Pharmacokinetics: Drug Absorption Course Coordinator Jamaluddin Shaikh, Ph.D. School of Pharmacy, University of Nizwa Lecture-6 February 20, 2012

Absorption from Oral Cavity Drugs absorbed from the oral cavity enter the general circulation directly Although the surface area of the oral cavity is small, absorption can be rapid if the drug has a high lipid–water partition coefficient and can readily diffuse through lipid membranes The extensive network of blood vessels facilitates rapid drug absorption

Absorption from GI Tract Small Intestine: With large surface area, a greater capacity for absorption Diffusion is the main process of absorption Facilitated transport, active transport, endocytosis, and filtration are also possible Conditions that shorten intestinal transit time (e.g., diarrhea) decrease intestinal drug absorption, while increases in transit time will enhance intestinal absorption Large Intestine Small Intestine

Absorption from GI Tract Large Intestine: Smaller absorptive surface area than the small intestine, but it may still serve as a site of drug absorption, especially for compounds that have not been completely absorbed from the small intestine The most distal portion of the large intestine, the rectum, can be used directly as a site of drug administration Large Intestine

Absorption from Lung The lungs serve as a major site of administration for a number of agents Absorption is facilitated by the large surface area and limited thickness of the pulmonary alveolar membranes, and the high blood flow to the alveolar region

Absorption from Skin Outer layer of the epidermis, forms a barrier against the rapid penetration of most drugs The dermis, on the other hand, is well supplied with blood and capillaries and therefore is permeable to both lipid-soluble and water-soluble compounds Lipid-insoluble compounds may absorbed by diffusion through the hair follicles, or sweat glands

Absorption After Parenteral Administration Absorption from IM and SC sites depends on the quantity and composition of connective tissue, and capillary density Advantages of IM and SC routes include a rapid absorption and onset of drug action

Factors Influencing Absorption Molecular Size Solubility of drugs at the site of administration Concentration of drugs Route of administration Blood flow to the site of administration Total surface area available for absorption Contact time at the site of administration

Factors Influencing Absorption, cont… Molecular size: Absorption is inversely proportional to the molecular size of the drug Solubility of drugs at the site of administration: Drugs given in aqueous solution are more rapidly absorbed than those given in suspension or solid form Concentration of drugs: Absorption, in general, is proportional to the concentration of the drug at the site of action Route of administration: Except IV, all other routes affects on absorption differently

Factors Influencing Absorption, cont.. Blood flow to the site of administration: Greater the blood flow at the site of absorption, higher will be the absorption Total surface area available for absorption: More the surface area, more the rate of absorption Contact time at the absorptive surface: If a drug moves through the GI tract very quickly, as in severe diarrhea, it is not well absorbed. Conversely, absorption is increased in constipation

To systemic circulation Bioavailability Bioavailability is the fraction of administered drug that reaches the systemic circulation Bioavailability is expressed as the fraction of administered drug that gains access to the systemic circulation in a chemically unchanged form For example, if 100 mg of a drug are administered orally and 70 mg of this drug are absorbed unchanged, the bioavailability is 0.7 or seventy percent Destroyed in gut Not absorbed Destroyed by gut wall Destroyed by liver Dose To systemic circulation

Factors that influence bioavailability First-pass hepatic metabolism: When a drug is absorbed across the GI tract, it enters the portal circulation before entering the systemic circulation. If it is rapidly metabolized by the liver, the amount of unchanged drug that gains access to the systemic circulation is decreased. Solubility of the drug: Hydrophilic drugs are poorly absorbed because of their inability to cross the lipid-rich cell membranes Chemical instability: Some drugs are unstable in the pH of the gastric contents Nature of the drug formulation: Drug absorption may be altered by particle size, salt form, and enteric coatings

Therapeutic Equivalence Bioequivalence When the bioavailability of two drugs given orally is similar, these drugs are known as bioequivalent Therapeutic Equivalence When the efficacy and safety of two drugs is similar, these drugs are known as therapeutic equivalent

To systemic circulation Study Question Suppose, 100 mg of drug A are administered orally and 60 mg of this drug are available unchanged in the systemic circulation; whereas, 80 mg of a drug B are administered orally and 48 mg of this drug are available unchanged in the systemic circulation. What are the bioavailability of drugs A and B? Answer Destroyed in gut Not absorbed Destroyed by gut wall Destroyed by liver Dose To systemic circulation A= 100 mg B = 80 mg A= 60 mg B = 48 mg Calculation A: 60/100= 0.6 or 60% B: 48/80 = 0.6 or 60% Conclusion: A and B are Bioequivalence