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Abstract
This report describes an extended compartmental absorption and transit (CAT) model to estimate saturable small intestinal absorption. This model simultaneously considers passive absorption, saturable absorption, degradation, and transit kinetics in the human small intestine. Using cefatrizine as a model drug, we demonstrated that the extended CAT model, along with intravenous pharmacokinetic parameters, was able to explain the observed oral plasma concentration-time profiles. The model predicted comparable passive and saturable absorption characteristics for cefatrizine, particularly at high dose. The predicted fraction of dose absorbed was 74% at 250 mg, 61% at 500 mg, and 48% at 1000 mg, in agreement with the reported experimental data. The simulation study showed that no single physiological factor (gastric emptying, small intestinal transit, and absorption mechanism) could account for the large variability of cefatrizine absorption observed in the literature.
Published Version
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