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http://dx.doi.org/10.4333/KPS.2009.39.5.373

Pharmacokinetic-Pharmacodynamic Modeling of a Direct Thrombin Inhibitor, Argatroban, in Rats  

Park, Eun-Hye (Korea Food & Drug Administration)
Shin, Beom-Soo (College of Pharmacy, Catholic University of Daegu)
Yun, Chi-Ho (Choongwae Pharm. Co.)
Lee, Mann-Hyung (College of Pharmacy, Catholic University of Daegu)
Yoo, Sun-Dong (College of Pharmacy, Sungkyunkwan University)
Publication Information
Journal of Pharmaceutical Investigation / v.39, no.5, 2009 , pp. 373-379 More about this Journal
Abstract
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.
Keywords
Argatroban; Pharmacokinetics; Pharmacodynamics; Thrombin time; Activated partial thromboplastin time;
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