title: Pharmacokinetics and pharmacodynamics of bumetanide in neonates treated with extracorporeal membrane oxygenation.
abstract: Eleven term neonates treated with extracorporeal membrane oxygenation received bumetanide to treat volume overload. All patients had stable renal function, no history of prior diuretic therapy, and no overt evidence of hepatobiliary disease or hypoalbuminemia. Pretreatment creatinine clearance was 35.2 +/- 4.5 ml/min per 1.73 m2 (range, 20.3 to 57.5). Bumetanide, 0.095 +/- 0.003 mg/kg, was administered for 2 minutes into the postmembrane side of the extracorporeal membrane oxygenation circuit. Serial plasma and urine samples were collected for measurement of bumetanide and electrolyte concentrations. Total plasma and renal clearances for bumetanide were 0.63 +/- 0.11 and 0.16 +/- 0.04 ml/min per kilogram, respectively. The steady-state volume of distribution (0.44 +/- 0.03 L/kg) and the elimination half-life (13.2 +/- 3.8 hours) were greater than similar values reported in previous studies of bumetanide disposition in premature and term neonates who were not treated with extracorporeal membrane oxygenation. At observed rates of bumetanide excretion, the diuretic, natriuretic, and kaliuretic responses were linear. Significant diuresis, natriuresis, and kaliuresis were observed, although the duration of these effects was less than expected given the prolonged renal elimination of bumetanide. Nonrenal elimination of bumetanide was variable (47.2% to 96.9%) but higher than expected; this may explain the relatively brief diuretic and kaliuretic response.
authors.affiliation: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock.
authors.forename: T G
authors.initials: TG
authors.lastname: Wells
authors.forename: J W
authors.initials: JW
authors.lastname: Fasules
authors.forename: B J
authors.initials: BJ
authors.lastname: Taylor
authors.forename: G L
authors.initials: GL
authors.lastname: Kearns
mesh_terms: D000704:Analysis of Variance; D002034:Bumetanide / Q000032:analysis / Q000493:pharmacokinetics* / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004231:Diuresis / Q000187:drug effects; D015199:Extracorporeal Membrane Oxygenation / Q000379:methods; D006207:Half-Life; D006333:Heart Failure / Q000453:epidemiology / Q000378:metabolism / Q000628:therapy; D006801:Humans; D007231:Infant, Newborn; D016018:Least-Squares Analysis; D012131:Respiratory Insufficiency / Q000453:epidemiology / Q000378:metabolism / Q000628:therapy; D013997:Time Factors
chemical_list: D002034:Bumetanide