Liu Yu-Bin1 Wang Mei-Xia2 Dong Xiao-Na1 He-Jia3 Zhang Lin1 Zhou
Ying1 Xia-Xia3 Dou Gui-Fang1 Wu Chu-tse1* Jin Ji-De1*
1 Beijing Institute of Radiation
Medicine,Beijing 100850,China
2 Beijing You’an Hospital, Capital Medical University, Beijing
100069,China
3 Beijing SH Biotechnology Co., Ltd., Beijing 100093,China
* Corresponding author,Wu Chu-tse E⁃mail:wuct@bmi.ac.cn ; Jin
Ji-De E⁃mail:jinjide505@163. com
Keywords:Clinical Trials, Patient safety, Drug metabolism,
Anticoagulants
AIMS: The aims of the study were to evaluate the tolerability,
safety and pharmacokinetics of single and continuous administration of
recombinant neorudin (EPR-hirudin, EH) by intravenous injection in
healthy subjects, and to provide a safe dosage range for phase II
clinical research.
METHODS: A single and continuous administration dose phase I
clinical study was conducted.
Forty-four subjects were received EH
as single-dose of 0.2-2.0 mg/kg by intravenous bolus plus drip; Eighteen
healthy subjects were randomly divided into 3 dose groups (0.15-0.45
mg/kg/h) with 6 cases in each group in the continuous administration
trial.
RESULTS: Single or continuous doses of neorudin were generally
well tolerated in healthy adult subjects. There were no serious adverse
events (SAEs), and all adverse events (AEs) were mild to moderate. No
subjects withdrew from the trial due to adverse events. There were no
clinically relevant changes in physical examination, clinical chemistry,
urinalysis or vital signs. The incidence of adverse events was not
significantly related to the dose and systemic exposure. After the
single-dose and continuous administration, the serum EH concentration
reached a peak at 0.083h,the exposure increased with the increase of
the administered dose with the mean half-life (T1/2)
ranging from 1.7 to 2.5h, the clearance (Cl) ranging from 123.9 to179.7
mL/h/kg, and the apparent volume of
distribution (Vd) ranging from 402.7 to 615.2 mL/kg.
CONCLUSIONS :The safety, tolerability and pharmacokinetics characteristics of EH can
be used to guide rational drug dosing and choose therapeutic regimens in
subsequent clinical studies.