John Libbey Eurotext

Journal de Pharmacie Clinique

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Chronopharmacokinetics of carbamazepin and 10,11 epoxide Volume 17, issue 3, Septembre 1998

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  • Key words: carbamazepine, carbamazepine-10,11-epoxide, chronopharmacokinetics, saliva/plasma ratio.
  • Page(s) : 153-6
  • Published in: 1998

A diurnal variation study of carbamazepine (CBZ) and its metabolite carbamazepine-10,11-epoxide (EPOX) was carried out on six healthy volunteers, measuring drug levels in plasma and saliva throughout 34 hours. Four hundred milligrams of CBZ were given to subjects at 8:00 am or 8:00 pm, in a two-way crossover design. Drug and metabolite concentration in plasma and saliva stimulated with parafilm (after 24 hours post-dose) were higher during the night. The EPOX/CBZ metabolic ratio did not show any change between dark and light periods. The non-stimulated saliva/plasma concentration ratio (S/P) was higher during the day, but this quotient did not change when stimulated saliva was considered. Diurnal variation in the body blood flow seems to be a reasonable explanation for those differences. Factors such as protein binding or metabolic pathway are discarded as sources of carbamazepine chronopharmacokinetic variations.