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

Abstract

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.