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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.

Food ingestion can influence the absorption of levodopa in the intestine and thereby contribute to fluctuations of motor functions in Parkinson patients. Obstruction of the active transport of levodopa by amino acids can be one factor. Paracellular drug absorption, a route proposed to be influenced by net transport of water across the intestinal epithelium, might occur for a small and hydrophilic drug such as levodopa. In the present study we studied how luminal L-leucine (60 mmol/L), alone or combined with hypotonicity, might stimulate net water absorption, and levodopa uptake in the human small intestine, since this possibly can contribute to the variable intestinal absorption of levodopa. The Loc-I-Gut perfusion technique was used in 10 healthy volunteers to study the effects of induced net fluid absorption on the small intestinal absorption of levodopa (2.5 mmol/L). An induced net fluid absorption was observed only when L-leucine was combined with a hypoosmolar perfusion solution. However, this did not enhance the intestinal permeability of levodopa. In conclusion, we suggest that the variability in the absorption of levodopa in Parkinson’s disease cannot be explained by differences in transmucosal water flux in the human small intestine.