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Clinical Pharmacokinetics

, Volume 42, Issue 12, pp 1023–1042 | Cite as

Clinical Pharmacokinetics of Oxcarbazepine

  • Theodor W. MayEmail author
  • Elisabeth Korn-Merker
  • Bernhard Rambeck
Review Article

Abstract

Oxcarbazepine is an antiepileptic drug with a chemical structure similar to carbamazepine, but with different metabolism. Oxcarbazepine is rapidly reduced to 10, 11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD), the clinically relevant metabolite of oxcarbazepine. MHD has (S)-(+)- and the (R)-(−)-enantiomer, but the pharmacokinetics of the racemate are usually reported.

The bioavailability of the oral formulation of oxcarbazepine is high (>95%). It is rapidly absorbed after oral administration, reaching peak concentrations within about 1–3 hours after a single dose, whereas the peak of MHD occurs within 4–12 hours. At steady state, the peak of MHD occurs about 2–4 hours after drug intake.

The plasma protein binding of MHD is about 40%. Cerebrospinal fluid concentrations of MHD are in the same range as unbound plasma concentrations of MHD. Oxcarbazepine can be transferred significantly through the placenta in humans.

Oxcarbazepine and MHD exhibit linear pharmaco-kinetics and no autoinduction occurs. Elimination half-lives in healthy volunteers are 1–5 hours for oxcarbazepine and 7–20 hours for MHD. Longer and shorter elimination half-lives have been reported in elderly volunteers and children, respectively. Mild to moderate hepatic impairment does not appear to affect MHD pharmacokinetics. Renal impairment affects the pharmacokinetics of oxcarbazepine and MHD.

The interaction potential of oxcarbazepine is relatively low. However, enzyme-inducing antiepileptic drugs such as phenytoin, phenobarbital or carbamazepine can reduce slightly the concentrations of MHD. Verapamil may moderately decrease MHD concentrations, but this effect is probably without clinical relevance.

The influence of oxcarbazepine on other antiepileptic drugs is not clinically relevant in most cases. However, oxcarbazepine appears to increase concentrations of phenytoin and to decrease trough concentrations of lamotrigine and topiramate. Oxcarbazepine lowers concentrations of ethinylestra-diol and levonorgestrel, and women treated with oxcarbazepine should consider additional contraceptive measures. Due to the absent or lower enzyme-inducing effect of oxcarbazepine, switching from carbamazepine to oxcarbazepine can result in increased serum concentrations of comedication, sometimes associated with adverse effects.

The effect of oxcarbazepine appears to be related to dose and to serum concentrations of MHD. In general, daily fluctuations of MHD concentration are relatively slight, smaller than would be expected from the elimination half-life of MHD. However, relatively high fluctuations can be observed in individual patients. Therapeutic monitoring may help to decide whether adverse effects are dependent on MHD concentrations. A mean therapeutic range of 15–35 mg/L for MHD seems to be appropriate. However, more systematic studies exploring the concentration-effect relationship are required.

Keywords

Carbamazepine Valproate Antiepileptic Drug Lamotrigine Felodipine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

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Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  • Theodor W. May
    • 1
    Email author
  • Elisabeth Korn-Merker
    • 2
  • Bernhard Rambeck
    • 1
  1. 1.Department of BiochemistryEpilepsy Research FoundationBielefeldGermany
  2. 2.Epilepsy Centre BethelClinic KidronBielefeldGermany

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