DOSE-RANGING EVALUATION OF BUMETANIDE PHARMACODYNAMICS IN CRITICALLY ILL INFANTS

Citation
Je. Sullivan et al., DOSE-RANGING EVALUATION OF BUMETANIDE PHARMACODYNAMICS IN CRITICALLY ILL INFANTS, Clinical pharmacology and therapeutics, 60(4), 1996, pp. 424-434
Citations number
39
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00099236
Volume
60
Issue
4
Year of publication
1996
Pages
424 - 434
Database
ISI
SICI code
0009-9236(1996)60:4<424:DEOBPI>2.0.ZU;2-8
Abstract
Objectives: Determine the diuretic effects of single intravenous doses of bumetanide in volume-overloaded critically ill infants, Methods: p rospective, open-label study was carried out in 56 infants aged 0 to 6 months who required diuretic therapy. Each patient received a single intravenous dose of bumetanide. Doses selected in sequential order ran ged from 0.005 to 0.10 mg/kg. Determinations of mine volume, electroly tes, creatinine levels, and osmolality were performed before (collecte d from -2 to -4 hours to time 0) and at 1, 2, 3, 4, 6, and 12 hours af ter bumetanide dosing. Serum samples collected at time 0 and at 5, 15, 30, 60, 120, 180, 240, 360, and 480 minutes and urine aliquots collec ted at time 0, 0 to 1, 1 to 2, 2 to 3, 3 to 4, 4 to 6, and 6 to 12 hou rs were analyzed for bumetanide concentration. Individual changes in u rine Bow rate and electrolyte excretion were plotted against correspon ding bumetanide excretion rates, taken as the effective dose of the dr ug. Results: Peak bumetanide excretion rates increased linearly with i ncreasing doses of drug Time course patterns for urine Bow rate and el ectrolyte excretion were similar for all dosage groups. Urine how rate and electrolyte excretion increased Linearly up to a bumetanide excre tion rate of approximately 7 mu g/kg/hr and either plateaued (urine Bo w rate) or declined at a bumetanide excretion rate of >10 mu g/kg/hr. Diuretic efficiency of bumetanide was maximal at doses of 0.005 to 0.0 10 mg/kg brit decreased at higher doses. Conclusions: Maximal diuretic responses occurred at a bumetanide excretion rate of about 7 mu g/kg/ hr, corresponding to doses of 0.035 to 0.040 mg/kg. Higher doses produ ced a proportionately higher bumetanide excretion rate but no increase d diuretic effect Lower doses of bumetanide had the greatest diuretic efficiency, suggesting that continuous infusion of lon doses of bumeta nide or intermittent low-dose boluses may produce optimal diuretic res ponses in critically ill infants.