Table 2.
Pharmacokinetic parameters of oral antiseizure drugs.
| Medication | pKa | Lipophilicity (LogP) | Intestinal Metabolism | Active Transport Pumps | Enterohepatic Recirculation | Approximate Bioavailability/Site of Absorption | Impact of Food on Absorption | May be Largely Affected by Malabsorptive Procedures |
|---|---|---|---|---|---|---|---|---|
| Carbamazepine [32], [33], [34], [35], [36] | 16.0, −3.8 | 2.7 | Substrate CYP3A4 (to active metabolite carbamazepine-10,11-epoxide) | – | Yes | 70 – 79% | None with slow release formulation | Yes |
| Felbamate [32], [37], [38] | 14.9 | 0.6 | Substrate of CYP2C19, CYP3A4, CYP2E1 (inactive metabolites) | – | – | 90%, Small intestine | None with tablet. Suspension unknown | Yes |
| Gabapentin [32], [39], [40], [41] | 4.6, 9.9 | −1.9 | – | L amino transport protein | – | 60%, Absorption decreases with increased dose | Slight increase in absorption with food | Yes |
| Lacosamide [32], [42], [43], [44], [45], [46] | 12.5, −1.5 | 0.2 | Substrate of CYP2C9, CYP2C19, CYP3A4 (inactive metabolites) | – | – | 100% | None | Yes |
| Lamotrigine [32], [47], [48] | 14.9, 5.87 | 1.9 | Substrate of UGT1A4 and UGT2B7 | ABCB1, SLC22A1. P-gp | – | 98% | None | Yes |
| Levetiracetam [32], [49], [50], [51] | 16.1, −1.6 | −0.6 | – | – | – | 100% | May delay absorption by 0.5 hours, but extent is not affected | No |
| Oxcarbazepine [32], [52], [53] | 13.2, −4.3 | 1.8 | Substrate of CYP3A4 and UGT to 10-Hydroxy-10, 11-dihydro carbazepine | – | Possible | ≥95% | None | Yes |
| Phenobarbital [32], [54], [55] | 7.14 | 1.4 | Substrate of CYP2C9, CYP2C19, CYP2E1 | – | Yes | ≥95% | Unknown | Yes |
| Phenytoin [24], [32], [56], [57] | 9.5, −9 | 2.3 | Substrate of CYP2C9, CYP2C19 | – | Yes | 80% | Increased absorption/no change with food Caution with tube feeds |
Yes |
| Topiramate [32], [58], [59], [60] | 11, −3.7 | −0.6 | – | – | – | 80–90% | None | No |
| Valproic Acid [32], [61], [62], [63] | 5.14 | 2.5 | UGT1A3, UGT1A4, UGT1A6, UGT1A8, UGT1A9, UGT1A10, UGT2B7, and UGT2B15 Substrate of CYP2C9, CYP2A6, and to a lesser extent by CYP2B6 Metabolite activity unknown |
– | Yes | 90% | None | Yes |
Abbreviations: CYP: Cytochrome, UGT: Urindinediphosphate, glucoronosyltransferases, ABC: ATP-binding cassette protein B1, SLC: solute carrier family 22, member 1 PgP: P-glycopreotein.