Mechanism for the nonlinear pharmacokinetics of erythropoietin in rats.

  title={Mechanism for the nonlinear pharmacokinetics of erythropoietin in rats.},
  author={Masatomo Kato and Hironaga Kamiyama and Arimichi Okazaki and Kunio Kumaki and Yukio Kato and Yuichi Sugiyama},
  journal={The Journal of pharmacology and experimental therapeutics},
  volume={283 2},
The contribution of erythropoietin- (EPO) receptors in target tissues, such as bone marrow and spleen, to the nonlinear pharmacokinetics of recombinant human EPO (rh-EPO) was evaluated in rats. The total body clearance after i.v. administration of rh-EPO (0.2-5 microg/kg) decreased as the dose of rh-EPO increased, approaching a plateau at high doses. The uptake clearance of 125I-rh-EPO by the target tissues, bone marrow and spleen, exhibited clear saturation. The Km values ranged from 240 to… CONTINUE READING