Increased nonrenal clearance and increased diuretic efficiency of furosemide in cystic fibrosis

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Abstract
The pharmacokinetics of furosemide and its diuretic effect were studied in six patients with cystic fibrosis (CF) and in six age-matched healthy volunteers. Furosemide was given intravenously at a dose of approximately 0.5 mg/kg. Renal excretion of furosemide was decreased in CF because nonrenal clearance was more than twice as high as in controls (p = 0.03). Nonrenal clearance correlated with the volume of distribution (r2 = 0.52, p = 0.01), which makes a difference in the distribution and binding determinants for clearance. Another reason for increased nonrenal clearance could be induction of drug metabolism in CF, but the excretion of furosemide conjugate did not differ significantly between the groups. Although 26% less furosemide was excreted in CF than in controls (p = 0.03), the diuretic response (calculated as excretion of water and electrolytes) did not differ. Thus the diuretic efficiency was higher in CF for Na+ (p = 0.02), Cl- (p = 0.01), K+ (p = 0.07), and volume (p = 0.005). This difference is probably secondary to the different rates of delivery of furosemide into urine.