Effects of diffusional barriers on the extent of presystemic and systemic intestinal elimination of drugs
1997
Kwon, Younggil
In the present study, a pharmacokinetic model to address the effects of the diffusional barrier between splanchnic bed and enterocytes on the extent of presystemic and systemic intestinal elimination of drugs was developed. The model is composed of five compartmentsi.e., gut lumen, enterocyte, splanchnic bed, liver and central compartments. The equations for various pharmacokinetic parameters important for estimating the quantitative differences between prresystemic and systemic intestinal and hepatic elimination of drugs were derived. A simulation study demonstrated that the diffusional barrier present between splanchnic blood and enterocytes can have significant effects on oral bioavailability and systemic clearance of drugs. In conclusion, the model can be useful for a better understanding of the effects of diffusional barrier on the extent of administration-route dependent intestinal and hepatic elimination of drugs, especially those with high hydrophilicity and/or charge(s) under physiological conditions.
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