The gastric secretion of drugs: a pH partition hypothesis.

Parenterally administered drugs are secreted directly into the gastric juice. The concentration ratio (concentration of drug in gastric juice divided by concentration in plasma) depends on the dissociation constant of the drug. Thus strong acids appear in gastric juice in negligible concentration, weak acids and weak bases in measurable amount and stronger bases in highest concentration. The stronger bases appear in a limiting concentration ratio of about 40 to 1 when gastric juice flow is maximal, the limitation apparently being due to complete clearance by the gastric mucosa. The pattern of drug secretion can be explained by the concept that the membrane separating plasma from gastric juice has the characteristics of a lipoid membrane that allows the passage of drugs in their undissociated form while restricting passage of dissociated form.