee
Joo H
JH
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Kim
Eun J
EJ
Kwon
Jong W
JW
Yoo
Moohi
M
Lee
Myung G
MG
D000284:Administration, Oral; D017311:Amlodipine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D005243:Feces / Q000737:chemistry; D041981:Gastrointestinal Tract / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides; D013997:Time Factors; D014217:Troleandomycin / Q000008:administration & dosage / Q000493:pharmacokinetics; D014443:Tyrosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000096926:Benzenesulfonamides
D017311:Amlodipine; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D014217:Troleandomycin; D014443:Tyrosine; C502127:DA-8164; C465138:Cyp3a23-3a1 protein, rat; C419664:udenafil; D000096926:Benzenesulfonamides; C031173:tiropramide