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 administra tion exhibited nonlinearity. The pharmaco dynamics 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 con centration might be important for the efficacy of rh-EPO.