Metabolism of amiodarone: II. High-performance liquid chromatographic assay for mono-N-desethylamiodarone hydroxylation in liver microsomes |
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| Authors: | Huy Riem Ha Peter Kozlik Bruno Stieger Laurent Bigler Ferenc Follath |
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| Affiliation: | a Cardiovascular Therapy Research Unit, Department of Internal Medicine, University Hospital of Zurich, Ramistrasse 100, 8091 Zurich, Switzerland;b Clinical Pharmacology and Toxicology Division, Department of Internal Medicine, University Hospital of Zurich, Ramistrasse 100, 8091 Zurich, Switzerland;c Institute of Organic Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland |
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| Abstract: | Amiodarone (AMI) is a potent antiarrhythmic drug. In vivo and in vitro, AMI is biotransformed to mono-N-desethylamiodarone (MDEA). Recently, it was observed that MDEA was further hydroxylated to n-3′-hydroxybutyl-MDEA (3′OH-MDEA). The performance of a HPLC–UV assay being developed for the quantification of the new compound was investigated. Liver microsomes isolated from rabbit, rat and human biotransformed MDEA to 3′OH-MDEA. Their estimates of Michaelis–Menten parameters were Km=6.39, 25.2, 19.4 μM; Vmax=560, 54, 17.3 pmol/mg protein/min), respectively. Thus, hydroxylase activity in mammals may be the origin of the species dependence observed in the AMI metabolism. |
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| Keywords: | Amiodarone Mono-N-desethylamiodarone |
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