Table 2.
Phenytoin Estimation of PK Parameters
| Final Model | Bootstrap (n=1000) | Published Values | |||||
|---|---|---|---|---|---|---|---|
| Parameter | Point Estimate (RSE) | IIV, CV% (RSE) | Shrinkage (%) | 2.5th Percentile | Median | 97.5th Percentile | Point Estimate (References) |
| Structural Model | |||||||
| Ka1 (1/h), fosphenytoin | 1.99 (19%) | NE | NA | 1.62 | 2.07 | 5.65 | 2.772 (56) |
| Ka2 (1/h), oral PHT for fast release | 0.459 (93%) | NE | NA | 0.24 | 0.44 | 0.53 | 0.513 (28) |
| Ka3 (1/h), oral PHT for extended release | 1.7 FIX | NE | NA | NA | NA | NA | - |
| Vmax (mg/h)* | 19.3 (7%) | 37.8 (70%) | 52 | 18.2 | 20.4 | 23.4 | 7.47 – 32.8 (22-26, 28) |
| Km (mg/L) | 5 FIX | 170 (41%) | 39 | NA | NA | NA | 2.18 – 8.15 (22-26) |
| V (L)* | 78.6 (5%) | 33.9 (26%) | 20 | 67.3 | 76.5 | 87.6 | 35 – 109.2 (28) |
| F, oral PHT | 0.859 FIX | NE | NA | NA | NA | NA | 0.859 (29) |
| Duration of zero order release (h) | 1.1 FIX | NE | NA | NA | NA | NA | - |
| Fu, unbound fraction of PHT | 0.112 (4%) | 25.8 (26%) | 21 | 0.10 | 0.11 | 0.12 | 0.12 (57) |
| Residual Variability | |||||||
| Proportional error for total and free PHT | 17.1 (4%) | NA | 22 | 14.8 | 16.9 | 19.0 | 8.6-12 (27) |
F, bioavailability; Fu, fraction unbound; Ka1, rate constant for fosphenytoin converting to phenytoin; Ka2, absorption constant for oral phenytoin fast release formulation; Ka3, absorption constant for oral phenytoin extended release formulation; Km, Michaelis constant; NA, not applicable; NE, not estimated; PHT, phenytoin; V, volume of distribution; Vmax, maximal velocity.
*
Published values of PK parameters were converted to parameter values for a 70 kg adult.