Table 4.
Plasma CEM Toxicokinetic Parameter Estimates Following Dermal Application of CEM to B6C3F1 micea
| Parameter | 300 mg/kg | 450 mg/kg | 600 mg/kg | ||
|---|---|---|---|---|---|
| Male | Female | Male | Male | Female | |
| Absorption half-life (min) | 6.07 + 6.05 | 5.06 + 3.46 | 7.00 + 3.56 | 7.55 + 4.56 | 7.71 + 2.93 |
| Cmax (predicted) (μg/mL) | 2.42 + 0.50 | 5.58 + 0.92 | 4.11 + 0.50 | 12.3 + 2.1 | 15.5 + 1.8 |
| Tmax (predicted) (min) | 11.9 + 3.7 | 9.36 + 2.01 | 13.7 + 2.3 | 14.6 + 3.1 | 14.1 + 1.8 |
| V1/F (mL/kg) | 60,700 + 40,400 | 25,000 + 10,800 | 53,500 + 18,300 | 23,700 + 9400 | 17,900 + 4600 |
| V2/F (mL/kg) | 154,000 + 612,000 | 10,600 + 5100 | 80,600 + 427,000 | 6470 + 33,200 | 3730+2210 |
| Cl/F (mL min−1 kg−1) | 3080 + 970 | 1960+260 | 2590 +480 | 1150 +180 | 959 + 98 |
| k10 half-life (min) | 13.7 + 10.7 | 8.87 + 3.30 | 14.3+ 6.0 | 14.2 + 4.6 | 12.9+ 2.5 |
| t½α (min) | 11.4 + 7.0 | 8.41 + 3.18 | 13.2 + 3.9 | 13.9 + 4.2 | 12.7 + 2.4 |
| t½β (min) | 224 + 645 | 82.4 + 39.7 | 284 +1010 | 198+734 | 153 + 79 |
| AUC∞ (predicted) (μg mL−1 min) | 97.5 + 30.6 | 153 + 20 | 174 + 32 | 520 + 80 | 626 + 64 |
| AUC∞, (predicted)/Dose (μg min mL−1 kg mg−1) | 0.325 + 0.102 | 0.510 + 0.067 | 0.387 + 0.071 | 0.867 + 0.133 | 1.04 + 0.11 |
a
Based on a two-compartment model with first order input, first order elimination, and 1/Yhat2 weighting.