Table 3.
Lamotrigine De Novo Estimation of PK Parameters
| Study Cohort Estimates | Bootstrap (n=1000) | Rivas, et al. Study Estimates | |||||
|---|---|---|---|---|---|---|---|
| Parameters | Point Estimate (RSE) | IIV, CV% (RSE) | 2.5th Percentile | Median | 97.5th Percentile | Point Estimate (RSE) | IIV, CV% (RSE) |
| θ1 (CL), L/h/kg* | 0.0234 (11%) | 62.4% (15%) | 0.0164 | 0.0231 | 0.0295 | 0.028 (2.1%) | 27.5% (9.4%) |
| V, L/kg | 1.19 (23%) | 154.9% (15%) | 0.40 | 1.15 | 2.45 | 1.5 Fixed | NE |
| Ka, 1/h | 1.3 Fixed | NE | NA | NA | NA | 1.3 Fixed | NE |
| θ2 (VPA) | −0.713 Fixed | NA | NA | NA | NA | −0.713 (7.7%) | NA |
| θ3 (PHT) | 0.663 Fixed | NA | NA | NA | NA | 0.663 (10%) | NA |
| θ4 (PB or PRM) | 0.588 Fixed | NA | NA | NA | NA | 0.588 (8.7%) | NA |
| θ5 (CBZ) | 0.467 Fixed | NA | NA | NA | NA | 0.467 (30%) | NA |
| θ6 (IND) | 0.864 Fixed | NA | NA | NA | NA | 0.864 (12%) | NA |
| Additive residual error | 1.46 (39%) | NA | 0.31 | 1.25 | 4.14 | 1.25 (8.2%) | NA |
CBZ, carbamazepine; CL, clearance; CV, coefficient of variation; IND, 2 or more concomitant medications (inducers); Ka, absorption constant for lamotrigine; NA, not applicable; NE, not estimated; PB, phenobarbital; PRM, primidone; PHT, phenytoin; RSE, relative standard error; V, volume of distribution; VPA, valproic acid.
*
CL (L/h) = θ1 * BW * e −θ2*VPA*e θ3*PHT*e θ4*(PB or PRM)* e θ5*CBZ*e θ6*IND