- 著者
-
Kyoko FUKUMOTO
Takashi KOBAYASHI
Kazuo KOMAMURA
Shiro KAMAKURA
Masafumi KITAKAZE
Kazuyuki UENO
- 出版者
- 日本薬物動態学会 会長/日本薬物動態学会 DMPK編集委員長
- 雑誌
- Drug Metabolism and Pharmacokinetics (ISSN:13474367)
- 巻号頁・発行日
- vol.20, no.6, pp.423-427, 2005 (Released:2006-01-11)
- 参考文献数
- 30
- 被引用文献数
-
13
11
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.