Prediction of passive intestinal absorption using bio-mimetic artificial membrane permeation assay and the paracellular pathway model.
The purpose of this study was to construct and examine the prediction model for total passive permeation through the intestinal membrane. The paracellular pathway prediction model based on Renkin function (PP-RF) was combined with a bio-mimetic artificial membrane permeation assay (BAMPA), which is an in vitro method to predict transcellular pathway permeation, to construct the prediction model (BAMPA-PP-RF model). The parameters of the BAMPA-PP-RF model, e.g. apparent pore radius and potential drop of the paracellular pathway, were calculated from BAMPA permeability, the dissociation constant, the molecular radius and the fraction of a dose absorbed in humans consisting of 80 structurally diverse compounds. The apparent pore radius and the apparent potential drop obtained in this study were 5.61-5.65 A and 75-86 mV, respectively, and these were in accordance with the previously reported values. The mean square root error of the BAMPA-PP-RF model was 13-14%. The BAMPA-PP-RF model was shown to be able to predict the total passive permeability more adequately than BAMPA alone.
Sugano
Kiyohiko
K
Drug Metabolism and Pharmacokinetics Laboratory, Fuji Gotemba Research Labs, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan. suganokyh@chugai-pharm.co.jp
Takata
Noriyuki
N
Machida
Minoru
M
Saitoh
Kimitoshi
K
Terada
Katsuhide
K
D006801:Humans; D007408:Intestinal Absorption; D008567:Membranes, Artificial; D008954:Models, Biological; D010539:Permeability; D010599:Pharmacokinetics; D011237:Predictive Value of Tests
D008567:Membranes, Artificial