On the Relationship Between Plasma Concentrations of Drugs and Outcome of Stroke Studies in Laboratory Animals

: In assessing plasma concentrations of drugs in relation to neuroprotective effect, emphasis should be placed on measured or calculated concentrations during the window of opportunity for effect, rather than at the end of the experiment. Unbound (plasma free) concentrations should be especially con...

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Veröffentlicht in:Annals of the New York Academy of Sciences 2001-06, Vol.939 (1), p.297-308
1. Verfasser: CURRY, STEPHEN H.
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container_title Annals of the New York Academy of Sciences
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creator CURRY, STEPHEN H.
description : In assessing plasma concentrations of drugs in relation to neuroprotective effect, emphasis should be placed on measured or calculated concentrations during the window of opportunity for effect, rather than at the end of the experiment. Unbound (plasma free) concentrations should be especially considered as should brain penetration to the stroked area. Problem‐solving exercises should include post hoc assessment of dosing residues and proof of exposure. The shape of the graph of response versus concentration in plasma is very steep, giving the impression of an all‐or‐none effect. Although higher doses lead to greater effects, attempts to statistically correlate plasma level and infarct size are likely to be unsuccessful. There is strong evidence that the pharmacokinetic properties of drugs are affected by the physiological consequences of ischemia.
doi_str_mv 10.1111/j.1749-6632.2001.tb03637.x
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subjects Animals
Area Under Curve
Brain - metabolism
Callithrix
Cats
Excitatory Amino Acid Antagonists - blood
Excitatory Amino Acid Antagonists - pharmacokinetics
Gerbillinae
Humans
Infarction, Middle Cerebral Artery - blood
Laboratory animals
Models, Animal
Neuroprotective Agents - blood
Neuroprotective Agents - pharmacokinetics
Pharmacokinetics
Plasma concentration
Pyridines - blood
Pyridines - pharmacokinetics
Rats
Species Specificity
Stroke studies
title On the Relationship Between Plasma Concentrations of Drugs and Outcome of Stroke Studies in Laboratory Animals
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