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- Source :
- Pharmaceutical Research. 13:1336-1342
- Publication Year :
- 1996
- Publisher :
- Springer Science and Business Media LLC, 1996.
-
Abstract
- Purpose. Our main aim is to determine the effective intestinal permeability (Peff) in the rat jejunum in situ for 10 compounds with different absorption mechanisms and a broad range of physico chemical properties, and then compare them with corresponding historical human in vivo Peff values. Methods. The rat Peff coefficients are determined using an in situ perfusion model in anaesthetized animals. The perfusion flow rate used is 0.2 ml/min, which is 10 times lower than that used in humans. The viability of the method is assessed by testing the physiological function of the rat intestine during perfusions. Results. The Peff for passively absorbed compounds is on average 3.6 times higher in humans compared to rats (Peff,man = 3.6 · Peff,rat + 0.03·10−4; R^2 = 1.00). Solutes with carrier-mediated absorption deviate from this relationship, which indicates that an absolute scaling of active processes from animal to man is difficult, and therefore needs further investigation. The fraction absorbed of drugs after oral administration in humans (fa) can be estimated from 1 − e−(2·P eff,man ·t res /r·2.8). Conclusions. Rat and human jejunum Peff estimates of passively absorbed solutes correlate highly, and both can be used with precision to predict in vivo oral absorption in man. The carrier-mediated transport requires scaling between the models, since the transport maximum and/or substrate specificity might differ. Finally, we emphasize the absolute necessity of including marker compounds for continuous monitoring of intestinal viability.
- Subjects :
- Pharmacology
Pathology
medicine.medical_specialty
Chromatography
Intestinal permeability
Organic Chemistry
Pharmaceutical Science
Biology
medicine.disease
Transport maximum
Intestinal absorption
Bioavailability
Jejunum
medicine.anatomical_structure
Pharmacokinetics
In vivo
medicine
Molecular Medicine
Pharmacology (medical)
Perfusion
Biotechnology
Subjects
Details
- ISSN :
- 07248741
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Pharmaceutical Research
- Accession number :
- edsair.doi...........2e489156efa546f446e6c5554f9de6be
- Full Text :
- https://doi.org/10.1023/a:1016065715308