Table 2.
Physicochemical, biopharmaceutical and pharmacokinetic properties of the selected pharmacological probes.
| Property | Lacosamide | Pregabalin | Tapentadol |
|---|---|---|---|
| MW (g/Mol) | 250.30 | 159.23 | 221.34 |
| Solubility (g/L) | 0.465 a | >30 b | 1.16 c |
| Lipophilicity (Log P) | 0.728 d | −1.35 | 2.87 |
| pKa | >12 e | 4.2//10.6 | 9.6//10.28 |
| BCS class | I | I | I |
| Bioavailability (%) | ≈100 | >90% | 32% |
| Fu | >0.85 | 1 | ≈0.8 |
| CL (L/h) | 1.92 # | 4.02–4.85 | 91.8 |
| V (L) | 42 # | 39.2 # | 540 |
| Unaltered fraction in urine | 0.4 | 1 | 0.03 |
| Metabolism | CYP2C9, CYP2C19 and CYP3A4 Relative contribution of each CYP still unknown |
- | 70% conjugation 13% CYP2C9 and CYP2C19 2% CYP2D6 |
| CNS data | Concentration ratio: CSF/Serum † 0.85 f,, 0.641 g Brain/Plasma * 0.553 h |
Concentration ratio: CSF/Plasma * ≈0.1 i |
Concentration ratio: Brain/Plasma * ≈4 j |
# For a 70 kg body weight; † human data, * rat data. Abbreviations: MW, molecular weight; BCS class, Biopharmaceutical Classification System; Fu, fraction unbound; Cl, clearance; V, volume of distribution; CNS, central nervous system; CSF, cerebral spinal fluid. Source: Summary of Product Characteristics and drug label. Otherwise: a Predicted using ALOGPS, Virtual Computational Chemistry Laboratory, 2005; b Chemistry review, FDA Center for Drug Evaluation and Research, application number: 22–488; c predicted using Estimation Program Interface (EPI) Suite, US EPA; d ACD/Labs; e Chemistry review, FDA Center for Drug Evaluation and Research, application number: 22–255; f May et al. (2015) [34]; g Michelhaugh et al. 2015 [35]; h Koo et al. (2011) [36]; i Feng et al. (2001) [37]; j Schröder et al. (2011) [38].