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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Pharmacokinetics of esmolol and ASL-8123 in renal failure.

The effect of renal function on the pharmacokinetics of esmolol, an ultra-short-acting beta-adrenergic blocker, and its major metabolite, ASL-8123, was examined in six healthy control subjects, six patients maintained on hemodialysis, and six patients on continuous ambulatory peritoneal dialysis (CAPD). In addition, the impact of hemodialysis and CAPD on removal of esmolol and ASL-8123 was determined. Multiple blood, urine, and dialysate samples were collected during a 72-hour period and assayed for esmolol and ASL-8123 by HPLC. The pharmacokinetic disposition of esmolol was not significantly altered by renal failure. Mean (+/- SD) total body clearance for esmolol was 171.4 +/- 69.8, 249.8 +/- 176.3, and 265.3 +/- 143.1 ml/min/kg for the control, hemodialysis, and CAPD patients, respectively. Mean elimination half-life (t1/2) was 7.2 minutes in control subjects compared with 7.1 and 8.0 minutes for the hemodialysis and CAPD groups, respectively. The apparent volume of distribution of esmolol did not differ significantly among the three groups. ASL-8123 was shown to accumulate in patients with renal failure, as evidenced by a mean maximum blood concentration of 42.8 +/- 12.2 micrograms/ml in the control group compared with 76.1 +/- 23.9 and 87.1 +/- 20.4 micrograms/ml in the hemodialysis and CAPD groups, respectively (p less than 0.05). The elimination t1/2 of ASL-8123 was prolonged in patients with renal failure, averaging more than 42 hours compared with only 4 hours in the control subjects. Approximately 20% of the esmolol dose as ASL-8123, was removed by either hemodialysis or CAPD, contributing minimally to the elimination of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)[1]


  1. Pharmacokinetics of esmolol and ASL-8123 in renal failure. Flaherty, J.F., Wong, B., La Follette, G., Warnock, D.G., Hulse, J.D., Gambertoglio, J.G. Clin. Pharmacol. Ther. (1989) [Pubmed]
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