1983 Volume 31 Issue 11 Pages 1055-1062
The pharmacokinetics of cefpiramide (CPM), a new parenteral semisynthetic cephalosporin derivative, were studied in 6 healthy adult volunteers and 31 patients with impaired renal function after the administration of a single 500-mg dose intravenously. CPM concentrations in serum and urine were determined by the agar well method with Escherichia coli NIHJ as a test organism and sensitive test agar as a test medium. Endogenous creatinine clearance was used as an indicator of renal function. Pharmacokinetic parameters were estimated from a two-compartment open model, using a NONLIN nonlinear regression program. The serum levels in patients with renal impairment were slightly higher than those in healthy volunteers for varying periods from 30min. to 24hr. postdrug. The mean serum half-life during β-phase, 4.06hr. in normal subjects, were slightly prolonged in patients with impaired renal function; the prolongation, however, was not remarkable. The mean 24-hr. urinary recovery rate of CPM was 21.5% in normal subjects and decreased with decreasing renal function to 0.6% in 10 hemodialysis patients. There was no significant relationship between the creatinine clearance and pharmacokinetic parameters obtained from the serum concentration-time curve; serum half-life during β-phase, elimination rate constant, distribution volume or area under the serum concentration curve. On the contrary, the urinary recovery rate and renal clearance of the drug were decreased with a corresponding diminution of renal function. The mean serum half-life during β-phase was not shortened by hemodialysis. These results suggest that injected CPM is mainly excreted by other organs than the kidney, probably the liver.
