Pharmacokinetics and Tolerability Evaluation of Human Coagulation Recombinant Factor VIII ($GreenGene^{TM}$) in Hemophilia A Patients

혈우병 A형 환자에서 재조합 혈액응고인자 VIII (그린진주$^{TM}$)의 내약성 및 약동학적 특성에 관한 연구

Background: $GreenGene^{TM}$ (Green Cross Corp.) is a recombinant clotting factor VIII which is used for hemophilia A. This study aimed to investigate the pharmacokinetics and safety profiles of 25 IU/kg and 50 IU/kg of $GreenGene^{TM}$ in Korean hemophilia A patients. Methods: A dose-block randomized, single-blind, active drug-controlled, single and multiple dose, parallel-group study was conducted with 16 hemophilia A patients (25 IU/kg: 50 IU/kg = 8:8). They received $GreenGene^{TM}$ or $GreenMono^{TM}$(active control) intravenously on day 1 and every other day from day 4 to 10. FVIII:C (Factor VIII procoagulant activity) was measured to determine the pharmacokinetics (PK) at baseline and up to 48 hours for single and multiple administration. PK parameters were determined using noncompartmental methods. Results: The maximum concentration ($C_{max}$) and the area under the concentration-time curve ($AUC_{0-48}$) of the $GreenGene^{TM}$ 25 IU/kg ($mean{\pm}SD$) were $59.00{\pm}19.26$ % and $774.40{\pm}380.13%{\cdot}h$ respectively, while those of 50 IU/kg were $131.50{\pm}39.81$ % and $1462.44{\pm}397.09%{\cdot}h$ after single administration. The $C_{max}$ and $AUC_{0-48}$ in steady state of the $GreenGene^{TM}$ 25 IU/kg were $68.17{\pm}22.75$ % and $863.30{\pm}334.40%{\cdot}h$, while those of 50 IU/kg were $147.17{\pm}18.47$ % and $1820.08{\pm}704.42%{\cdot}h$. No serious adverse event was observed. Conclusion: The $GreenGene^{TM}$ to hemophilia A patients appeared to be well tolerated within range of 25-50 IU/kg. The PK parameters of factor VIII showed dose-independent manner with 25 IU/kg and 50 IU/kg dose ranges.