Individual variability of amiodarone distribution in plasma and erythrocytes: implications for therapeutic monitoring.
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 QT (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 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 = 0.29 p less than 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 less than 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.
Maling
T J
TJ
Department of Medicine, Wellington School of Medicine, New Zealand.
Siebers
R W
RW
Burgess
C D
CD
Taylor
C
C
Purdie
G
G
D000328:Adult; D000368:Aged; D000638:Amiodarone / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D004912:Erythrocytes / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
C036116:desethylamiodarone; D000638:Amiodarone