Effect Timings
- Onset of Action: ~30 seconds:
- Rapid uptake by lipophilic tissue of CNS from the plasma
- Duration of Action (following bolus): ~10 minutes:
- Short duration primarily due to fall in plasma levels as it redistributes to vessel rich and lipid rich tissues (redistribution half-life 2-4 minutes)
- Context Sensitive Half-life: maximum value ~20 mins
- Low value makes it a good agent for TIVA
Absorption
- Bioavailability:
- Low oral bioavailability (<3%)
- Caused by a high first-pass effect and high hepatic extraction rate (90%)
Distribution
- Protein Binding: 98% plasma protein bound (albumin)
- Volume of Distribution (Vd): ~10 minutes:
- Short duration primarily due to fall in plasma levels as it redistributes to vessel rich and lipid rich tissues (redistribution half-life 2-4 minutes)
Metabolism
- Primarily hepatically metabolised
- 40% conjugation to a glucuronide
- 60% sulphation to a quinol
- Not significantly impacted by moderate hepatic impairment
- Likely some additional extra-hepatic metabolism
- All metabolites inactive
Elimination
- Clearance: 30-60 ml/min/kg
- Metabolites excreted by the Kidney
- Terminal Elimination Half-life: 5-12 hours:
- Plays little to no role in offset of action following bolus