cefdinir and Kidney-Failure--Chronic

Cefdinir (CAS 91832-40-5) was administered orally as a 100-mg capsule (Cefzon) to a total of 12 patients with chronic renal failure undergoing continuous ambulatory peritoneal dialysis (CAPD) to investigate changes in the serum concentrations, excretion rate into the dialysate and serum-protein binding of cefdinir. Cmax values were 1.64-4.34 micrograms/ml, t1/2 values were 10.8-21.9 h., and AUC values were 31.1-73.1 micrograms.h/ml (0-30 h) in four patients given a single oral dose of 100 mg of cefdinir as a capsule. About 1 microgram/ml of cefdinir had still remained in the blood of all the patients 24 h after administration. The serum concentrations of cefdinir were dose-dependent in four patients of each group who were given an oral daily dose of 100 mg for 3 to 8 days and 200 mg (2 capsules) for 4 to 14 consecutive days. No marked change in laboratory test values or clinical symptoms before and after administration were observed in these dose regimes. Protein levels of 5.17-5.71 g/day were eliminated from the peritoneal dialysate and urine. Cefdinir inhibited 90 to 100% of the clinical isolates such as Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and other enteric bacteria causing catheter infection and peritonitis, and its antibacterial activity was stronger than that of amoxicillin (CAS 26787-78-0) or cefaclor (CAS 53944-73-3) against these clinical isolates.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Bacteria; Blood Proteins; Cefdinir; Cephalosporins; Dialysis Solutions; Female; Half-Life; Humans; Kidney Failure, Chronic; Male; Microbial Sensitivity Tests; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Protein Binding

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.

Topics: Administration, Oral; Adult; Cefdinir; Cephalosporins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

An assessment was made of the serum protein binding of representative oral cephems (cefdinir, cefixime and ceftibuten) for sera from healthy subjects (HS) and patients with chronic renal failure (CRF) using an application of equilibrium dialysis under a same set of conditions in vitro. The protein binding capacity of oral cephems in CRF patients being treated with continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD) was significantly less than that in HS, and a marked increase in free drug concentration was observed. While examining the protein binding of oral cephems with heparin in patients on HD, binding capacity decreased significantly immediately following the completion of dialysis compared to that prior to dialysis. On the other hand, the protein binding of oral cephems did not change when used nafamostat mesilate as an anticoagulant. The addition of palmitic acid (PA), a common non-esterified fatty acid (NEFA), to pooled sera from HS caused the binding capacity of oral cephems to decrease, accompanied by increase in PA concentration. It appears from these findings that changes in the binding capacity of oral cephems with HD have possibly been caused by increase in NEFA due to activation of lipase when heparin was used as an anticoagulant. In conclusion, changes in the protein binding capacity of oral cephems in CRF patients should be taken into consideration in attempts to avoid possible side effects.

Topics: Carrier Proteins; Cefdinir; Cefixime; Cefotaxime; Ceftibuten; Cephalosporins; Humans; Kidney Failure, Chronic; Palmitic Acid; Palmitic Acids; Renal Dialysis