Table 1.
AEDs and their Main Mechanisms of Elimination and Susceptibility to Pharmacokinetic Interactions
| AED | Main Route of Elimination | CYP Degradation | CYP Induction | CYP Induction | UGT Degradation | UGT Induction | UGT Inhibition |
|---|---|---|---|---|---|---|---|
| Carbamazepine | Oxidation | Yes, 3A4, and epoxide hydrolase (metabolite) | Yes, CYP3A4, 2C9, 1A2 | No | No | Yes | No |
| Clobazam | Oxidation | Yes, CYP3A4 | No | No | No | No | No |
| Clonazepam | Oxidation | Yes, CYP3A4 | No | No | No | No | No |
| Eslicarbazepine acetate | Glucuronidation | No | Yes, CYP3A4 | No | Yes, but isoenzymes not identified | No | No |
| Ethosuximide | Oxidation | Yes, CYP3A4 | No | No | No | No | No |
| Felbamate | Oxidations (>50 %), renal excretion (<30 %) | Yes, CYP 3A4, 2E1 | CYP3A4* | CYP2C19 | No | No | No |
| Gabapentin | Renal excretion | No | No | No | No | No | No |
| Lacosamide | Demethylation | No | No | No | No | No | No |
| Lamotrigine | Conjugation | No | No | No | Yes, UGT1A4 | No | No |
| Levetiracetam | Hydrolysis (25 %), renal excretion (75 %) | No, type-B esterase | No | No | No | ? | No |
| Oxcarbazepine | Conjugation (>50 %), renal excretion (>30 %) | No, arylketone reductase | Yes, CYP3A4, | Yes, CYP2C19* | Yes | Yes, UGT1A4 | No |
| Phenobarbital | Oxidation/conjugation (75 %), renal excretion (25 %) | Yes, CYP2C9, 2C19, 2E1 | Yes, CYP3A4, 2C9, 1A2 | No | Yes | No | No |
| Phenytoin | Oxidation | Yes, CYP2C9, 2C19 | Yes, CYP3A4,2C9, 1A2 | Yes, CYP2C9 | No | Yes | No |
| Pregabalin | Renal excretion | No | No | No | No | No | No |
| Rufinamide | Hydrolysis, glucuronidation | No, carboxyl esterases | Yes, CYP3A4 | No | Yes | No | No |
| Stiripentol | Oxidation, hydroxylation,O-methylation, glucuronidation | No, carboxyl esterases | No | Yes, CYP 1A2, 3A4, 2C19, 2D6 | No | No | No? |
| Tiagabine | Oxidation | Yes, CYP3A4 | No | No | No | No | No |
| Topiramate | Oxidation (20-60 %), renal excretion (40-80 %) | Yes, but isoenzymes not identified | Yes, CYP3A4* (>200 mg/day) | Yes, CYP2C19* | No | No | No |
| Topiramate | Oxidation (>50 %), conjugation (30-40 (30-40 %) | Yes, 2A6, 2C9, 2C19, 2B6 and mitochondrial oxidases | No | Yes, CYP2C9, CYP3A4?, and epoxide hydrolase | Yes, UGT1A3, 2B7 | No | Yes |
| Vigabatrin | Renal excretion | No | No | No | No | No | No |
| Zonisamide | Oxidation, reduction, acetylation (>50 %), renal excretion (30 %) | Yes, CYP3A4, and N-acetyl transferase | No | No | No | No | No |
*
Weak induction or inhibition. AED=Antiepileptic drug. CYP=Cytochrome P450 enzyme, UGT=Uridine diphosphate glucuronosyltransferase enzymes.
The most commonly used AEDs are listed. Main routes of metabolism and affection of other enzymes are listed. Isoenzymes are given where they have been identified. Several sources are used, see text.