DISPOSITION OF DRUGS IN CYSTIC-FIBROSIS .4. MECHANISMS FOR ENHANCED RENAL CLEARANCE OF TICARCILLIN

To investigate the hypothesis that renal secretion of penicillins is e nhanced in cystic fibrosis the maximal tubular secretion rate (T(max)) of ticarcillin and the serum concentration of ticarcillin at half-max imal secretion rate (TC50) were determined in patients with cystic fib rosis (n = 6) and control subjects (n = 6). Each subject received thre e consecutive constant-rate intravenous infusions of ticarcillin (4, 1 3, and 70 mg/kg/hr; 2 1/2 hours each) simultaneously with a constant-r ate (30 mg/kg/hr) infusion of inulin. Urine samples were collected at 1/2-hour intervals and serum samples at the midpoint of the urine coll ections. Ticarcillin and inulin concentrations in serum and urine were determined by high-performance liquid chromatographic and a spectroph otometric method, respectively. Ticarcillin serum protein binding was determined by ultrafiltration. Steady-state ticarcillin serum concentr ations were achieved at all three infusion rates. The TC50 was signifi cantly lower (p < 0.05) in patients with cystic fibrosis (33.7 +/- 12. 2 mug/ml) compared with that in control subjects (77.6 +/- 38.4 mug/ml ). In contrast, the T(max) was similar (cystic fibrosis, 0.25 +/- 0.12 mg/min/kg; control, 0.22 +/- 0.14 mg/min/kg; p > 0.05). These data in dicate that renal clearance of penicillins is enhanced in cystic fibro sis because of greater affinity of the renal secretory system for thes e drugs.