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Saturable rate of cefatrizine absorption after oral administration to humans

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Abstract

This study examined the absorption kinetics of cefatrizine, an amino-β-lactam antibiotic, after oral administration of a single 500-mg dose to 12 healthy volunteers. Plasma concentrations were determined by high performance liquid chromatography. The plots of the percentage of drug unabsorbed and the apparent rate of cefatrizine absorption as a function of time showed, first, a delay and, then, an almost constant rate of absorption with a tendency to move toward first-order kinetics at the end of the process. Three compartmental models incorporating a lag time and first-order elimination kinetics, but differing in their input rate, were used for analysis of the time course of cefatrizine plasma concentrations. The model with first-order absorption kinetics was clearly inadequate. The results were improved with the model for which the rate of absorption is constant, but a model incorporating saturable absorption kinetics of the Michaelis-Menten type improved the fit further. This last model was statistically superior to the constant-rate input model in 6 out of 12 subjects, according to the likelihood-ratio method. Because of the innovative feature of the model incorporating the Michaelis-Menten equation, simulations of the effect of altering the model parameters and the dose administered on the concentration-time profile, were performed. Different hypotheses which might explain why cefatrizine absorption kinetics fits the Michaelis-Menten equation were examined. The observation of saturable absorption kinetics is consistent with a carrier-mediated transport previously reported to occur in the gastrointestinal tract of rats.

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Authors and Affiliations

  1. Department of Pharmacy, School of Pharmacy, University of California, 94143, San Francisco, California, USA

    Bruno G. Reigner & Thomas N. Tozer

  2. CEMAF, 144 rue de la Gibauderie, 86000, Poitiers, France

    William Couet & Jean-Bernard Fourtillan

  3. Lycée Descartes, 37000, Tours, France

    Jean-Paul Guedes

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  1. Bruno G. Reigner
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  4. Jean-Bernard Fourtillan
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  5. Thomas N. Tozer
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Reigner, B.G., Couet, W., Guedes, JP. et al. Saturable rate of cefatrizine absorption after oral administration to humans. Journal of Pharmacokinetics and Biopharmaceutics 18, 17–34 (1990). https://doi.org/10.1007/BF01063620

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  • DOI: https://doi.org/10.1007/BF01063620

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