The present work was designed to determine whether the individual differences in pharmacokinetics and pharmacodynamics of amiodarone and its N-desethyl metabolite are related to cytochrome CYP3A metabolizer status. Methods: 12 cardiac patients with inducible ventricular tachyarrhythmias during the baseline electrophysiologic study were enrolled in this study. Urinary 24-hour excretion of 6β-hydroxycortisol (6β-OHC and the ratio of 6β-hydroxycortisol to urinary free cortisol (6β-OHC/UFC) were measured before the first amiodarone administration. Trough plasma concentrations of amiodarone and N-desethylamiodarone (N-DEA) were measured after 79 ± 11 days (2nd period) and after 182 ± 25 days (3rd period). Electrophysiologic effects of amiodarone therapy were established with serial electrophysiologic studies in 9 of these patients at the baseline and after 79 ± 11 days (during the second period). Results: Both the 6β-OHC excretion and 6β-OHC/UFC ratio varied approximately 6-fold between the patients. We found significant inverse correlation between the 6β-OHC excretion and the trough plasma concentrations of amiodarone at the time of the 3rd period (rs = -0.58, p s = -0.64, p < 0.025). We were unable to detect any association between CYP3A activity and amiodarone pharmacodynamics. Conclusion: This study points toward important information value of CYP3A metabolizer status in the context of therapeutic drug monitoring of amiodarone.
