Pharmacokinetics of intraperitoneal epoetin alfa in patients on peritoneal dialysis using an 8-hour "dry dwell" dosing technique.
Pharmacokinetic studies of intraperitoneal (IP) epoetin alfa administered to continuous ambulatory peritoneal dialysis (CAPD) patients have shown low bioavailability, primarily attributable to the dilutional effect of coadministered dialysate. However, bioavailability is improved by instilling the dose into a dry peritoneum. The current study was designed to determine whether absorption after administration into a dry peritoneum is improved by extending the dry dosing period from 4 to 8 hours. The pharmacokinetics of a single 100-unit/kg IP epoetin alfa dose were studied in 8 noninfected CAPD patients. The dose was instilled into a dry peritoneum via the peritoneal catheter and allowed to dwell for 8 hours. CAPD was then resumed. Blood samples were collected for 96 hours after the dose. A 14-hour effluent dialysate sample was collected to determine epoetin alfa recovery. Enzyme immunoassay was used for epoetin alfa analysis of serum and effluent. Standard pharmacokinetic methods were employed for analysis of the serum concentration time data. The extent of epoetin alfa absorption was significantly greater than previously reported for a 4-hour dry dwell. The mean (+/-SD) dose-normalized area-under-the-curve (nlAUC(0-infinity)) using the 8-hour dry dwell dosing technique was 6,331 +/- 2,536 mIU. h/mL. This is significantly greater than the value of 2,589 +/- 1,450 mIU. h/mL (two-sided P value = 0.002) from a previous study in which patients received the same 100-unit/kg dose using a 4-hour dry dwell. The absorption of epoetin alfa administered by the intraperitoneal route is improved by extending the time the dose resides in a dry peritoneum.
Taylor
C A
CA
Department of Medicine and School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA. cataylor@utep.edu
Kosorok
M R
MR
Zimmerman
S W
SW
Johnson
C A
CA
D000293:Adolescent; D000328:Adult; D000368:Aged; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D011994:Recombinant Proteins; D016896:Treatment Outcome
D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa