The authors monitored the plasma levels of clobazam (CLO) and its principal metabolite, N-desmethylclobazam (NCLO) during chronic treatment of more than 400 epileptic patients receiving different co-medications, such as phenytoin (PH), carbamazepine (CBZ), sodium valproate (VPA) and phenobarbital (PB). This study investigated the influence of age and antiepileptic drugs on plasma levels of CLO and NCLO. Plasma concentrations measured 3 hr after morning administration of CLO varied from 30 to 700 [formula; see text] for CLO, and from 160 to 7000 [formula; see text] for NCLO. Plasma levels of CLO were higher in patients aged 20-30 years. NCLO concentrations increased with age up to 20 years. Coadministered antiepileptic compounds significantly decreased maximal plasma levels of CLO. Moreover, PH and CBZ a significantly increased the plasma levels of NCLO. Results on the influence of CBZ on CLO kinetics were confirmed in a group of ten patients receiving PB and VPA and later PB, VPA and CBZ as CLO associated drugs. The influence of VPA on the pharmacokinetics parameters of CLO was also evaluated in a patient in the latter group.
RÉSUMÉ
Plusieurs études récentes attirent l'attention sur la diversité des formes que pouvait prendre la tenure seigneuriale tout en affirmant son caractère essentiellement féodal. Mais la seigneurie laïque, plus sensible aux considérations familiales, demeure presque inconnue. Cette étude confirme la flexibilité de la tenure seigneuriale en démontrant son adaptation à l'exploitation forestière. Elle démontre en plus l'importance de la situation personnelle du seigneur et des pratiques de gestion dans les relations seigneur-censitaires, dont les points tournants suivent la conjoncture socio-économique : la migration loyaliste, la fin des guerres napoléoniennes, la défaite des Rébellions. On observe aussi l'importance des liens familiaux dans l'exercice du patronage seigneurial. Il se peut que l'étude des seules seigneuries ecclésiastiques ait dissimulé un facteur important du dynamisme social de la seigneurie — la famille seigneuriale.
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