Influence of nicardipine and nifedipine on plasma carvedilol disposition after oral administration in rats

• Published in: Journal of pharmacy and pharmacology Vol. 54; no. 6; p. 821
• Main Authors: Hokama, Nobuo, Hobara, Norio, Sakai, Masayuki, Kameya, Hiromasa, Ohshiro, Susumu, Sakanashi, Matao
• Format: Journal Article
• Language: English
• Published: England 01.06.2002
• Subjects: Administration, Oral; Animals; Area Under Curve; Calcium Channel Blockers - administration & dosage; Calcium Channel Blockers - pharmacology; Carbazoles - blood; Carbazoles - pharmacokinetics; Carvedilol; Chromatography, High Pressure Liquid; Drug Interactions; Male; Nicardipine - administration & dosage; Nicardipine - pharmacology; Nifedipine - administration & dosage; Nifedipine - pharmacology; Propanolamines - blood; Propanolamines - pharmacokinetics; Rats; Rats, Sprague-Dawley; Time Factors
• ISSN: 0022-3573
• DOI: 10.1211/0022357021778998

The effect of two kinds of 1,4-dihydropyridine calcium-channel blockers, nicardipine hydrochloride and nifedipine, on the disposition of carvedilol, was studied in rats. Blood samples were assayed for carvedilol levels using solid-phase extraction and high-performance liquid chromatography. The plasma carvedilol concentration was found to be significantly higher, and the area under the concentration-time curve up to 24 h (AUC0-->24) was 6.7 and 3.0 times higher after simultaneous oral administration of 20 mg kg(-1) carvedilol with 40 mg kg(-1) nicardipine hydrochloride, or with 40 mg kg(-1) nifedipine, respectively, than after administration of carvedilol alone. The pharmacokinetic interaction between carvedilol and dihydropyridine calcium-channel blockers is thought to be attributable to vasodilator-induced changes in hepatic first-pass metabolism, inhibition in the absorption barrier by P-glycoprotein and in the metabolism of carvedilol.