Pharmacokinetics: Drug Absorption Course Coordinator Jamaluddin Shaikh, Ph.D. School of Pharmacy, University of Nizwa Lecture-5 February 19, 2012

Pharmacokinetics

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

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

Facilitated Diffusion A protein carrier–mediated transport system Dose not require energy Concentration dependent, molecule transported from regions of higher to regions of lower concentrations 5

Active Transport Specific carrier proteins needed that span the membrane 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

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 Membrane

Ion-pair Transport Absorption of some highly ionized compounds e.g., sulfonic acids and quaternary ammonium compounds from the gastrointestinal tract follow this mechanism 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 Membrane

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 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 released by exocytosis

Passive Vs Active Transport