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.
Ha
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HR
Department of Internal Medicine, University Hospital of Zurich, Switzerland. huyriem.ha@dim.usz.ch
Kozlik
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P
Stieger
B
B
Bigler
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L
Follath
F
F
D000638:Amiodarone / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D006900:Hydroxylation; D008862:Microsomes, Liver / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
D000889:Anti-Arrhythmia Agents; C440780:mono-N-desethylamiodarone; D000638:Amiodarone