title: Stereoselective effect of amiodarone on the pharmacokinetics of racemic carvedilol.
abstract: We investigated whether there was a stereoselective effect of amiodarone on the pharmacokinetics of carvedilol. Among a series of 106 inpatients with heart failure, 52 received carvedilol monotherapy (carvedilol group) and 54 received carvedilol plus amiodarone (carvedilol+amiodarone group). The serum carvedilol concentration administered/dose ratio was compared between the two groups based on HPLC measurement of the serum levels of carvedilol, amiodarone, and desethylamiodarone. In 6 patients from the carvedilol group, serum carvedilol levels were compared before and after coadministration of amiodarone. There was no significant between-group difference of the serum concentration to dose (C/D ratio) for the R-enantiomer carvedilol, however, the C/D ratio for the S-enantiomer and the serum S-carvedilol to R-carvedilol (S/R) ratio were both significantly lower in the carvedilol group than in the carvedilol+amiodarone group(47.8+/-56.7 versus 95.3+/-105 ng/mg/kg, P=0.0048 and 0.460+/-0.207 versus 0.879+/-0.377 ng/mg/kg, P<0.001), respectively. Furthermore, the mean S-carvedilol concentration over 14 days of coadministration with amiodarone was higher than that before coadministration (6.54+/-1.73 ng/mL versus 3.03+/-0.670 ng/mL, P<0.001). These results suggest that metabolism of S-carvedilol was markedly inhibited by coadministration of amiodarone.
authors.affiliation: Department of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Fukumoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Komamura
authors.forename: Shiro
authors.initials: S
authors.lastname: Kamakura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ueno
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000638:Amiodarone / Q000494:pharmacology* / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002227:Carbazoles / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077261:Carvedilol; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013237:Stereoisomerism
chemical_list: D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D000638:Amiodarone