Metabolism of amiodarone: II. High-performance liquid chromatographic assay for mono-N-desethylamiodarone hydroxylation in liver microsomes

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.