Influence of protein and calorie malnutrition on the pharmacokinetics and pharmacodynamics of bumetanide in rats.

Bumetanide is a loop diuretic that is used for the treatment of edema and hypertension. The rapidly developing syndrome of extracellular fluid overload in some malnourished children has been successfully treated with furosemide, another loop diuretic, and digoxin; however, similar studies with bumetanide have not been conducted to date. Therefore, in the present study, the influence of dietary protein deficiency on the pharmacokinetics and pharmacodynamics of bumetanide was investigated after intravenous (i.v.) bolus and oral administration of bumetanide to male Sprague-Dawley rats fed on 23% (control rats) or 5% [protein and calorie malnutrition (PCM) rats] protein diet ad libitum for 4 weeks. After an i.v. dose of bumetanide, 1 mg/100 g body weight, the mean values of renal clearance and percentages of dose excreted as unchanged bumetanide in an 8-h urine sample were 166 and 154% higher, respectively, in PCM than control rats; however, nonrenal clearance (CLNR) was 28% lower. The decrease in nonrenal clearance in PCM rats might be because of the decrease in nonrenal metabolism of bumetanide in PCM rats. The urine output per 100 g of body weight was not significantly different between the two groups of rats after i.v. administration, although the amount of bumetanide excreted in the 8-h urine sample per 100 g body weight increased significantly in PCM rats. These results could be explained by the fact that the dose of bumetanide used results in urinary excretion rate of bumetanide at the plateau of the concentration-effect relationship.(ABSTRACT TRUNCATED AT 250 WORDS)