ADVERTISEMENTS:
ADVERTISEMENTS:
This article throws light upon the three main factors decreasing the bioavailability of drugs. The factors are: 1. Inactivation 2. First Pass Effect 3. Enterohepatic Recycling.
Factor # 1. Inactivation:
Inactivation by gastric acid enzymes, bacterial flora.
Factor # 2. First Pass Effect:
Drug absorbed distal to the oral cavity and proximal to the rectum enters the portal circulation and is transported directly to the liver, where biotransformation may occur, which results in a significant “first pass” biotransformation of the absorbed compound.
ADVERTISEMENTS:
Drugs that are too polar to be absorbed across the gastrointestinal wall are formulated as ester conjugates to increase the lipid solubility enhance absorption once the drug crosses the GI epithelium in this form, subsequent first pass hepatic biotransformation enzymes and circulating blood and mucosal esterases cleave off the ester moiety, releasing free drug into the systemic circulation.
Sub lingual absorption provides direct access to systemic not portal veins. The transdermal route offers the same advantage. 50% of a rectal does can be assume to bypass the liver.
Factor # 3. Enterohepatic Recycling:
GI tract eliminates non absorbed solid wastes and other metabolite by-products excreted in the bile. The bile duct drains into upper small intestine. This results in enterohepatic recycling, whereby drug excreted into the bile from systemic circulation and is reabsorbed from the small intestine back into the blood stream.
Some drugs metabolised by Phase -II conjugation reactions are “unconjugated” by resident bacterial flora, which generates free drug for reabsorption. These compounds have a prolonged efficacy in the body because of continuous intestinal reabsorption.
ADVERTISEMENTS:
Oral preparations have lower bioavailability because of incomplete absorption and metabolism. However, certain preparations are made not to be absorbed e.g., gut acting sulfonamides meant to act in GI tract anthelmintics, certain antibiotics (neomycin).
Bioavailability of active drug in solid dosage form is dependent on:
(i) Disintegration of the drug product and release of the active drug particles.
(ii) Dissolution of the drug
(iii) Absorption and permeation of the drug across cell membrane.
Any factor that affects any of these three steps can alter bioavailability and hence its therapeutic effects.
