Pharmacokinetic study with N-Ile1-Thr2-63-desulfato-r-hirudin in rabbits by means of bioassay.
J Zhejiang Univ Sci B
; 7(3): 241-4, 2006 Mar.
Article
en En
| MEDLINE
| ID: mdl-16502513
ABSTRACT
AIM:
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.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 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.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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tiempo de Trombina
/
Bioensayo
/
Algoritmos
/
Hirudinas
/
Modelos Biológicos
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Zhejiang Univ Sci B
Asunto de la revista:
BIOLOGIA
/
MEDICINA
Año:
2006
Tipo del documento:
Article
País de afiliación:
China