The relationships between size of loading dose and drug concentration, size of maintenance dose and drug concentration, and pulmonary and cutaneous adverse side effects and drug dosage were examined in patients given amiodarone. Amiodarone and metabolite concentrations in plasma and red cell samples were measured by specific high-pressure liquid chromatography. During drug loading, a daily dose schedule of 1600 mg/day produced significantly higher drug concentrations than did a loading dose schedule of 800 mg/day. During maintenance therapy, amiodarone dosage correlated with drug concentrations but with a wide interpatient variability for any given dosage level. The ratio of desethylamiodarone to amiodarone remained relatively constant over different dosage or drug concentration ranges, but increased with duration of treatment, suggesting a time-dependent metabolic function that may be analogous to the time-dependent attainment of maximal antiarrhythmic effect. The occurrence of pulmonary toxicity from amiodarone was not related to duration of treatment or cumulative dose of drug, buy may relate to the magnitude of the maintenance dose of amiodarone. Blue skin discoloration occurred in 19 (36%) of 53 patients receiving amiodarone for longer than 17 months, and may relate to the cumulative dose.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine