Drug Absorption

Study Notes

Epithelial cell layer controls drug absorption; intestinal epithelium acts as a major barrier.
Transcellular pathway facilitates drug absorption by allowing drug molecules to partition into cell membranes.
Drug passage occurs at the apical side (mucosa) then through the basolateral side into systemic circulation, mostly via passive transport.
Passive transport is energy-independent, occurs through simple diffusion, and follows concentration gradients.
Predominantly applicable to small lipophilic compounds that can penetrate the phospholipid bilayer of cell membranes.

Lipophilic substances dissolve well in lipids and non-polar solvents.
Hydrophilic substances dissolve well in water and polar solvents.
Principle "like dissolves like"; lipophilic molecules tend to permeate cell membranes due to compatibility with lipid bilayer.

Simulated absorption using a mixture of lipophilic solvent (octanol) and hydrophilic solvent (water).
Distribution between the two phases indicates drug's lipophilicity; complete presence in octanol indicates high lipophilicity.

Higher Log P values indicate higher lipophilicity; lower Log P values indicate greater hydrophilicity.
Optimal Log P values determine gastrointestinal absorption efficiency for oral drugs.
Excessive Log P (e.g., > 5) can lead to bioaccumulation risks (e.g., polychlorinated biphenyls).

Ionization significantly impacts drug absorption; weak acids and bases can change lipophilicity based on medium pH (Log D).
Basic functional groups include amines; acidic functional groups include carboxylic acids and phenols.

Oral pharmaceuticals, like tablets, contain active pharmaceutical ingredients (API) and excipients which influence bioavailability.
API characteristics (physical state, particle size) affect absorption.
Excipients (fillers and lubricants) assist in drug manufacturing and release.

Bioequivalence studies evaluate the comparability of bioavailability between different formulations of the same drug.
Differences in absorption can arise from variations in drug release kinetics.
Pharmacokinetic parameters are assessed by comparing serum concentrations after administration.

Passive Targeting: Utilizes hypoxic conditions within tumors for localized drug activation.
Active Targeting: Involves drug conjugation to antibodies for specific tissue recognition.
Example: Ivacaftor for cystic fibrosis, altered by replacing hydrogen atoms with deuterium to enhance pharmacokinetics by reducing metabolic rates and improving efficacy and safety.

Drug Absorption - Oral Administration