Pharmacokinetics of cefpiramide in volunteers with normal or impaired renal function.

The pharmacokinetics of a single 2.0-g intravenous dose of cefpiramide in patients with normal or impaired renal function were studied. Serial concentrations in serum and urine were measured by using high-performance liquid chromatography, and the effect of the concentration in serum on protein binding was assessed. Thirty patients (ten with creatinine clearances of greater than 80 ml/min, ten with creatinine clearances between 10 and 80 ml/min, and ten on dialysis) were studied. The concentration-time curve of cefpiramide was best described by an open two-compartment model. The elimination half-lives in patients with normal or impaired renal function or those on dialysis were 5.41 +/- 1.44, 8.3 +/- 2.82, and 8.38 +/- 4.06 h, respectively, and the serum clearances in the same groups were 2.0 +/- 0.84, 1.29 +/- 0.45, and 2.04 +/- 1.10 liters/h, respectively. There were no significant differences in any of the parameters among the three groups of patients. In patients with normal or impaired renal function, protein binding varied between 93.0 +/- 1.3% at 304.4 micrograms/ml and 99.3 +/- 0.8% at 41.1 micrograms/ml and was linearly and inversely related to the cefpiramide concentration in serum. In patients on dialysis, protein binding was significantly lower (P less than 0.05) and varied between 88.5 +/- 7.1% at 173.4 micrograms/ml to 94.9 +/- 4.8% at 46.8 micrograms/ml. In patients with normal or abnormal renal function, renal cefpiramide clearance decreased linearly with declining renal function, whereas plasma clearance was maintained. Therefore, nonrenal elimination becomes more important as renal impairment progresses.