PHARMACOKINETICS OF BUMETANIDE IN CRITICALLY ILL INFANTS

Objective: Define the pharmacokinetics of bumetanide after single intr avenous doses in volume-overloaded critically ill infants. Methods: A prospective, open-label study was carried out in a group of 58 infants aged 0 to 6 months who required diuretic therapy. Each patient receiv ed a single dose of intravenous bumetanide. Doses selected in sequenti al order ranged from 0.005 to 0.10 mg/kg. Hematologic and serum chemis try studies were performed before and at 6 and 24 hours after bumetani de administration. Determinations of urine volume and chemistries were performed before (collected from -2 to -4 hours to time 0) and at 1, 2, 3, 4, 6, and 12 hours after bumetanide dosing. Serum samples collec ted at time 0 and at 5, 15, 30, 60, 120, 180, 240, 360, and 480 minute s and urine collected at time 0 and at 0 to 1, 1 to 2, 2 to 3, 3 to 4, 4 to 6, and 6 to 12 hours were analyzed for bumetanide concentration. Data were evaluated by standard noncompartmental pharmacokinetic tech niques.Results: Peak serum bumetanide concentrations occurred at 5 min utes after bumetanide administration. Area under the curve and peak se rum bumetanide concentrations showed linear increases over the twentyf old dose range; whereas beta volume of distribution, volume of distrib ution at steady state, clearance, renal clearance, half-life, and mean residence time values were independent of dose. Peak urinary excretio n rates of bumetanide increased linearly with increasing doses. The me an percent of bumetanide recovered in the urine from 0 to 12 hours was 40%+/-15% of the administered dose. Conclusions: Distribution and eli mination kinetics of bumetanide were similar in all patients. Eliminat ion kinetics were first order over the dose range of 0.005 to 0.10 mg/ kg. Pharmacokinetic parameter estimates (beta volume of distribution, volume of distribution at steady state, clearance, renal clearance, ha lf-life, and mean residence time) were independent of the dose of bume tanide administered. Single doses of bumetanide up to 0.10 mg/kg appea r to be well tolerated in acutely ill volume-overloaded infants aged 0 to 6 months.