CLC number: R969.1
On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 0000-00-00
Cited: 1
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Han Guo-Zhu, Ren Hong-Can, Lu Yong, Li Ying, Xiao Shu, Ye Hong-Wei, Wang He-Mu. Pharmacokinetic study with N-Ile1-Thr2-63-desulfato-r-hirudin in rabbits by means of bioassay[J]. Journal of Zhejiang University Science B, 2006, 7(3): 241-244.
@article{title="Pharmacokinetic study with N-Ile1-Thr2-63-desulfato-r-hirudin in rabbits by means of bioassay",
author="Han Guo-Zhu, Ren Hong-Can, Lu Yong, Li Ying, Xiao Shu, Ye Hong-Wei, Wang He-Mu",
journal="Journal of Zhejiang University Science B",
volume="7",
number="3",
pages="241-244",
year="2006",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.2006.B0241"
}
%0 Journal Article
%T Pharmacokinetic study with N-Ile1-Thr2-63-desulfato-r-hirudin in rabbits by means of bioassay
%A Han Guo-Zhu
%A Ren Hong-Can
%A Lu Yong
%A Li Ying
%A Xiao Shu
%A Ye Hong-Wei
%A Wang He-Mu
%J Journal of Zhejiang University SCIENCE B
%V 7
%N 3
%P 241-244
%@ 1673-1581
%D 2006
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.2006.B0241
TY - JOUR
T1 - Pharmacokinetic study with N-Ile1-Thr2-63-desulfato-r-hirudin in rabbits by means of bioassay
A1 - Han Guo-Zhu
A1 - Ren Hong-Can
A1 - Lu Yong
A1 - Li Ying
A1 - Xiao Shu
A1 - Ye Hong-Wei
A1 - Wang He-Mu
J0 - Journal of Zhejiang University Science B
VL - 7
IS - 3
SP - 241
EP - 244
%@ 1673-1581
Y1 - 2006
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.2006.B0241
Abstract: Aim: To study the pharmacokinetic (PK) properties in rabbits treated with N-Ile1-Thr2-63-desulfato-r-hirudin (rH) newly developed in China by means of bioassay in order to provide preclinical experiment basis for its development as a novel anticoagulant agent. Methods: rH plasma concentration was determined using bioassay based on ex vivo antithrombin activity of rH. Normal rabbits received iv rH 4.0, 2.0 and 1.0 mg/kg or sc rH 2.0 mg/kg, respectively. The rabbits with acute severe renal failure were given iv rH 2.0 mg/kg. Results: The bioassay described in this paper met requirements for study of PK in rabbits. The major PK parameters after iv dosing were as follows: t1/2β 58.4~59 min. Vd 0.09~0.12 L/kg, CL 0.0035~0.0040 L/(kg∙min); AUC were proportional to the doses, t1/2 and CL did not change significantly with the doses. The sc bioavailability reached 94%. The rabbits suffering from acute severe renal failure presented 11-fold longer t1/2β and 13-fold greater AUC than normal healthy rabbits. Conclusion: rH exhibited rapid elimination, distribution was only limited to extracellular space and good absorption from sc site. The excretion of rH by kidneys played a very important role in the elimination of rH. The PK of rH could be described by the two- and one-compartment model after iv and sc dosing, respectively, and followed linear kinetics.
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