ABSTRACT
The rate and extent of intestinal drug absorption (mass/time and mass/dose, respectively) in vivo are affected by several factors, such as dose/dissolution ratio, chemical instability, luminal localized metabolism, complex binding, intestinal transit, and effective permeability (P,11 ) across the intestinal mucosa. The extent of drug absorption (M(t)/dose) (i.e., the fraction of drug disappearing from the intestinal lumen during a certain residence time, assuming no luminal reactions), at any time tis (1,2):
M(t) f' -- = APerrClumen · dAdt dose o
where A is the available intestinal surface area, P,11 is the average value of the effective intestinal permeability in the gut region at which drug absorption occurs, and C1umen is the drug concentration in the intestinal lumen
available for absorption (1 - 5). Intestinal P,rr is one of the key variables controlling the overall intestinal absorption rate and extent, and may be used regard less of the transport mechanism(s) across the intestinal mucosa (1,2). Consequently, there are several reasons why this biopharmaceutical-pharmacokinetic variable should be investigated in both drug discovery and development.
