At which site of absorption will a weakly basic drug with a pKa of 7.8 pass through the membrane most readily when administered orally?

The most favorable site of absorption for a weakly basic drug, such as the one described with a pKa of 7.8, is the jejunum, where the pH is approximately 8.0. Weakly basic drugs tend to be more readily absorbed in environments that are more alkaline than their pKa.

In this case, when the pH exceeds the pKa of the drug, the drug exists predominantly in its non-ionized form. This non-ionized state is more lipid-soluble, allowing it to pass through biological membranes more easily. At a pH of 8.0, the drug is mostly non-ionized, which significantly enhances its ability to be absorbed into the bloodstream.

In contrast, at a lower pH, such as the stomach with a pH of 2.5, the weakly basic drug would predominantly be protonated and exist in an ionized form, which diminishes its lipid solubility and reduces absorption. The mouth and duodenum, while having pH levels closer to the pKa, do not provide the optimal alkaline environment needed for maximum absorption of the weakly basic drug when compared to the jejunum. Thus, the jejunum represents the most favorable site for