Je. Sullivan et al., DOSE-RANGING EVALUATION OF BUMETANIDE PHARMACODYNAMICS IN CRITICALLY ILL INFANTS, Clinical pharmacology and therapeutics, 60(4), 1996, pp. 424-434
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.