Pharmacokinetic study of an oral cephalosporin, cefdinir, in hemodialysis patients

Abstract

The pharmacokinetics of cefdinir were investigated in six hemodialysis patients. For the present study, two tests were carried out, one with 4 h of hemodialysis and the other without hemodialysis. Cefdinir was given orally to each patient in a dose of 100 mg, and blood was collected serially for 48 h after dosing in the test without dialysis and for 72 h in the test with dialysis. In the test without dialysis, the maximum plasma concentration (Cmax) was 2.36 +/- 0.53 micrograms/ml (mean +/- standard deviation) and the time to Cmax was 9.00 +/- 2.45 h. The terminal elimination half-life (t1/2) and area under the concentration-time curve (AUC) were 16.95 +/- 1.20 h and 69.05 +/- 14.84 micrograms.h/ml, respectively. In the test with dialysis, t1/2 during hemodialysis decreased approximately to one-sixth of that obtained in the test without dialysis, although t1/2 in the latter elimination phase did not differ from that in the nondialysis test. AUC was reduced to 43% of that in the test without dialysis. The fractional removal of cefdinir by hemodialysis was 61%. These findings indicate that clearance of cefdinir is prolonged in patients with renal failure, and cefdinir is well removed by introduction of hemodialysis, although t1/2 (during hemodialysis) and AUC were two and eight times higher than the data previously reported for healthy volunteers, respectively. The pharmacokinetic data suggest that 100 mg of oral cefdinir once a day would result in a sufficient concentration in plasma in hemodialysis patients, but this remains to be confirmed by multiple-dose studies.

FIG. 1

Mean plasma cefdinir concentration-time profiles after a single oral administration of 100 mg to hemodialysis patients with and without hemodialysis.