The disposition and dynamics of labetalol in patients on dialysis
1986
The disposition of labetalol was assessed in 16 patients on dialysis after intravenous dosing with 0.7 to 1.0 mg/kg during an interdialytic period and just before hemodialysis (n = 8) and during continuous ambulatory peritoneal dialysis (CAPD) (n = 8). The plasma concentration time data exhibited triexponential decay in all patients. The terminal t½ of labetalol was 12.90 ± 4.68 hours, the total body clearance was 1198.2 ± 249.4 ml/min, and the AUC was 921.4 ± 175.2 ng hr/ml during the interdialytic period. No significant changes were observed in these parameters after dosing with labetalol just before dialysis. The hemodialysis clearance of labetalol was 30.67 ± 5.49 ml/min, and only 0.189 ± 0.042 mg of labetalol was removed by hemodialysis. The terminal t½ averaged 13.05 ± 6.32 hours during CAPD. Steady-state volume of distribution, total body clearance (Clp), and CAPD clearance were 10.39 ± 2.77 L/kg, 1397.2 ± 372.3 ml/min, and 1.94 ± 0.65 ml/min, respectively. The fraction of the dose recovered in the CAPD dialysate during the 72-hour study period was 0.14% ± 0.09%. The decay of the antihypertensive effect of labetalol was gradual and paralleled the decline in the log plasma concentration. There was a significant correlation between labetalol plasma concentration and the fall in supine diastolic and mean blood pressure after the interdialytic dose and during CAPD. Although labetalol is removed by dialysis, dialysis does not significantly enhance Clp.
Clinical Pharmacology and Therapeutics (1986) 40, 462–468; doi:10.1038/clpt.1986.207
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