1. Pharmacokinetics: Drug Absorption
Course Coordinator
Jamaluddin Shaikh, Ph.D.
School of Pharmacy, University of Nizwa
Lecture-5
September 27, 2011

2. Pharmacokinetics

3. Mechanism of Drug Absorption
Except for IV route, all other routes require that the drug be transported from the site of administration into the systemic circulation. The transport of drugs across membrane involves one or more of the following:
Passive transport
Passive diffusion
Facilitated diffusion
Active transport
Filtration
Ion-pair transport
Endocytosis

4. Passive Diffusion
Separated by two compartments, the drug moves from a region of high concentration to a lower concentration
Does not involve a carrier
Lipid-soluble drugs readily move across biologic membranes due to solubility in the membrane bilayers
Water-soluble drugs penetrate the cell membrane through aqueous channels or pores

6. Facilitated Diffusion
Many of the characteristics associated with active transport, including being a protein carrier–mediated transport system
In contrast to active transport, facilitated diffusion dose not require energy to maintain normal cellular function
Concentration dependent, molecule transported from regions of higher to regions of lower concentrations
Initial rate of drug transfer will be proportional to the magnitude of the concentration gradient. Further increases in drug concentration no longer increase the transport rate, because binding sites on the carrier are now completely saturated 6

8. Active Transport
This mode of drug entry involves specific carrier proteins that span the membrane
Drugs that are actively transported across cell membranes using these specific carrier proteins
It is energy-dependent and is driven by the hydrolysis of ATP
Capable of moving drugs against a concentration gradient; that is, from a region of low drug concentration to one of higher drug concentration

9. Active Transport

10. Active Transport
Membrane

11. Passive Vs Active Transport

12. Filtration
Depends both on the existence of a pressure gradient as a driving force and on the size of the compound relative to the size of the pore through which it is to be filtered
In biological systems, the passage of many small water-soluble solutes through aqueous channels in the membrane is accomplished by filtration

13. Filtration
Membrane

14. Ion-pair Transport
Absorption of some highly ionized compounds e.g., sulfonic acids and quaternary ammonium compounds from the gastrointestinal tract follow this mechanism
These compounds are known to penetrate the lipid membrane despite their low lipid–water partition coefficients
It is postulated that these highly lipophobic drugs combine reversibly with such endogenous compounds as mucin in the gastrointestinal lumen, forming neutral ion pair complexes; it is this neutral complex that penetrates the lipid membrane by passive diffusion

15. Ion-pair Transport
Membrane

16. Endocytosis
This type of drug delivery transports drugs of exceptionally large size across the cell membrane
Involves engulfment of a drug molecule by the cell membrane and transport into the cell, e.g., vitamin B12 is transported across the gut wall by endocytosis
Exocytosis is the reverse of endocytosis and is used by cells to secrete many substances by a similar vesicle formation process, e.g., neurotransmitters are stored in membrane-bound vesicles in the nerve terminal and are released by exocytosis