Comparison of intraperitoneal and subcutaneous epoetin alfa in peritoneal dialysis patients
Peritoneal Dialysis International. 1999;19((6):):578-82.
OBJECTIVE To compare the efficacy of intraperitoneal (i.p.) and subcutaneous (s.c.) administration of epoetin alfa in patients receiving peritoneal dialysis (PD). DESIGN A 32-week prospective, randomized, cross-over experimental design. SETTING Two university-based outpatient PD centers. PATIENTS Twenty adult PD patients receiving stable doses of s.c. epoetin alfa enrolled in the study. Thirteen patients completed 32 weeks of follow-up. INTERVENTION Patients were randomly assigned to receive either s.c. or i.p. epoetin alfa at the start of the study. Dose adjustments were made to maintain baseline hematocrit +/- 3 percentage points. Following 16 weeks of treatment, patients crossed over to the other route of administration for an additional 16 weeks. Intraperitoneal epoetin alfa was administered into an empty peritoneal cavity for approximately 8 hours before resuming dialysis. End-of-study i.p. epoetin alfa doses required to maintain target hematocrit were given twice weekly (n = 1), once weekly (n = 11), or once every other week (n = 1). All patients received iron supplements to maintain or exceed prestudy iron parameters. MAIN OUTCOME MEASURE Prior to the study, the primary outcome measure was defined as the difference in epoetin alfa dose between i.p. and s.c. administration. RESULTS Thirteen patients completed the study. The area under the dosing-requirement curve for i.p. epoetin alfa was larger than for s.c. administration (p = 0.0029), and the slope of the 16-week dose-requirement curve was greater for i.p. administration (p = 0.017), suggesting greater dose stability for s.c. administration. Paired analysis indicated greater i.p. intrapatient dose requirements (p < 0.0001). The mean difference in s.c. versus i.p. doses was 5000 +/- 1510 units per week. Some patients required escalating i.p. doses to maintain target hematocrit values. Iron administration and iron stores were similar in both groups. CONCLUSION Intraperitoneal epoetin alfa may be a suitable alternative for some patients for whom s.c. dosing is undesirable. Large i.p. versus s.c. dosing differences noted in a few patients are unexplained, but may result from interpatient variability in i.p. epoetin alfa absorption. Intraperitoneal dosing into an empty peritoneum can be done safely and effectively.
Pharmacokinetics of intraperitoneal, intravenous, and subcutaneous recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis
American Journal of Kidney Diseases. 1993;21((6):):635-42.
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)
Buffy coat transfusions in neonates with sepsis and neutrophil storage pool depletion
A randomized study was initiated in neonates with neutropenia (absolute peripheral neutrophil count less than 1,500/microL) and suspected bacterial infection. Twenty infants with proven infection were enrolled, nine of whom had depletion of bone marrow stores of maturing neutrophils (less than or equal to 7% metamyelocyte, band and mature forms per 100 nucleated cells). These nine were randomized to receive 15 mL/kg of either buffy coat transfusions (group 2) or plasma and blood products (group 3). The remaining 11 (group 1) were observed. Peripheral neutrophil counts were monitored to determine the neutrophil response to transfusions. There were ten of 11 patients in group 1, two of four in group 2, and two of five in group 3 who lived at least seven days. No complications of transfusion were noted. No difference in the rate of peripheral neutrophil increase was found among the three groups. The study was stopped when it became clear that sufficient numbers of patients could not be entered into the study, in a reasonable period of time, to prove or disprove a clinically significant improvement in outcome. Although in vitro testing of the buffy coat preparations showed normal function in three of four cases, the clinical quality of the buffy coats may have been inadequate because of poor availability of whole fresh blood less than 24 hours old. The role of neutrophil transfusions in these patients remains unclear.