Transport of model compounds across the peritoneal membrane in the rat

The absorption into the systemic circulation of compounds administered intraperitoneally in large volumes was investigated in the rat. The influence on absorption of molecular weight, lipid-water partition coefficient (K), and dissociation constant (pKa) was studied. Nine neutral compounds ranging in molecular weight from 18 to 2 million demonstrated absorptions that decreased with increasing molecular weight. Five compounds were tested with variable lipid partition (K) values (0.001--3.3) and the absorptions increased from 57 to 96% as the K values increased. A series of nine acids and bases covering a wide range of pKa values )0.9--9.9) were investigated. For the acids, absorption increased with increasing pKa value, while for the bases absorption decreased with increasing pKa. For both groups of compounds absorption was directly related to the extent of ionization at physiologic pH. As has been documented for other biological membranes, the peritoneal membrane in the rat was found to behave in a lipoid manner. Unionized or lipid-soluble compounds are absorbed to a greater extent than ionized or lipid-insoluble compounds, and neutral compounds are absorbed in relation to their molecular weights.