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Mathematical modeling of pharmacokin...
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Lee, Yung-Jin.
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Mathematical modeling of pharmacokinetics and pharmacodynamics with a nonlinear drug-plasma protein binding model.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Mathematical modeling of pharmacokinetics and pharmacodynamics with a nonlinear drug-plasma protein binding model./
作者:
Lee, Yung-Jin.
出版者:
Ann Arbor : ProQuest Dissertations & Theses, : 1994,
面頁冊數:
260 p.
附註:
Source: Dissertation Abstracts International, Volume: 55-02, Section: B, page: 3790.
Contained By:
Dissertation Abstracts International55-02B.
標題:
Pharmacology. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=9418926
Mathematical modeling of pharmacokinetics and pharmacodynamics with a nonlinear drug-plasma protein binding model.
Lee, Yung-Jin.
Mathematical modeling of pharmacokinetics and pharmacodynamics with a nonlinear drug-plasma protein binding model.
- Ann Arbor : ProQuest Dissertations & Theses, 1994 - 260 p.
Source: Dissertation Abstracts International, Volume: 55-02, Section: B, page: 3790.
Thesis (Ph.D.)--The University of Oklahoma Health Sciences Center, 1994.
The present study attempted to propose a PK-PD model, including a drug-plasma protein binding model, for a highly protein bound drug.Subjects--Topical Terms:
634543
Pharmacology.
Mathematical modeling of pharmacokinetics and pharmacodynamics with a nonlinear drug-plasma protein binding model.
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Thesis (Ph.D.)--The University of Oklahoma Health Sciences Center, 1994.
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The present study attempted to propose a PK-PD model, including a drug-plasma protein binding model, for a highly protein bound drug.
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A drug-plasma protein binding model was proposed and tested with ceftriaxone-cefotaxime in vitro and in vivo drug-plasma binding data in rats. The results were comparable to previous reports. Therefore, the in vivo drug-plasma protein competitive binding model was validated. The model was applied further to the tolbutamide (TBM)-sulfadimethoxine (SDM) in vivo drug-plasma protein interaction to evaluate the change in pharmacological effects of TBM caused by coadministration of different SDM doses.
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The experimental assay methods used in this study including the in vitro and the in vivo study were developed. These included TBM and SDM HPLC assays, insulin RIA method and blood glucose assay. The results suggested that these assay methods be reliable and accurate enough to be used for this study.
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The in vitro and in vivo TBM and SDM drug-plasma protein binding data in rabbits were analyzed to determine PK and PD parameters to validate the proposed model. The results obtained from the in vitro data suggests that, although SDM has a lower association constant than TBM, SDM still can compete with TBM for plasma protein binding. The parameters from the in vitro study were used as initial values for the in vivo data fitting. The results obtained from the in vivo study provided pharmacokinetic parameters for both model drugs that were comparable to those found in the in vitro study, as well as those previously reported. Some of TBM pharmacodynamic parameters for both insulin release and blood glucose concentration lowering are reported for first time in the present study. The observed data were well described by the proposed model.
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In conclusion, a mathematical PK-PD model including drug-protein plasma binding has been successfully proposed and proved to be useful in the analysis of the results obtained in the present study.
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