PMID- 33957018
OWN - NLM
STAT- MEDLINE
DCOM- 20220131
LR  - 20220131
IS  - 2052-1707 (Electronic)
IS  - 2052-1707 (Linking)
VI  - 9
IP  - 3
DP  - 2021 May
TI  - A phase I, single and continuous dose administration study on the safety, 
      tolerability, and pharmacokinetics of neorudin, a novel recombinant anticoagulant 
      protein, in healthy subjects.
PG  - e00785
LID - 10.1002/prp2.785 [doi]
LID - e00785
AB  - The aim of this study was to evaluate the tolerability, safety, and 
      pharmacokinetics of single and continuous dose administration of recombinant 
      neorudin (EPR-hirudin, EH) by intravenous administration in healthy subjects, and 
      to provide a safe dosage range for phase II clinical research. Forty-four 
      subjects received EH as a single dose of between 0.2 and 2.0 mg/kg by intravenous 
      bolus and drip infusion. In addition, 18 healthy subjects were randomly divided 
      into three dose groups (0.15, 0.30, and 0.45 mg/kg/h) with 6 subjects in each 
      group for the continuous administration trial. Single or continuous doses of 
      neorudin were generally well tolerated by healthy adult subjects. There were no 
      serious adverse events (SAEs), and all adverse events (AEs) were mild to 
      moderate. Moreover, no subjects withdrew from the trial because of AEs. There 
      were no clinically relevant changes in physical examination results, clinical 
      chemistry, urinalysis, or vital signs. The incidence of adverse events was not 
      significantly related to drug dose or systemic exposure. After single-dose and 
      continuous administration, the serum EH concentration reached its peak at 5 min, 
      and the exposure increased with the increase in the administered dose. The mean 
      half-life (T(1/2) ), clearance (Cl), and apparent volume of distribution (Vd) of 
      EH ranged from 1.7 to 2.5 h, 123.9 to 179.7 ml/h/kg, and 402.7 to 615.2 ml/kg, 
      respectively. The demonstrated safety, tolerability, and pharmacokinetic 
      characteristics of EH can be used to guide rational drug dosing and choose 
      therapeutic regimens in subsequent clinical studies. Clinical trial registration: 
      Chinadrugtrials.org identifier: CTR20160444.
CI  - (c) 2021 The Authors. Pharmacology Research & Perspectives published by John Wiley 
      & Sons Ltd, British Pharmacological Society and American Society for Pharmacology 
      and Experimental Therapeutics.
FAU - Liu, Yubin
AU  - Liu Y
AUID- ORCID: 0000-0001-9479-8727
AD  - Beijing Institute of Radiation Medicine, Beijing, China.
FAU - Wang, Meixia
AU  - Wang M
AD  - Phase 1 Clinical Research Center, Beijing You'an Hospital, Capital Medical 
      University, Beijing, China.
FAU - Dong, Xiaona
AU  - Dong X
AD  - Beijing Institute of Radiation Medicine, Beijing, China.
FAU - He, Jia
AU  - He J
AD  - Beijing SH Biotechnology Co., Ltd., Beijing, China.
FAU - Zhang, Lin
AU  - Zhang L
AD  - Beijing Institute of Radiation Medicine, Beijing, China.
FAU - Zhou, Ying
AU  - Zhou Y
AD  - Beijing Institute of Radiation Medicine, Beijing, China.
FAU - Xia, Xia
AU  - Xia X
AD  - Beijing SH Biotechnology Co., Ltd., Beijing, China.
FAU - Dou, Guifang
AU  - Dou G
AD  - Beijing Institute of Radiation Medicine, Beijing, China.
FAU - Wu, Chu-Tse
AU  - Wu CT
AD  - Beijing Institute of Radiation Medicine, Beijing, China.
FAU - Jin, Jide
AU  - Jin J
AD  - Beijing Institute of Radiation Medicine, Beijing, China.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pharmacol Res Perspect
JT  - Pharmacology research & perspectives
JID - 101626369
RN  - 0 (Anticoagulants)
RN  - 0 (Hirudins)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
MH  - Adult
MH  - Anticoagulants/*administration & dosage/blood/pharmacokinetics/urine
MH  - Female
MH  - Healthy Volunteers
MH  - Hirudins/*administration & dosage/blood/pharmacokinetics/urine
MH  - Humans
MH  - Male
MH  - Recombinant Fusion Proteins/*administration & dosage/blood/pharmacokinetics/urine
MH  - Young Adult
PMC - PMC8101608
OTO - NOTNLM
OT  - clinical pharmacology
OT  - in vivo
OT  - pharmacokinetics
OT  - safety pharmacology
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this study.
EDAT- 2021/05/07 06:00
MHDA- 2022/02/01 06:00
PMCR- 2021/05/06
CRDT- 2021/05/06 18:19
PHST- 2021/04/01 00:00 [revised]
PHST- 2021/03/17 00:00 [received]
PHST- 2021/04/08 00:00 [accepted]
PHST- 2021/05/06 18:19 [entrez]
PHST- 2021/05/07 06:00 [pubmed]
PHST- 2022/02/01 06:00 [medline]
PHST- 2021/05/06 00:00 [pmc-release]
AID - PRP2785 [pii]
AID - 10.1002/prp2.785 [doi]
PST - ppublish
SO  - Pharmacol Res Perspect. 2021 May;9(3):e00785. doi: 10.1002/prp2.785.