Half-Life of Trileptal (Oxcarbazepine)
The half-life of oxcarbazepine itself is approximately 2 hours, but its active metabolite MHD (10-monohydroxy derivative), which is responsible for the drug's therapeutic effect, has a half-life of approximately 9 hours in adults. 1
Parent Drug vs. Active Metabolite
- Oxcarbazepine (parent compound) is rapidly reduced by cytosolic enzymes in the liver and has an elimination half-life of only 1-2 hours 1, 2
- MHD (monohydroxy derivative), the pharmacologically active metabolite, has a half-life of approximately 9 hours in adults, with a range of 7-20 hours reported across different populations 1, 2
- The FDA label specifically states the parent drug half-life is about 2 hours while MHD is about 9 hours 1
Clinical Implications of Half-Life
- Steady-state concentrations of MHD are reached within 2-3 days when oxcarbazepine is administered twice daily 1
- The 9-hour half-life of MHD allows for twice-daily dosing rather than requiring more frequent administration 3, 2
- At steady state, MHD displays linear pharmacokinetics at doses ranging from 300 to 2400 mg/day 1
Age-Related Variations
Pediatric Patients
- Children have shorter elimination half-lives than adults due to higher weight-adjusted clearance 1, 2
- Children aged 2 to <4 years have approximately 80% higher weight-adjusted clearance than adults, resulting in about half the MHD exposure 1
- Children aged 4-12 years have approximately 40% higher clearance than adults, resulting in about three-quarters the MHD exposure 1
Elderly Patients
- Elderly volunteers (60-82 years) show 30-60% higher maximum plasma concentrations and AUC values of MHD compared to younger volunteers (18-32 years) 1
- This difference is primarily due to age-related reductions in creatinine clearance rather than changes in hepatic metabolism 1
- Longer elimination half-lives have been reported in elderly volunteers 2
Special Population Considerations
Renal Impairment
- In patients with creatinine clearance <30 mL/min, the elimination half-life of MHD is prolonged to 19 hours with a 2-fold increase in AUC 1, 4
- These patients require dose reduction of at least 50% and prolonged titration periods 1, 4
Hepatic Impairment
- Mild-to-moderate hepatic impairment does not affect the pharmacokinetics of oxcarbazepine or MHD 1, 4, 2
Pregnancy
- Due to physiological changes during pregnancy, MHD plasma levels may gradually decrease throughout pregnancy 1
Dosing Frequency Rationale
- The 9-hour half-life of MHD makes twice-daily administration appropriate and effective 1, 3
- Daily fluctuations of MHD concentration are relatively slight, smaller than would be expected from the elimination half-life alone 2
- However, relatively high fluctuations can occur in individual patients, making therapeutic drug monitoring potentially useful 2