The pharmacokinetics of fenfluramine enantiomers were studied in normal volunteers following the administration of single of multiple doses of racemic fenfluramine hydrochloride. Plasma concentrations and half-lives were similar for both enantiomers after single 40 mg of 60 mg doses. However following chronic administration (2 x 40 mg for 10 days), significant differences were observed between the kinetic parameters of the two enantiomers, the l-form of fenfluramine and norfenfluramine accumulating in plasms more than the d-forms.
1. Rats were treated with d-, l-or dl-fenfluramine. The two optical isomers and their metabolites were determined in plasma, red blood cells and brain areas such as striatum and brainstem. 2. In all cases, the levels of d-fenfluramine were higher than those of the l-enantiomer, while levels of the metabolite norfenfluramine were lower for the d- than the l-form. 3. When metabolism of fenfluramine was inhibited by pre-treatment with SKF 525-A, the concentrations of the enantiomers no longer differed.
Résumé L’incitation à la collaboration est profondément inscrite dans les injonctions. Cherchant à explorer les modalités d’action que les enseignants développent dans leur dynamique collective de travail, nous avons mené une recherche à partir du dispositif « maître surnuméraire » des Hauts-de-Seine. Nos analyses sociologiques plurielles montrent que le travail conjoint émerge dans des conditions socio-historiques particulières. Il se structure à partir d’une mise en relation des pratiques et conduit à une offre pédagogique orientée par la différenciation pour laquelle les enseignants développent une polyvalence de rôles.
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