Pharmacokinetic study with N-Ile1-Thr2-63-desulfato-r-hirudin in rabbits by means of bioassay / 浙江大学学报(英文版)(B辑:生物医学和生物技术)
Journal of Zhejiang University. Science. B
;
(12): 241-244, 2006.
Article
in English
| WPRIM
| ID: wpr-251931
ABSTRACT
<p><b>AIM</b>To study the pharmacokinetic (PK) properties in rabbits treated with N-Ile(1)-Thr(2)-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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>The bioassay described in this paper met requirements for study of PK in rabbits. The major PK parameters after iv dosing were as follows t(1/2beta) 58.4-59 min. V(d) 0.09-0.12 L/kg, CL 0.0035-0.0040 L/(kg.min); AUC were proportional to the doses, t(1/2) 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 t(1/2beta) and 13-fold greater AUC than normal healthy rabbits.</p><p><b>CONCLUSION</b>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.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Thrombin Time
/
Biological Assay
/
Blood
/
Algorithms
/
Computer Simulation
/
Pharmacokinetics
/
Metabolic Clearance Rate
/
Reproducibility of Results
/
Sensitivity and Specificity
/
Hirudins
Type of study:
Diagnostic study
/
Prognostic study
Limits:
Animals
Language:
English
Journal:
Journal of Zhejiang University. Science. B
Year:
2006
Type:
Article
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