Pharmacokinetics of intraperitoneal epoetin alfa in patients on peritonealdialysis using an 8-hour "dry dwell" dosing technique

Pharmacokinetic studies of intraperitoneal (IP) epoetin alfa administered t o continuous ambulatory peritoneal dialysis (CAPD) patients have shown low bioavailability, primarily attributable to the dilutional effect of coadmin istered dialysate, However, bioavailability is improved by instilling the d ose into a dry peritoneum. The current study was designed to determine whet her absorption after administration into a dry peritoneum is improved by ex tending 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 c atheter and allowed to dwell for 8 hours, CAPD was then resumed. Blood samp les were collected for 96 hours after the dose. A 14-hour effluent dialysat e sample was collected to determine epoetin alfa recovery. Enzyme immunoass ay was used for epoetin alfa analysis of serum and effluent. Standard pharm acokinetic methods were employed for analysis of the serum concentration ti me data. The extent of epoetin alfa absorption was significantly greater th an previously reported for a 4-hour dry dwell. The mean (+/-SD) dose-normal ized area-under-the-curve (nlAUC(0-x)) using the 8-hour dry dwell dosing te chnique was 6,331 +/- 2,536 mlU . h/mL, This is significantly greater than the value of 2,589 +/- 1,450 mlU . 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 intra peritoneal route is improved by extending the time the dose resides in a dr y peritoneum. (C) 1999 by the National Kidney Foundation, Inc.