Prediction of human intestinal permeability using artificial membrane permeability.
The purpose of the present study was to examine a correlation between the human intestinal permeability (P(eff)) and the bio-mimetic artificial membrane permeability corrected by the paracellular pathway model based on the Renkin function (P(PAMPA-PP-RF)) and to construct a prediction scheme. The effect of the unstirred water layer was incorporated to the prediction scheme. Eighteen P(eff) values of passively absorbed drugs were employed for the analysis. The correlation coefficient (CC) between the predicted and observed logP(eff) was 0.91. P(eff) of furosemide, hydrochlorothiazide and creatinine were underestimated by P(PAMPA-PP-RF). When these compounds were excluded, CC was 0.97. Without the correction for the paracellular pathway, P(eff) of small, cationic and hydrophilic compounds were underestimated. Therefore, P(PAMPA-PP-RF) was found to be an adequate in vitro surrogate for P(eff).
Sugano
Kiyohiko
K
Pre-clinical Research Department I, Chugai Pharmaceutical Co. Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan. suganokyh@chugai-pharm.co.jp
Nabuchi
Yoshiaki
Y
Machida
Minoru
M
Aso
Yoshinori
Y
D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008567:Membranes, Artificial; D010539:Permeability
D008567:Membranes, Artificial