The greater proportion of the dose of a drug administered orally will be absorbed in the small intestine. However, on the assumption that passive transport of the nonionized form of a drug determines its rate of absorption, which of the following compounds will be absorbed to the least extent in the stomach?
1.Ampicillin()pKa=2.5
2.Aspirin Pka 3.0
4.Phenobarbital PK
5.Propharnolol
View explanation
Weak acids and weak bases are dissociated into nonionized and ionized forms, depending upon the pKa of the molecule and the pH of the environment. The nonionized form of a drug passes through cellular membranes more easily than the ionized form because it is more lipid soluble. Thus, the rate of passive transport varies with the proportion of the drug that is nonionized. When the pH of the environment in which a weak acid or weak base drug is contained is equal to the pKa, the drug is 50% dissociated. Weak acids (e.g., salicylates, barbiturates) are more readily absorbed from the stomach than from other regions of the alimentary canal because a large percentage of these weak acids are in the nonionized state. The magnitude of this effect can be estimated by applying the Henderson-Hasselbalch equation:
At an acidic pH of about 3, of the drugs in question, all are weak acids except propranolol; therefore, propranolol has the greatest percentage of its molecules in the ionized form in the stomach. The higher the value of the pKa, the less ionized these substances are in the stomach.