title: Influence of nicardipine and nifedipine on plasma carvedilol disposition after oral administration in rats.
abstract: 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.
authors.affiliation: Department of Hospital Pharmacy, School of Medicine, Faculty of Medicine, University of the Ryukyus, Aza Uehara, Okinawa, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Hokama
authors.forename: Norio
authors.initials: N
authors.lastname: Hobara
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sakai
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Kameya
authors.forename: Susumu
authors.initials: S
authors.lastname: Ohshiro
authors.forename: Matao
authors.initials: M
authors.lastname: Sakanashi
mesh_terms: 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
chemical_list: D002121:Calcium Channel Blockers; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D009529:Nicardipine; D009543:Nifedipine