FRCA Notes

Ibuprofen and Other Non-Specific COX Inhibitors

  • A propionic acid derivative with a chiral centre

Presentation

  • Presents as a racemic mixture of:
    • The active S-enantiomer dexibuprofen
    • The inactive R-enantiomer, which is converted by an isomerase in the gut/liver to the active S-enantiomer

  • Forms:
    • Tablets/oral suspension
    • 5% gel for topical administration
    • IV preparation
    • A modified release oral preparation is available for use in inflammatory disorders

  • Adult dosing:
    • Typically 400mg TDS PO
    • Short-term high dose therapy can be used e.g. 600mg TDS for 3 days following LSCS

Pharmacokinetics

  • Rapidly absorbed from the gut - oral bioavailability >80%
  • 99% plasma protein (albumin) bound
  • Metabolised by CYP450 enzymes to inactive hydroxy and carboxy metabolites (although a small amount undergoes glucuronidation)
  • Elimination half-life 2-3hrs
  • Excretion is 100% renal

Pharmacodynamics

  • Lower dosing is not associated with prothrombotic events as with other NSAIDs
  • Generally lowest incidence of side-effects than the other NSAIDs
  • However, has a weaker anti-inflammatory effect; at <1.2g/day may not be effective in chronic inflammatory disease

  • A pyrazalone with potent anti-inflammatory
  • However has serious haematological side-effects: agranulocytosis and aplastic anaemia
  • Significantly plasma protein bound and therefore interacts with other highly protein bound drugs
  • Other side-effects include rash, impaired hepatic function and sodium/water retention

  • A non-specific oxicam with many features in common with other NSAIDs
  • Pharmacokinetic benefits:
    • Can be given IV therefore rapid onset of action; also high oral bioavailability
    • Has an elimination half life of 72hrs, therefore long duration and once-daily (20mg) dosing
  • 99% protein bound
  • Metabolised to an inactive metabolite
  • Excreted via urine (66%) and bile (33%)