Pharmacokinetics of Cefamandole in Patients Undergoing Hemodialysis and Peritoneal Dialysis

Abstract

The pharmacokinetics of cefamandole nafate, a new parenteral cephalosporin derivative, were evaluated in 11 patients with chronic renal failure (creatinine clearance less than 5 ml/min), including five patients during hemodialysis, four patients during routine peritoneal dialysis, and two patients during the interdialytic period. Peak serum levels of cefamandole were comparable to those observed in patients with normal renal function. Clearance of the drug during the interdialytic period and during hemodialysis and peritoneal dialysis was minimal, with a resultant significant prolongation of serum half-life. The nondialyzability of cefamandole is in contrast with reported studies of cephalothin, where significant reduction of the serum half-life was achieved during hemodialysis but not peritoneal dialysis. The concentration of cefamandole in the peritoneal dialysate after parenteral administration was observed to be bactericidal for many gram-negative pathogens and, with the exception of Streptococcus faecalis , most gram-positive organisms found in bacterial peritonitis in patients with severe renal failure. The present data suggest that if stable bactericidal serum levels of cefamandole are to be maintained during hemodialysis and peritoneal dialysis, a parenteral loading dose must be administered followed by one-half the loading dose every half-life.

Pharmacokinetics of Oral Cephradine in Continuous Ambulatory Peritoneal Dialysis Patients

“…This study demonstrates that the peritoneal clearance of cephradine is similar to the low peritoneal clearances reported for many other cephalosporins [4,[7][8][9][10]. While the dialysate cephradine concentrations achieved follow ing a 500-mg dose are adequate to treat many gram-posi tive organisms frequently responsible for CAPD-associated peritonitis, they are inadequate against one of the most common causes of peritonitis, Staphylococcus epidermidis, for which the MIC90 is reported to exceed 25 ug/ml [11].…”

Treatment of Hospital‐Acquired Peritoneal Dialysis Infections with Cefamandole

“…It is probable that the intravenous dosage which we used could safely be halved without loss of efficacy. 9 Previous studies indicate that the mean serum level achieved in our patients was at least 4 times greater than the MIC of cefamandole for the organisms we encountered. 12 We have found cefamandole used both systemically and locally to be an effective single antibiotic in the initial treatment of clinically diagnosed peritoneal dialysis infections: This regimen usually relieves symptoms within 48 hours and has the added advantage of short duration and a low relapse rate.…”

“…This may represent the effect discussed above or be a reflection of differing clearances depending on residual renal function or the degree of peritoneal inflammation. It is probable that the intravenous dosage which we used could safely be halved without loss of efficacy 9 . Previous studies indicate that the mean serum level achieved in our patients was at least 4 times greater than the MIC of cefamandole for the organisms we encountered 12 …”

“…In normal subjects the renal clearance of cefamandole exhibits saturation kinetics similar to those of benzylpenicillin, but the individual subject shows unexplained wide variations in serum levels 8 . Very little is removed by peritoneal or haemodialysis — only 13 per cent of a 1 gram intravenous bolus can be recovered from the peritoneal cavity during a subsequent 12 hours dialysis 9 . This together with the need for rapid treatment led us to use the drug both locally and systemically as indicated with other cephalosporins 10 .…”

Pharmacokinetics of β-Lactam Antibiotics

“…There have been a number of studies involving the intravenous or intramuscular administration of cefamandole nafate to patients with varying degrees of renal dysfunction (HOFFLER et al 1978;ApPEL et al 1976;AHERN et al 1976;MELLIN et al 1977;MEYERS and HIRSCHMAN 1977;LEROYet al 1977;CAMPILLO et al 1979;BROGARD et al 1979 a;RIZZO et al 1979;CZERWINSKI and PEDERSON 1979). In general, serum levels of antimicrobial activity were elevated and the apparent serum half-life increased as kidney function decreased.…”