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 microM; 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.