The pharmacokinetics of intraperitoneal erythropoietin administered undiluted or diluted in dialysate

Perit Dial Int. 1992;12(4):369-72.

Abstract

Objective: To compare the bioavailability of intraperitoneal erythropoietin (EPO) administered undiluted versus diluted in 2 L of dialysis fluid.

Design: Group 1 patients received one dose of EPO, 400 U/kg BW given with vehicle only. This dwelled for 8 hours after which 2 L of dialysate were infused. Group 2 patients received the same dose of EPO diluted in 2 L of dialysate which dwelled for 8 hours. Both groups resumed their CAPD regimen after the first 8 hours. Blood levels of EPO were measured for 24 hours in both groups.

Setting: The Home Peritoneal Dialysis Unit, Toronto Hospital, Western Division.

Patients: The participants were on CAPD for at least three months, free of peritonitis, and had no abnormalities of peritoneal transport. Three patients took part in both arms of the study, and there were 6 patients altogether in each group.

Results: When EPO was administered undiluted, there was a greater than ninefold increase in bioavailability of the hormone as measured by the area under the curve (AUC), compared to when the same dose was diluted in 2 L of dialysis fluid.

Conclusions: The previous studies that reported low bioavailability of intraperitoneal EPO used the hormone diluted in dialysate. The current findings suggest that if EPO is given in the dry peritoneal cavity, the bioavailability is greatly improved and may be clinically effective. Intraperitoneal instillation may prove to be an alternative route for EPO in the peritoneal dialysis patient unable or unwilling to receive subcutaneous injections. We are currently studying the effectiveness of undiluted intraperitoneal EPO in CAPD patients.

Publication types

  • Comment
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anemia / drug therapy*
  • Anemia / etiology
  • Biological Availability
  • Dialysis Solutions*
  • Erythropoietin / administration & dosage*
  • Erythropoietin / pharmacokinetics*
  • Erythropoietin / therapeutic use
  • Humans
  • Infusions, Parenteral
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / therapy
  • Middle Aged
  • Peritoneal Dialysis, Continuous Ambulatory*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacokinetics
  • Recombinant Proteins / therapeutic use
  • Time Factors

Substances

  • Dialysis Solutions
  • Recombinant Proteins
  • Erythropoietin