The disposition of recombinant human erythropoietin (EPOCH) after subcutaneous administration (1) : Pharmacokinetics of non-labeled EPOCH in rats and dogs

Abstract

We studied the pharmacokinetics of EPOCH after subcutaneous administration to male rats and dogs. The EPOCH concentrations in samples were measured by RIA.
1. In rats given EPOCH subcutaneously at the doses of 1, 5 and 25μg/kg, the concentrations of EPOCH reached the peak at 8 to 12 hours after dosing and declined monoexponentially with a half-life ranging from 7.52 to 10.89 hours. MRT of EPOCH after sc dosing ranged from 15.82 to 17.71 hours at any dose levels. F value (AUCsc; AUCiv), which ranged from 0.45 to 0.64, tend to increase as dose increase. Cumulative urinary excretions within 48 hours after dosing were 2.7, 1.2 and 0.9% of dose at 1, 5 and 25μg/kg.
2. In male Beagle dogs given EPOCH subcutaneously at the dose of 5μg/kg, pharmacokinetic parameters of EPOCH were obtained as follows ; C_max was 22.37±2.10ng/ml, T_max was 6.50±2.50h, AUC was 544.32±22.25ng·h/ml, MRT was 23.25±1.55h, and T_1/2 was 12.71±0.47h. F value was 0.46. Cumulative amount of EPOCH excreted in urine for 72h was 0.32±0.14% of dose, and renal clearance was 0.39±0.17ml/h/kg.
3. The molecular profile of immunoreactive materials, identified by gel filtration in plasma samples from rats and dogs given EPOCH subcutaneously, showed the single peak corresponding to the standard EPOCH at any sampling times. These results suggested that the immunoreactive material detected by RIA represented the unchanged EPOCH, and that no immunoreactive metabolite might be present in plasma and urine samples of rats given non-labelled EPOCH subcutaneously.