Table 2.
Pharmacological properties of cenobamate a.
| Dosage forms and strengths (mg) | 12.5, 25, 50, 100, 150, 200 | |
| Bioavailability | 88%, not influenced by high-fat meal | |
| Peak plasma time: | 1–4 h | |
| Volume distribution | 40–50 L | |
| Plasma-protein binding | 60%, primarily to albumin | |
| Metabolism | Glucuronidation (UGT2B7 > UGT2B4) Oxidation (CYP2E1, CYP2A6, CYP2B6 > CYP2C19, CYP3A4/5) |
|
| Elimination half-life (hours) | Human | 50–60 |
| Rat | 2.9 | |
| Mice | NA | |
| Oral clearance | 0.45–9.63 L/hr | |
| Excretion | Renal 87.8% (6% unmetabolized) and feces 5.2% (<1% unmetabolized) | |
| Physicochemical properties extracted from SwissADME b | ||
| Formula | C10H10ClN5O2 | |
| Molecular weight (150–500 g/mol) | 267.67 g/mol | |
| Fraction Csp3 (0.25–1.0) | 0.20 | |
| Num. rotatable bonds (0–9) | 5 | |
| Num. H-bond acceptors (≤10) | 5 | |
| Num. H-bond donors (≤5) | 1 | |
| Topological polar surface area (20–130 Å2) | 95.92 Å2 | |
| Lipophilicity | ||
| Consensus Log Po/w (0.7–5.0) | 0.95 | |
| Water solubility | ||
| Log S (ESOL) (−6–0) | −2.59 | |
| Class | Soluble | |
| Pharmacokinetics | ||
| Gastrointestinal absorption | High | |
| Blood–brain barrier permeant | No | |
| Druglikeness | ||
| Bioavailability score | 0.55 | |
| Medicinal chemistry | ||
| Synthetic accessibility [1(very easy)–10 (very difficult)] |
3.05 | |
Abbreviations: NA, not available/not reported. a https://www.xcopri.com (accessed on 30 May 2023). b Normal range provided is desirable for oral drugs. Consensus Log Po/w is the average of iLOGP, XLOGP3, WLOGP, MLOGP, and SILICOS-IT.