Pharmokinetics

Pharmokinetics

1. Routes of drug administration

   • Enteral (Oral)
     • Advantages: easy to administer, limit the chances of infection in parental administration
     • Disadvantages: low bioavailability, absorption is affected by gastrointestinal (GI) environment, slow onset of action
   • Parental (eg. IV, IM, SC)
     • Advantages: avoids first-pass effect in liver, high bioavailability
     • Disadvantages: irreversible, contamination may lead to infections, rapid delivery causes adverse reactions
   • Others (eg. Inhalational, Topical

2. Drug dosage forms

   • Oral drugs
   • Sublingual drugs
   • Injectables
   • Others (eg. inhalational, topical)

3. Drug Absorption Process

   • Mechanisms of absorption
     • Endocytosis
     • Exocytosis
     • Active transport
     • Passive diffusion
   • Factors affecting absorption
     • Drug properties
     • Routes of administration
     • Blood flow to administration site
     • Surface area of absorption
     • Dosage forms of drugs
     • Drug-drug interaction
     • Disease status of the patient

4. Drug Distribution Process

   • Major compartments in the body
     • Plasma
       • Plasma drug concentration
         • Measure the total amount of drug in plasma (bound+unbound)
         • Plasma drug concentration under the curve
         • Factors affecting plasma drug concentrations
           • Route of drug administration
           • Mechanisms of ADME
           • Time of sampling
           • Solubility of the drug
     • Extracellular space
       • Drug crosses the capillary bed and into the interstitial fluide
     • Cells/tissues
       • Highly lipid soluble drugs are able to cross cell membranes

5. Drug BiotransformationProcess

   • Main purposes
     • Inactivate drug
     • Converting drugs to water-soluble form for elimination by the kidneys
   • Phase I
     • Convert parent drug to a more polar metabolite
       • Cytochrome P-450 used as a major enzyme
       • Phase II
         • Reaction of incorporated functional group in phase I with endogenous substrates to form highly polar conjugate that is eliminated by the kidney
   • Factors affecting biotransformation
     • Genetic differences
     • Liver diseases
     • Age
     • CYP enzyme induction/inhibition
   • First pass effect
   • Endotracheal Cycling

6. Drug Excretion Process

   • Routes of excretion
     • Renal
       • Filtration process
       • Secretion process
       • Reabsorption process
       • 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 tears

7. Various pharmacokinetic parameters

   • Bioavialability (F)
     • Fraction of chemically unchanged drug (%) that reaches the systemic circulation by any route
     • F= AUC (oral) / AUC (IV) X 100%
   • Volume of distribution (Vd)
     • Hypothetical volume of body fluid into which the absorbed drug is disseminated (if it were uniformly distributed)
     • Vd = total amount of drug in the body(mg) / drug blood plasma concentration[(mg/ml)
   • Clearance (Cl)
     • A measure of the capacity of the body to remove a drug
     • Cl = Rate of elimination(mg/ml) / C(mg/ml)
   • Half-life (t1/2)
     • Time required for concentration of drug to be reduced by half
   • Loading dose (DL)
     • A single dose required to achieve desired plasma drug concentration (Cp, desired)
     • F x DL = Vd x Cp, desired
   • Steady-state plasma concentration (CSS)
     • Repeated dosing of a drug at regular intervals, the plasma concentration increases until a steady state is reached

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