In vitro studies of poorly absorbed drugs using porcine intestine in the ring model RIMO.
Two compounds, an aminobisphosphonate (A) and a steroid (B), showing a very large difference in lipophilicity (log PC (A) = O, log PC (B) > 8) but both revealing very poorly absorption in vivo of less than 1% were tested in respect of in vitro absorption and mucoadhesion using a model with porcine intestine named RIMO (ring model). Explanations for the poor absorption of the two compounds were investigated in order to propose methods for absorption enhancement. Moreover, absorption and mucoadhesion were measured for different parts of intestine with radiolabelled substances. Last but not least the inhibiting effect of calcium ions was investigated as well as enhancement by DTT (dithiothreitol), EDTA and bile. Results showed that mucus plays an important role in oral bioavailability. The aminobisphosphonate formed a complex with calcium ions which was insoluble in the mucus and resulted in a smaller amount of substance being absorbed. The very lipophilic steroid was kept back from the mucosa by the hydrophilic mucus, but addition of the solubilizer bile increased the absorption. The results were in good agreement with in vivo bioavailability data. Therefore, simplicity of the model and easy access of porcine intestine by slaughter houses make RIMO a valuable tool for investigations concerning the role of mucus and influences of diverse additives on absorption.
Nolte
K
K
Bayer AG, Pharma, Quality Assurance, Leverkusen, Germany.
Backfisch
G
G
Neidlein
R
R
D000268:Adhesiveness; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D013552:Swine
D002118:Calcium