Individual Variability of Amiodarone Distribution in Plasma and ErythrocytesImplications for Therapeutic Monitoring
作者:
Timothy Maling,
Robert Siebers,
Carl Burgess,
Celia Taylor,
Gordon Purdie,
期刊:
Therapeutic Drug Monitoring
(OVID Available online 1989)
卷期:
Volume 11,
issue 2
页码: 121-126
ISSN:0163-4356
年代: 1989
出版商: OVID
关键词: Amiodarone;Plasma;Erythrocytes;Variability.
数据来源: OVID
摘要:
The complexity of amiodarone disposition in blood and tissues gives rise to difficulty in determination of optimal therapeutic monitoring strategies. We have defined the within-patient variability of plasma and erythrocyte amiodarone and desethylamiodarone concentrations and electrocardiogram intervals [PR and corrected QTc)] in 27 patients each sampled on three to four occasions during long-term stable amiodarone therapy. All individual repeated measurements were included in the concentration-effect analysis. The mean within-patient coefficients of variation for amiodarone and desethylamiodarone were significantly greater in erythrocytes, 46.0 and 24.5%, respectively, compared with plasma, 12.7 and 12.3%. Amiodarone and desethylamiodarone were strongly correlated (r= 0.89 p < 0.0001) in plasma but only weakly in erythrocytes (r= 0.29 p < 0.004). There was a 10-fold variability in erythrocyte amiodarone for a given plasma level. These data emphasize the highly variable cellular distribution of amiodarone and desethylamiodarone in the same patient on stable dosage over time. Plasma amiodarone was significantly correlated with dosage (r= 0.98), and percent change in QTc, (r= 0.56, p < 0.0001), but there was a fourfold variation in plasma amiodarone for a given QTc.-Side-effect frequency was not related to plasma or erythrocyte amiodarone or desethylamiodarone concentrations. A clinically useful relationship between plasma concentration and effect could not be consistently demonstrated for amiodarone in the same individual during stable dosage.
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