Pharmacokinetics

Pharmacokinetics

1. Actions of the Body on Drugs

   • Involves 4 processes
     • Absorption
     • Distribution
     • Metabolism
     • Elimination

2. Routes of Drug Administration

   • Enteral
     • Oral
       • Solid dosage
         • Capsules Tablets Granules Powders
       • Liquid dosage
         • Emulsions Solutions Suspensions Syrups
     • Sublingual
       • Chewing gum Lozenges Sprays Tablets
   • Parenteral
     • Intravenous
     • Intramuscular
     • Intradermal
     • Subcutaneous
     • Intraperitoneal
     • Epidural
     • Intrathecal
     • Intracerebroventricular
     • Solution Oil Powder
   • Others
     • Inhalation
       • Aerosols Gases
     • Intranasal
       • Sprays Drops OIntments
     • Topical
       • Creams Gels Ointments Sprays
     • Transdermal
       • Patches Plasters
     • Rectal
       • Suppositories Enemas

3. Drug Absorption Process

   • Site of absorption of oral drugs
     • Stomach
     • Small intestines
   • Mechanisms of drug absorption
     • Passive diffusion
     • Active tranport
     • Endocytosis
     • Exocytosis
   • Factors affecting absorption
     • Drug properties
       • Size
       • Hydrophilicity and hydrophobicity
       • pKa of drug
       • Chemical stability of drug
     • Routes of administration
     • Blood flow to site of administration
     • Surface area for absorption
     • Dosage form
     • Drug-drug interaction
     • Disease status

4. Drug Distribution Process

   • To major compartments in body
     • Plasma
       • Free drug = active
       • Bound drug = inactive
       • Factors affecting plasma drug concentration
         • Route of administration
         • Mechanism of ADME
         • pH and ionization status
         • Absorptive surface area
         • Blood supply to area
         • Solubility of drug
         • Dosage form
         • Time of sampling
         • Drug-drug interaction
       • Movement from plasma to interstitium depends on
         • Drug properties
         • Blood flow
         • Capillary permeability
         • Binding of drugs to proteins
     • Extracellular space (interstitium)
     • Cells/tissues

5. Drug Biotransformation Process

   • Phase I
     • Convert parent drug to more polar metabolite
       • Major enzyme: Cytochrome P-450
         • Reactions: Oxidation Reduction Hydrolysis
   • Phase II
     • Drug not eliminated in phase I
       • Make drug water-soluble for elimination
         • Enzyme: glucuronyl transferase
           • Reaction: Glucuronidation
   • Factors affecting biotransformation
     • Genetic differences
     • Liver diseases
     • Age
     • CYP enzyme induction/inhibition
   • First pass effect
     • Oral and intra-peritoneal drugs
       • Pass through liver first
         • Liver metabolizes the drug
           • Drug level reaching circulation less than actual dose
   • Enterohepatic cycling
     • Drug excreted through bile
       • Reabsorbed in small intestine
         • Recycled back to the liver through hepatic portal vein
           • Returned to systemic circulation
             • Prolonging the drug effect

6. Drug Excretion

   • Renal
     • Filtration
       • Through glomerulus
         • Glomerular Filtration Rate (GFR)
     • Secretion
       • In proximal convoluted tubule
     • Reabsorption
       • In distal convoluted tubule
     • Factors affecting renal excretion
       • Urine pH
       • Urine flow rate
       • Plasma protein binding
       • Competition for active tubular secretion
       • State of renal function
   • Fecal
   • Lung
   • Milk
   • Sweat, saliva and tears

7. Parameters

   • Bioavailability (F)
   • Volume of distribution (Vd)
   • Clearance (Cl)
   • Half-life (t1/2)
   • Loading dose (DL)
   • Steady-state plasma concentration (Css)

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