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INFLUENCE OF PLASMA PROTEIN BINDING ON PHARMACOKINETICS AND PHARMACODYNAMICS OF DRUGS.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	INFLUENCE OF PLASMA PROTEIN BINDING ON PHARMACOKINETICS AND PHARMACODYNAMICS OF DRUGS./
作者:	HUANG, JIN-DING.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 1982,
面頁冊數:	212 p.
附註:	Source: Dissertations Abstracts International, Volume: 43-07, Section: B.
Contained By:	Dissertations Abstracts International43-07B.
標題:	Pharmaceuticals. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=8310960
ISBN:	9798662354937

INFLUENCE OF PLASMA PROTEIN BINDING ON PHARMACOKINETICS AND PHARMACODYNAMICS OF DRUGS.
HUANG, JIN-DING.

INFLUENCE OF PLASMA PROTEIN BINDING ON PHARMACOKINETICS AND PHARMACODYNAMICS OF DRUGS. - Ann Arbor : ProQuest Dissertations & Theses, 1982 - 212 p.

Source: Dissertations Abstracts International, Volume: 43-07, Section: B.

Thesis (Ph.D.)--University of California, San Francisco, 1982.

This item must not be sold to any third party vendors.

The influence of altered serum protein binding on the disposition of disopyramide and the pharmacological response to the drug ((DELTA)QRS duration) was studied in the rabbit. Binding changes of disopyramide were achieved by injection of human glycoprotein fraction VI. The total concentration-response relationship of RS-disopyramide was found to be different between the glycoprotein-treated rabbits and control rabbits. The unbound concentration-response relationship, on the other hand, was the same. During constant infusion of R-disopyramide, the glycoprotein injection increased the total drug concentration in serum at steady state while the unbound concentration was unaltered. The glycoprotein injection, however, decreased the unbound concentration and increased the total concentration during the steady-state infusion of S-disopyramide. In both experiments, the (DELTA)QRS duration reflected the change in the unbound drug concentration and not in the total concentration. For a drug with concentration-dependent serum protein binding, the unbound fraction of drug decreases during the drug elimination process. The clearance of the drug at a given blood flow is lower than would be expected from the observed unbound fraction in venous blood from a noneliminating organ. Simulations showed that consideration of concentration-dependent binding during drug elimination process is important when the intrinsic clearance is higher than the blood flow and when the unbound drug concentration is much greater than the dissociation equilibrium constant of the binding complex. The effect of serum protein binding on the clearance of a medium-to-high extraction ratio drug, S-disopyramide, was studied in individual rabbits by successive injections of increasing doses of human glycoprotein. The results are consistent with predictions based on both the "well-stirred" and "parallel tube" models. However, the variation was too large to determine accurately the clearance-drug binding relationship.

ISBN: 9798662354937Subjects--Topical Terms:

3562593
Pharmaceuticals.

INFLUENCE OF PLASMA PROTEIN BINDING ON PHARMACOKINETICS AND PHARMACODYNAMICS OF DRUGS.
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500 $a Source: Dissertations Abstracts International, Volume: 43-07, Section: B.
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506 $a This item must not be added to any third party search indexes.
520 $a The influence of altered serum protein binding on the disposition of disopyramide and the pharmacological response to the drug ((DELTA)QRS duration) was studied in the rabbit. Binding changes of disopyramide were achieved by injection of human glycoprotein fraction VI. The total concentration-response relationship of RS-disopyramide was found to be different between the glycoprotein-treated rabbits and control rabbits. The unbound concentration-response relationship, on the other hand, was the same. During constant infusion of R-disopyramide, the glycoprotein injection increased the total drug concentration in serum at steady state while the unbound concentration was unaltered. The glycoprotein injection, however, decreased the unbound concentration and increased the total concentration during the steady-state infusion of S-disopyramide. In both experiments, the (DELTA)QRS duration reflected the change in the unbound drug concentration and not in the total concentration. For a drug with concentration-dependent serum protein binding, the unbound fraction of drug decreases during the drug elimination process. The clearance of the drug at a given blood flow is lower than would be expected from the observed unbound fraction in venous blood from a noneliminating organ. Simulations showed that consideration of concentration-dependent binding during drug elimination process is important when the intrinsic clearance is higher than the blood flow and when the unbound drug concentration is much greater than the dissociation equilibrium constant of the binding complex. The effect of serum protein binding on the clearance of a medium-to-high extraction ratio drug, S-disopyramide, was studied in individual rabbits by successive injections of increasing doses of human glycoprotein. The results are consistent with predictions based on both the "well-stirred" and "parallel tube" models. However, the variation was too large to determine accurately the clearance-drug binding relationship.
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