期刊
JOURNAL OF INTERNAL MEDICINE
卷 283, 期 1, 页码 93-101出版社
WILEY
DOI: 10.1111/joim.12682
关键词
amiodarone; cholesterol metabolism; desmosterol
BackgroundAmiodarone is an effective and widely used antiarrhythmic drug with many possible adverse effects including hypercholesterolaemia and hepatotoxicity. ObjectiveOur aim was to evaluate how long-term amiodarone treatment affects cholesterol metabolism. MethodsThe study population consisted of 56 cardiac patients, of whom 20 were on amiodarone (amiodarone + group) and 36 did not use the drug (amiodarone - group). We also studied a control group of 124 individuals selected randomly from the population. Cholesterol metabolism was evaluated by analysis of serum noncholesterol sterols by gas-liquid chromatography and gas chromatography-mass spectrometry. ResultsComparisons of serum lipids and noncholesterol sterols across the three groups showed increased serum triglyceride in users of amiodarone but no statistically significant group differences in total, LDL or HDL cholesterol or serum proprotein convertase subtilisin/kexin type 9 concentrations. Nor did the groups differ in the ratios of cholestanol or plant sterols to cholesterol in serum, suggesting that cholesterol absorption was unaltered. However, all users of amiodarone had very markedly elevated serum desmosterol concentrations: the desmosterol-to-cholesterol ratio (10(2) x mol mmol(-1)) averaged 1030.7 115.7 (mean +/- SE) in the amiodarone + group versus 82.7 +/- 3.4 and 75.9 +/- 1.4 in the amiodarone - and the population control groups (P < 0.001), respectively. ConclusionUse of amiodarone was associated with on average 12-fold serum desmosterol concentrations compared with the control groups. This observation is fully novel and suggests that amiodarone interferes with the conversion of desmosterol to cholesterol in the cholesterol synthesis pathway. Whether accumulation of desmosterol plays a role in amiodarone-induced hepatotoxicity deserves to be studied in the future.
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