Chemistry Reference
In-Depth Information
(plasma decomposition) for those molecules that survive in the liver. First-pass
effect or presystemic metabolism represents the presystemic drug elimination
which occurs during the first-pass through the liver where the concentration of a
drug is highly reduced. Drugs such as imipramine, morphine, propranolol,
diazepam, cimetidine and lidocaine have a reduced bioavailability due to the
presystemic metabolism [10, 14].
Hence, it is important to distinguish between oral bioavailability and absorption,
whereas the oral bioavailability is the ratio of both the absorption and the hepatic
first-pass metabolism. Therefore, the main difference between absorption and
bioavailability is the amount of drug eliminated by secretion or first-pass
metabolism through the liver [9].
The GIT absorption process can be altered by several factors, classified into three
main classes:
physicochemical (pKa, solubility, chemical stability, diffusivity,
lipophilicity and salt form);
physiological (gastrointestinal pH, gastric passage, small and large
intestine transit time, active transport and efflux, and gut wall
metabolism);
formulation factors (drug particle size and crystal form, and dosage
form such as a solution, tablet, capsule, suspension, emulsion, gel, and
modified release).
Regarding absorption studies the major efforts are focused on the
physicochemical properties of compounds, because the physiological
factors cannot be controlled and the formulation specificities are usually
experimentally optimized. The main mechanism for drug absorption
through intestinal epithelium is passive diffusion driven by a
concentration gradient. Depending on the molecule's hydrophobicity,
passive diffusion can occur through the lipid/aqueous environment of the
cell membrane (trans-cellular transport) or the passage through the water-
filled tight junctions formed by the fusion of the lipid membranes of
