rHuEPO plays a central role as chemicals for the treatment of many diseases. Due to its short half-life, the main aim for this pharmacokinetic study is to investigate a newly developed PEG-rHuEPO with large molecular weight in SD rats. After a single intramuscular administration of different doses of 125I-PEG-rHuEPO, pharmacokinetic parameters, tissue distribution, and excretion were analyzed. In in vivo half-life time measured after 125I-PEG-rHuEPO administration at the doses of 1, 2, and 3？ g/kg, 1/2 was 1.90, 1.19, and 2.50 hours, respectively, whereas 1/2 was 22.37, 26.21, and 20.92 hours, respectively; at 8, 24, and 48 hours after intramuscular administration, PEG-rHuEPO was distributed to all of the examined tissues, however, with high concentrations of radioactivity, only in plasma, blood, muscle at the administration site, and bone marrow. Following a 2？ g/kg single intramuscular administration, approximately 21% of the radiolabeled dose was recovered after almost seven days of study. Urine was the major route of excretion; 20% of the administered dose was recovered in the urine, while excretion in the feces was less than 1.4%. Therefore, this PEG-rHuEPO has potential to be clinically used and could reduce frequency of injection. 1. Introduction Erythropoiesis, the formation of red blood cells from multipotent stem cells in the bone marrow, is an exquisitely regulated process in which the glycoprotein hormone erythropoietin (EPO), which is primarily produced in either adult kidney or fetal liver [1], plays a role [2] as the major humoral regulator of red cell production [3]. This functional pleiotropy of EPO has led to its clinical use for the treatment of several diseases [4–6]. Although obviously time is required to understand some parts of the mechanism, with revelations of novel physiological functions and tissue-specific regulation clearly, there are likely to be more surprises in clinical usage of recombinant human erythropoietin (rHuEPO) along the way [7]. Not surprisingly, rHuEPO is amongst the top selling pharmaceutical products worldwide [7]. The first commercial product epoetin has a plasma half-life of only 6–8？h [7] in humans. The second-generation erythropoietic agent [8] has an approximately 3-fold longer plasma half-life, as long as the third-generation, which has been investigated in phase II [9] clinical trials. Another new erythropoietin derivative with successfully prolonged half-life has been reported recently [10]. However, rHuEPO must be administered relatively frequently, in general 3 times a week either intravenously or
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