Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in rats

The pharmacokinetics and pharmacodynamics of recombinant human erythropoietin (rh-EPO; CAS for EPO: 11096-26-7) after repeated intravenous and subcutaneous administrations in rats were studied. Administration of rh-EPO by both routes caused significant increases in hematocrit. The pharmacokinetics of rh-EPO after intravenous and subcutaneous administration exhibited nonlinearity. The pharmacodynamics of rh-EPO was analyzed using the maximum effect (E-max) and sigmoid maximum effect (sigmoid E-max) models. Both models involved the assumption that rh-EPO in plasma would stimulate the proliferation of erythroid progenitor cells. Akaike's information criterion for the E-max model was lower than that for the sigmoid E-max model, suggesting that the E-max model might be an optimal model. The rh-EPO concentration at which the effect is half of the maximum was 0.383 ng/ml. This pharmacodynamic analysis suggests that the maintenance of effective plasma concentration might be important for the efficacy of rh-EPO.