Mechanisms of transport across the gastrointestinal membrane There are two main mechanisms of drug transport across the gastrointestinal epithelium: transcellular (i.e. Therefore the rate of appearance of drug in the blood at the absorption site is given by d d C t = - k   where dC/dt is the rate of appearance of drug in the blood at the site of absorption, k is the proportionality constant, Cg is the concentration of drug in solution in the gastrointestinal fluid at the absorption site and Cb is the concentration of drug in the blood at the site of absorption.Hepatic metabolism
The liver is the primary site of drug metabolism and
thus acts as a final barrier for oral absorption.The bioavailability of
sustained-release propranolol is even less as the drug
is presented via the hepatic portal vein more slowly
than from an immediate-release dosage form, and
the liver is therefore capable of extracting and
metabolizing a larger portion.The bioavailability of a susceptible drug may be
reduced to such an extent as to render the gastro-
intestinal route of administration ineffective, or to necessitate an oral dose which is many times larger
than the intravenous dose (e.g. propranolol).The proportionality constant k incorporates the diffusion coefficient of the drug in the gastrointestinal membrane (D), and the thickness (h) and surface area of the membrane (A): k A h = D

Thus the small 
intestine, primarily the duodenum, is the major site 
of drug absorption, owing principally to the presence 
of villi and microvilli, which provide such a large 
surface area for absorption (discussed earlier in this 
chapter).Specific membrane transport-
ers are expressed in the luminal and/or basolateral 
membranes of enterocytes, hepatocytes, renal tubular epithelial cells and other important barrier tissues, 
including the blood-brain barrier, blood-testis barrier 
and the placental barrier.Transcytosis is also a means by which some viruses, 
bacteria and prion proteins can gain entry to the 
lymphatic system through absorption by enterocytes 
and specialized cells (M cells) in the gut-associated 
lymphoid tissue (GALT).In summary, drugs can be absorbed via passive 
diffusion, via membrane transporters or carrier-
mediated pathways, paracellular transport or trans-
cytosis.Noncompetitive inhibition occurs when the inhibitor 
binds not to the transporter active site but to an 
allosteric site, which lowers the affinity of the 
transporter for the substrate due to changing the 
conformation of the transporter.Many peptide-like drugs, such as the penicillins, 
cephalosporins, angiotensin-converting enzyme (ACE) 
inhibitors and renin inhibitors, rely on the peptide 
transporters for their efficient absorption.