Pharmacokinetics 2

Pharmacokinetics 2

1. drug distribution

   • plasma
   • interstitial fluid
   • transcellular fluid
   • intracellular fluid
   • VOLUME OF DISTRIBUTION
     • influenced by
       • size
       • protein plasma binding
       • endothelial cell barrier
       • ion trapping
       • lipid sol

2. Plasma protein binding

   • extent of drug binding to plasma proteins varies
   • species differences
   • displacement if 2 extensively plasma protein bound drugs given together
   • plasma protein bound and free drug in plasma = equilibrium
     • almost always free protein has the effect
   • consequences
     • pharmacodynamics
     • pharmacokinetics
     • toxicity
     • interactions

3. Drug metabolism

   • most drugs require metabolism prior to elimination
   • converts drugs into water sol compounds
   • some metabolites = metabolically active
   • some drugs administered as inactive form
   • sites of metabolism
     • LIVER = MAIN SITE
     • some may be metabolised in other tissues e.g. plasma
   • process
     • liver - must be lipophilic
     • hepatic - biphasic
       • PHASE 1
         • lipophilic --> polar molecules
         • PHASE 2
           • add conjugating group to molecule
             • increase polarity, decrease lipophilicity
     • P-450 or CYP enzymes involved
   • enterohepatic cycling
     • liver cells transfer drugs --> bile
       • delivered to intestines
         • conjugates = hydrolysed & reabsorption

4. excretion

   • occurs in urine and bile
   • water sol molecules eliminated
   • renal/hepatic
   • Renal
     • some filtered then actively secreted
       • secretion = active, energy dependent, use of transporter proteins
         • selective and saturable
     • some renally excreted by more than 1 mechanism
       • examples - penicillin