Influence of nicardipine and nifedipine on plasma carvedilol disposition after oral administration in rats.
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.
Hokama
Nobuo
N
Department of Hospital Pharmacy, School of Medicine, Faculty of Medicine, University of the Ryukyus, Aza Uehara, Okinawa, Japan.
Hobara
Norio
N
Sakai
Masayuki
M
Kameya
Hiromasa
H
Ohshiro
Susumu
S
Sakanashi
Matao
M
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002227:Carbazoles / Q000097:blood / Q000493:pharmacokinetics*; D000077261:Carvedilol; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D008297:Male; D009529:Nicardipine / Q000008:administration & dosage / Q000494:pharmacology*; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology*; D011412:Propanolamines / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002121:Calcium Channel Blockers; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D009529:Nicardipine; D009543:Nifedipine