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KMID : 0369820090390050373
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Jorunal of Korean Pharmaceutical Sciences
2009 Volume.39 No. 5 p.373 ~ p.379
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Pharmacokinetic-Pharmacodynamic Modeling of a Direct Thrombin Inhibitor, Argatroban, in Rats
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Park Eun-Hye
Shin Beom-Soo
Lee Mann-Hyung
Yoo Sun-Dong
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Abstract
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This study was conducted to develop a pharmacokinetic-pharmacodynamic (PK/PD) model of a direct thrombin inhibitor, argatroban to predict the concentration-effect profiles in rats. Argatroban was i.v. injected to rats at 0. 2, 0.8 and 3.2 mg/kg doses (n = 4-5 per dose), and plasma drug levels were determined by a validated LC/MS/MS assay. The pharmacokinetics of argatroban was linear over the i.v. dose range studied. The thrombin time (TT) and the activated partial thromboplastin time (aPTT) were measured in rat plasma and they were found to linearly increase with increasing the dose. A 2-compartment pharmacokinetic model linked with an indirect response pharmacodynamic model was successfully utilized to evaluate the drug concentration-response relationship.
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KEYWORD
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Argatroban, Pharmacokinetics, Pharmacodynamics, Thrombin time, Activated partial thromboplastin time
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