Page 159 - Interactive Theoritical Notes of Bioharmaceutics and pharamcokinetics.docx compressed

PharmD clinical pharmacy program Level 3, Semester 2 Biopharmaceutics & Pharmacokinetics (PT608(

Gut wall metabolism

 The gut walls contain a number of metabolizing enzymes that can degrade drugs
before they reach the systemic circulation.

 For example, the major cytochrome P450 enzyme CYP3A, present in the liver
and responsible for the hepatic metabolism of many drugs, is present in the

intestinal mucosa and intestinal metabolism may be important for substrates of this
enzyme.

 This effect can also be known as first-pass metabolism by the intestine.

 CYP level tends to be higher in the intestine than in the colon.

Hepatic metabolism

The liver is the primary site of drug metabolism and thus acts as a final barrier for oral

absorptionExamples for drugs susceptible to the first-pass effect:

Propranolol, atorvastatin, Lidocaine

 To overcome hepatic first pass metabolism:

1. Increase the oral dose or

2. Use other routes e.g. sublingual nitroglycerin and i.v. lidocaine.

Enterohepatic cycling

 The liver may secrete drugs or their metabolites into bile that is stored in the

gallbladder.

 The gallbladder empties the bile (and any drugs or metabolites in it) into the

intestine in response to food entering the intestinal tract.

 Any drugs or metabolites contained in the bile may be reabsorbed or simply

eliminated within the feces.
 If the drugs or metabolites are reabsorbed back in the small intestine into the blood

circulation, this is called enterohepatic cycling; where the drugs or metabolites are
then returned to the liver to be recycled.

158