Acid metabolite of progabide pharmacokinetics following single administration in the rabbit with special references to HPLC and (3H) muscimol radioreceptor assay.
The aim of the present study was to monitor plasma levels of progabide and its metabolites in the rabbit following single oral administration of 20 mg.kg-1. The plasma levels were determined selectively using high performance liquid chromatography (HPLC) and then correlated with a global estimation by a (3H) muscimol radioreceptor assay (RRA). In our "in vitro" binding conditions progabide itself was virtually ineffective (IC50 greater than 100 microM) so only RRA active materiel plasma concentrations were studied. A good enough correlation (r = 0.71) has been established between HPLC and RRA plasma concentrations from 0 to 3 hours following oral administration specially considering the absorption phase. But with closed regards to the elimination pharmacokinetic parameters specially the elimination half-life values (t1/2el (RRA) = 1.67 h and t1/2el (HPLC) = 0.70 h) that correlation should be weaker than the former instead metabolites including GABAmide and GABA itself are probably present in amounts likely to affect the displacement of specific binding in the (3H) muscimol radioreceptor assay.
Brunet
C
C
Laboratoire de Pharmacologie et Pharmacocinétique, Faculté de Pharmacie, Lille, France.
Luyckx
M
M
Lhermitte
M
M
D000818:Animals; D001667:Binding, Competitive; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D005260:Female; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009118:Muscimol / Q000378:metabolism; D011817:Rabbits; D011869:Radioligand Assay; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D009118:Muscimol; C017985:progabide; D005680:gamma-Aminobutyric Acid