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Circadian effect on carbamazepine kinetics in rat

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Summary

The purpose of the present study was to investigate whether the time of day (24 h) at which carbamazepine is administered influences its pharmacokinetics in the rat. The pharmacokinetics of a single, 100 mg.kg−1 bodyweightper os, dose of carbamazepine were studied at four different fixed time points of a 24-hour period (i.e. 10.00, 16.00, 22.00 or 04.00 h) in Wistar AF-SPF adult male rats maintained under controled environmental conditions (LD: 18.00 – 06.00h) during October 1978. The total plasma levels and the unbound fraction were measured according to an immunoenzymatic method (EMIT). The effects of fasting were also investigated.

The data shows circadian variations of pharmacokinetic parameters: the maximum peak concentration and the maximum time to reach this peak was observed when the drug was given respectively at 16.00h and at 10.00h. The elimination half-life varied from 15.15 hours at I6.00h to 10.48 hours at 22.00h. The observed variations may be related to: daily fluctuations of absorption or binding of the drug; diurnal variations of the hepatic drug metabolizing enzymes responsible for the inactivation; and/or diurnal variations in excretion rate of the drug.

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Authors and Affiliations

  1. Laboratory of Medical Pharmacology, University of Aix-Marseille II, F-13385, Marseille Cedex 5, France

    B. Bruguerolle, M. Valli, L. Bouyard, G. Jadot & P. Bouyard

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  1. B. Bruguerolle
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  2. M. Valli
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  3. L. Bouyard
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  4. G. Jadot
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  5. P. Bouyard
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This work is dedicated to Prof. H. Gastaut for his accession to the Honorary-Chairmanship of the Aix-Marseille II University.

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Bruguerolle, B., Valli, M., Bouyard, L. et al. Circadian effect on carbamazepine kinetics in rat. European Journal of Drug Metabolism and Pharmacokinetics 6, 189–193 (1981). https://doi.org/10.1007/BF03189488

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  • DOI: https://doi.org/10.1007/BF03189488

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