1. Pharmacokinetics: Drug Absorption
Course Coordinator
Jamaluddin Shaikh, Ph.D.
School of Pharmacy, University of Nizwa
Lecture-6
October 01, 2011

2. 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

3. 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

4. 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

5. 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
Pulmonary absorption of volatile anesthetics across the alveolar–capillary barrier is very rapid

6. 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

7. 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

8. 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 pH

9. Factors Influencing Absorption, continued…..
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

10. Factors Influencing Absorption, continued…..
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

11. What is the Role of pH on Absorption?
Most drugs are either weak acids or weak bases.
Acidic drugs (HA) release an H+ causing a charged anion (A-) to form:
HA H+ + A-
Weak bases (BH+) can also release an H+. However, the protonated form of basic drugs is usually charged, and loss of a proton produces the uncharged base (B):
B H B + H+

12. 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

13. To systemic circulation
Bioavailability
Destroyed in gut
Not absorbed
Destroyed by gut wall
Destroyed by liver
Dose
To systemic circulation

14. 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

15. Bioequivalence
When the bioavailability of two drugs given orally is similar, these drugs are known as bioequivalent

16. Therapeutic Equivalence
When the efficacy and safety of two drugs is similar, these drugs are known as therapeutic equivalent

17. 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