Reduced prehepatic extraction of nicardipine in the presence of pioglitazone in rats.
This study investigated the effect of pioglitazone on the pharmacokinetics of oral and i.v. nicardipine in rats. Pharmacokinetic parameters were determined after nicardipine was administered orally (12 mg kg(-1)) or i.v. (4 mg kg(-1)) with or without a single dose of oral pioglitazone (0.3 or 1.0 mg kg(-1)). Compared with the control group given nicardipine alone, coadministration of pioglitazone significantly decreased the total plasma clearance of orally administered nicardipine (by 40.4-46.3%, P < 0.05) and significantly increased the area under the plasma concentration-time curve (by 81.8-96.3%) and the peak plasma concentration, C(max) (by 56.5-66.8%). T(max) and the terminal plasma half-life of nicardipine were not affected, however. Coadministration of oral pioglitazone did not affect the pharmacokinetics of i.v. nicardipine, implying that pioglitazone may mainly decrease the prehepatic extraction of nicardipine during intestinal absorption. In conclusion, pioglitazone significantly enhanced the oral bioavailability of nicardipine in rats by reducing its presystemic clearance.
Choi
Jun-Shik
JS
BK21 project team, College of Pharmacy, Chosun University, 375 Seosuk-dong, Dong-Gu, Gwangju, Korea.
Koh
Young-Youp
YY
Chung
Joong-Hwa
JH
Choi
Dong-Hyun
DH
Han
Hyo-Kyung
HK
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006207:Half-Life; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D007275:Injections, Intravenous; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009529:Nicardipine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D009529:Nicardipine; D000077205:Pioglitazone