Renal clearance of gentamicin in cystic fibrosis

Abstract

This study was designed to corroborate previous observations of low serum concentrations of aminoglycosides after usual doses in patients with cystic fibrosis and to investigate possible mechanisms for this change. We studied gentamicin clearance after single and multiple intravenously administered doses in 10 non-acutely ill patients with mild to moderate CF. The data could best be described by a two-compartment model for drug elimination. The mean 1-hour serum concentration, mean volume of distribution, and mean total plasma clearance of gentamicin were not different from those reported for patients without CF. The similarity of the plasma and the renal gentamicin clearances, supported by the observations that greater than 80% of administered drug was excreted in the urine by 4 hours and that negligible amounts were detected in sweat, saliva, or sputum, implies that the kidney is the major route of elimination in patients with mild CF. The correlation of increased plasma gentamicin clearance as NIH score decreases supports the hypothesis that aminoglycoside pharmacokinetics are changed as the severity of disease increases. For patients with mild CF, standard doses of gentamicin (60 mg/m2) will give safe and therapeutic concentrations.