Pharmacokinetics: ABSORPTION

Absorption is the transfer of a substance from the site of application to the blood stream (usually the systemic circulation).

"Bioavailability" is defined as the fraction of unchanged drug reaching the systemic circulation following administration by any route.

Absorption of Drugs from the GI Tract

• For drugs administered orally, bioavailability may be less than 100% because of either incomplete extent of absorption or first-pass elimination (in both the gut and the liver). First pass effect refers to hepatic inactivation of certain orally administered drugs. Drugs administered via the GI tract are termed enteral. All other forms of administration are parenteral, however this term is often reserved for injected drugs.

• Drugs given with fluid on an empty stomach will quickly pass from the stomach into the intestine. Most drugs given with food will have delayed absorption because of delayed stomach emptying.

• Solid oral dosage forms (e.g., tablets, capsules) must first disintegrate, then must dissolve in the intestinal fluids. Drugs, to be absorbed, must be a mix of water solubility (to dissolve in the GI fluids; drugs must be solubilized to be absorbed) and lipid soluble (to cross the lipid plasma membrane). Drugs may be too hydrophilic (e.g., nadolol) or lipophilic (e.g., acyclovir) to be absorbed easily. Some drugs, particularly water-soluble compounds (e.g., amino acids) are absorbed by an active transport mechanism.

• When absorbed from the intestine, drugs travel via the portal vein to the liver where some drugs are extensively metabolized before reaching the systemic circulation (e.g., nitroglycerin; propranolol). This effect is termedfirst pass effect . Sublingual & transdermal administration avoids hepatic first pass effect. Drugs with a large first pass effect have a low bioavailability.

Drugs may be nebulized & inhaled, some with rapid absorption of drug with avoidance of first pass effect and, in the case of pulmonary disease, local application of the drug at the desired site of action. Disadvantages: With inhalation administration, it may be difficult to regulate the dose and inhalation is a cumbersome method of administration. Some drugs irritate the pulmonary epithelium and aerosol particles larger than 1 micrometer fail to reach alveoli.

Category: Pharmacology Notes