Pharmacokinetics of intraperitoneal, intravenous, and subcutaneous recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis.
The pharmacokinetics of recombinant human erythropoietin (Epo) were compared after mean single 99.1 U/kg intraperitoneal (IP), intravenous (i.v.), and subcutaneous (SC) doses in eight noninfected patients on peritoneal dialysis in a randomized, three-way, cross-over fashion. Continuous ambulatory peritoneal dialysis was performed in all patients on the days of the study. The IP dose was instilled into an empty peritoneum; total dwell time was 10 hours (4 hours dry, 6 hours with 2 L of peritoneal dialysis fluid). Blood samples were collected for 96 hours following IP and SC Epo, and for 72 hours following i.v. Epo. For the IP dose, a 10-hour effluent dialysate sample was collected to determine Epo recovery. Enzyme immunoassay was used for Epo analysis. The mean apparent volume of distribution was 0.05 L/kg, equivalent to 4.5% of total body weight; the mean total body clearance was 0.08 mL/min/kg. All eight patients exhibited multiexponential decay in serum Epo concentrations following i.v. Epo. Absorption of IP Epo was significantly greater than previous reports, presumably due to its administration into a dry peritoneum. The maximum concentrations following the IP and SC doses were nearly identical, but amounted to only 5% of the maximum concentrations for the i.v. dose. Subcutaneous Epo took nearly twice as long as IP Epo to achieve peak serum concentrations (17.1 +/- 5.0 hours v 9.4 +/- 1.9 hours). Compared with the IP route, the SC dose achieved a higher area under the serum concentration time curve from time 0 to 96 hours (AUC0-96; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
School of Pharmacy, University of Wisconsin Hospital and Clinics, Madison 53792-1530.
A
A
Ateshkadi
C A
CA
Johnson
L L
LL
Oxton
T G
TG
Hammond
W S
WS
Bohenek
S W
SW
Zimmerman
D000042:Absorption; D000328:Adult; D000368:Aged; D001682:Biological Availability; D004921:Erythropoietin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D004921:Erythropoietin