Exploration of the Effect and Pharmacokinetics of Intracvenous and Subcutaneous GC1113, a Novel Erythropoiesis-Stimulating Agent
새로운 적혈구생성 촉진제 GC1113의 정맥 또는 피하 투여시의 효과와 약동학적 특성에 대한 탐색 연구

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의과대학 협동과정임상약리학전공
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서울대학교 대학원
pharmacokineticspharmacodynamicserythropoiesishealthy volunteers
학위논문 (석사)-- 서울대학교 대학원 : 협동과정임상약리학전공, 2014. 2. 신상구.
Introduction: GC1113, a hybrid Fc fused erythropoietin, is a novel erythropoiesis-stimulating agent which is expected to have an extended duration of action. The preclinical data showed that the hemoglobin increase lasted longer following GC1113 administration than it did following the administration of NESP®(Darbepoetin alfa). This study aimed to investigate the pharmacodynamic (PD), pharmacokinetic (PK) characteristics and tolerability profiles of GC1113 in humans after single intravenous (IV) or subcutaneous (SC) administration and to compare the results with those for NESP®.
Methods: A dose-block randomized, placebo- and active- controlled, dose-escalation, phase 1 clinical trial was conducted with 96 healthy volunteers. Blood samples were collected before and up to 672 hours after drug administration and the erythropoietin concentration following the GC1113 or NESP® administration was measured by an enzyme-linked immunosorbent assay (ELISA). PK and PD parameters were determined using noncompartmental methods. Tolerability including immunogenicity evaluation was monitored during hospitalization and until the end of the study.
Results: The reticulocyte count-time profiles in the IV GC1113 3–5 μg/kg groups were comparable with those of the NESP® 30 μg. After subcutaneous administration of GC1113, reticulocyte count peaked later and decreased more slowly than it did following NESP® administration. For pharmacokinetics, GC1113 showed faster elimination and slower absorption through subcutaneous administration than NESP®. The GC1113 (0.3–5 μg/kg for IV, 1–8 μg/kg SC) was well tolerated in the volunteers, and no immunogenicity was observed.
Conclusions: GC1113 showed erythropoietic activity in healthy volunteers. Intravenous GC1113 showed comparable erythropoietic activity to NESP®, and following subcutaneous administration, the reticulocyte count increase lasted longer for GC1113 than for NESP®. GC1113 was tolerated and effective in the studied dose range
these findings could be applied to further clinical studies with patients.
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College of Medicine/School of Medicine (의과대학/대학원)Program in Clinical Pharmacology (협동과정-임상약리학전공)Theses (Master's Degree_협동과정-임상약리학전공)
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