Pharmacokinetic study of recombinant human erythropoietin treatment in pre-dialysis end stage renal disease patients.

We treated pre-dialysis ESRD patients with recombinant human erythropoietin (rHuEPO) by either the subcutaneous (s.c.) or intravenous (i.v.) route, and investigated the pharmacokinetics of rHuEPO. Twenty patients were divided equally into two groups by the difference in route, and rHuEPO was administered once per week for 8 weeks. The dose was 3,000 and 6,000 IU in the s.c. group and 3,000, 6,000 and 9,000 IU in the i.v. group. Although anemia was corrected significantly in both groups, residual renal function was not affected significantly. Pharmacokinetic study revealed that none of the parameters changed between the initial and final treatments in any of the groups. Area under the curve (AUC) and maximum concentration (Cmax) was consistently smaller in the s.c. --than in the i.v.--treated group. Mean residence time (MRT) was 3 times longer in the s.c. group than in the i.v. group. Bioavailability of rHuEPO in the s.c. group was around 35%, and mean absorption time (MAT) was around 25 hours. Though the s.c. route has been reported to be more effective for correcting anemia with rHuEPO than the i.v. route when rHuEPO was administered either twice or three times per week, our study demonstrated that the effect of rHuEPO was almost equal between the s.c.-treated and i.v.-treated groups when rHuEPO was administered once per week. We assume that this equivalent degree of efficacy in the s.c. group in spite of low values of AUC and Cmax might be derived by the longer MRT. Thus, we consider that MRT is an important factor and the efficacy of rHuEPO should be investigated with evaluation of MRT when the administration route is different.