Transperitoneal movement and pharmacokinetics of cefotiam and cefsulodin in patients on continuous ambulatory peritoneal dialysis.
The kinetics of cefotiam and cefsulodin were studied in plasma and dialysate after intravenous and intraperitoneal administration of 1 g to patients undergoing continuous ambulatory peritoneal dialysis. Instillation of autologous hemoglobin as a marker permitted calculation of the cavity volume and, hence, the rate of transfer to and from the peritoneal cavity with time. The patients were divided into 4 groups. Groups 1 and 2 were intravenously given cefotiam (5 patients) and cefsulodin (4 patients), respectively. Groups 3 and 4 (5 patients each) were given cefsulodin intraperitoneally. Group 3 did not have peritonitis, while the patients in Group 4 were studied during peritonitis. Blood and dialysate samples were obtained at selected times during the 5-hour dwell and, for plasma, until 24 hours after drug administration. Pharmacokinetic analysis of the data showed that only 6.0 and 8.7% of the intravenous doses of cefotiam and cefsulodin, respectively, were recovered in the dialysate at the end of the dwell. The net amounts of cefsulodin lost from the dialysate after intraperitoneal administration were 81 and 84%, in Groups 3 and 4 respectively. The peritoneal transfer clearances (using a unidirectional clearance model), calculated after intravenous (17 +/- 10 ml/min, Group 2) and intraperitoneal (17 +/- 5 ml/min, Group 3) administrations were the same. Mass balance of cefsulodin in the body and in the dialysate after intraperitoneal administration indicated that a significant amount (40%, Group 3) of the dose is unaccounted for. One explanation for this imbalance is retention of the drug in the peritoneal lining. This hypothesis is supported by the retention being lower in the peritonitis patients (less than 20%, Group 4), for whom the linings are expected to be partially eroded.
Brouard
R
R
Division of Clinical Pharmacology, Schools of Medicine and Pharmacy, University of California, San Francisco 94143-0446.
Tozer
T N
TN
Merdjan
H
H
Guillemin
A
A
Baumelou
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001692:Biological Transport; D015310:Cefotiam / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D002441:Cefsulodin / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D015312:Hemodialysis Solutions / Q000032:analysis; D006801:Humans; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D008875:Middle Aged; D010529:Peritoneal Cavity / Q000378:metabolism*; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010538:Peritonitis / Q000188:drug therapy
D015312:Hemodialysis Solutions; D015310:Cefotiam; D002441:Cefsulodin