Influence of the rate of intravenous administration of eliprodil (SL 82.0715), a new anti-ischaemic agent, on its distribution in rat plasma and tissues.
This investigation studied the possible effect of different iv administration rates (bolus and infusions) of eliprodil, a new anti-ischemic agent, on the drug distribution in various body compartments. Following bolus administration of a 15-mg kg-1 dose, plasma concentrations were best fitted by a 3-compartment open model of t1/2 alpha = 14 sec, t1/2 beta = 4 min, and t1/2 gamma = 1.8 hr. Plasma and heart Cmax values were lowered by decreasing the infusion rate (the 15-mg dose was administered in 15 or 60 min) whereas brain Cmax values were not modified. In contrast, AUC values did not depend upon the rate of infusion. The present findings may have important implications in relating tissue concentrations with the desired therapeutic effect as well as with the side effects of the drug at its sites of action within brain and heart. The use of a simplified model built with plasma and tissue kinetic parameters following bolus injection allows one to predict the amount of drug present in the organs according to the mode of administration, but not the evolution of tissue to plasma ratio during the infusions.
Garrigou-Gadenne
D
D
Synthelabo-Recherche (L.E.R.S.), Developpement Chimique et Pharmaceutique, Pharmacocinetique et Métabolisme, Chilly-Mazarin, France.
Thenot
J P
JP
Morselli
P L
PL
D000818:Animals; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D010880:Piperidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; C058083:eliprodil