The pharmacokinetics of ceftazidime in patients with impaired renal function and concurrent frusemide therapy

We have studied the pharmacokinetics of ceftazidime in 37 patients suffering from serious bacterial infections. All the patients had impairment of renal function and received moderate to high doses of frusemide concurrently. The doses of ceftazidime were given according to renal function as recommended by the manufacturer. Serum and urine samples were frequently collected, and drug concentrations measured by high performance liquid chromatography. The patients were grouped and evaluated according to renal function, mean (SD) creatinine clearances ranging from 70.1 (12.4) to 11.0 (3.2) ml.min-1. The pharmacokinetics of ceftazidime depended on renal function. A statistically significant increase in ceftazidime elimination half-life and decreases in urinary recovery, total body clearance, and renal clearance in proportion to the decrease in renal function were observed (p less than 0.05). The apparent volume of distribution also increased, but not significantly (p greater than 0.05). A linear correlation was found between the total body and renal clearances of ceftazidime and creatinine clearance. The extrarenal clearance increased from 3.9 to 14.0 ml.min-1 with decreasing renal function. Concurrent treatment with ceftazidime and moderate to high doses of frusemide did not impair renal function and no evidence of nephrotoxicity was found.