Half-Life Comparison of Oral Hydromorphone vs Oxycodone
Oral hydromorphone has a shorter half-life of 2-3 hours compared to oral oxycodone's 3-4 hour half-life, which impacts their dosing frequency and duration of action. 1, 2
Pharmacokinetic Profiles
Hydromorphone (Dilaudid)
- Half-life: 2-3 hours 1
- Time to peak plasma concentration: 0.5-1 hour 1
- Bioavailability: Approximately 24% (undergoes extensive first-pass metabolism) 1
- Metabolism: Extensively metabolized via glucuronidation in the liver
95% metabolized to hydromorphone-3-glucuronide 1
- Excretion: Primarily renal, with most excreted as hydromorphone-3-glucuronide 1
Oxycodone (OxyContin)
- Half-life: 3-4 hours 2, 3
- Time to peak plasma concentration: 1-1.5 hours 2
- Bioavailability: 60-87% (higher than hydromorphone) 2, 3
- Metabolism: Primarily hepatic
- Metabolized to noroxycodone (via CYP3A4) and oxymorphone (via CYP2D6) 2
- Excretion: Primarily renal, with free oxycodone (up to 19%) and conjugated oxycodone (up to 50%) 2
Clinical Implications of Half-Life Differences
The shorter half-life of hydromorphone has important clinical implications:
- Dosing frequency: Immediate-release hydromorphone typically requires dosing every 4 hours for optimal pain control due to its shorter half-life 4
- Breakthrough pain management: May require more frequent dosing for breakthrough pain compared to oxycodone
- Steady state: Hydromorphone reaches steady state within 24 hours, while oxycodone reaches stable plasma levels within 24 hours 3
For oxycodone:
- The slightly longer half-life allows for slightly more extended dosing intervals
- Extended-release formulations can provide 12-hour duration of action 3
Special Considerations
Renal Impairment
- Both drugs require dose adjustments in renal impairment
- Hydromorphone: Exposure increases 2-fold in moderate and 3-fold in severe renal impairment 1
- Oxycodone: Substantially excreted by kidneys, with increased risk of adverse reactions in renal impairment 2
Hepatic Impairment
- Both drugs require caution in hepatic impairment
- Hydromorphone: Exposure increases 4-fold in moderate hepatic impairment 1
- Oxycodone: Clearance may decrease in hepatic impaired patients 2
Clinical Relevance
The half-life difference between these opioids affects:
- Dosing schedules (hydromorphone may require more frequent administration)
- Duration of analgesia
- Potential for drug accumulation
- Breakthrough pain management strategies
When selecting between these medications, the half-life should be considered alongside potency, patient-specific factors, and formulation options to optimize pain management outcomes.