Introduction to Veterinary Pharmacokinetics:

Drug Elimination

Elimination by the liver

Biotransformation - conversion of a drug entity to a metabolite

Chemical mechanisms

  • Oxidation, hydroxylation, hydrolysis, reduction, conjugation (acetylation, glucuronidation, sulfation, etc.)

Rates, clearance controlled by...

  • Metabolic activity for a specific drug
  • Blood flow to the organ
  • Health of the organ and health of the circulatory system

Organs involved

  • Liver (most important for most drugs)
  • Lungs (especially for autocoids)
  • Kidneys

Stylized representation of hepatic metablism, note that the ratio of drug entering the liver to that leaving the liver remains constant, despite the change in concentration. NOTE: This principle applies to all routes of elimination.

Biliary excretion

Active secretion
Passive secretion

Elimination by the kidneys

Overall renal elimination can be a combination of three processes:

(Glomerular filtration + tubular secretion) - passive reabsorption = renal elimination

Glomerular filtration (all unbound drug - in plasma water - ends up in in GF)

  • passive elimination of drug dissolved in plasma water
  • ionized and unionized
  • NOT protein bound drug

Tubular secretion (only a few drugs, even protein bound)

  • energy dependent excretion by proximal kidney tubule
  • organic acid and organic base pumps
  • includes protein bound drugs
  • competition between acids or between bases

Passive reabsorption (only a few drugs, small lipid soluble)

drug movement from renal tubule back to blood stream
  • lipid soluble drugs
  • unionized drug molecules
  • normal concentrating ability
Passive reabsorption can be reduced by disease (accidental) or by therapy (intentional)
  • increases elimination rate of the drug
  • DOES NOT WORK if reabsorption is not an important part of normal elimination
How?
  • When you manage to increase urine production by administering fluids:
    • reduced water recovery from tubule
    • concentations of EVERYTHING in urine falls
      • Diffusion "pressure" is reduced
      • Contact time with epithelium is reduced
      • More drug leaves with urine
    • IF you manage to alter urine pH
      • ionized drug cannot be reabsorbed so it leaves in the urine
      • acids trapped in alkaline urine
      • bases trapped in acid urine
      • renal elimination of aspirin can go from 2% to 30% of total elimination
Efferent blood supply of the nephron enters/leaves the glomerular tuft, then bathes the tubule/collecting duct before leaving the kidney. A PORTION of the plasma water is diverted into the nephron as it passes.

Nephron image courtesy of Blausen Medical
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