Table 3.
Plasma CEM Toxicokinetic Parameter Estimates Following Dermal Application of CEM to F344 Ratsa
| Parameter | 100 mg/kg | 200 mg/kg | 400 mg/kg | |||
|---|---|---|---|---|---|---|
| Male | Female | Male | Female | Male | Female | |
| Absorption half-life (min) | 4.67 + 2.37 | 8.06 + 7.98 | 5.10+ 1.89 | 11.8 + 10.0 | 10.1 + 3.8 | 7.50 + 3.08 |
| Cmax (predicted) (ĝ/mL) | 5.26 + 0.68 | 9.41 + 1.48 | 7.92 + 0.87 | 9.97 + 1.24 | 12.2 + 1.7 | 15.0 + 2.2 |
| Tmax (predicted) (min) | 14.1 + 3.8 | 15.2 + 3.4 | 15.0 + 3.2 | 20.9 + 3.4 | 31.7 + 6.9 | 27.2 + 6.9 |
| V1/F (mL/kg) | 13,000+3100 | 5020+3900 | 17,000 + 2900 | 8950 + 6460 | 23,100 + 5000 | 20,500 + 4300 |
| V2/F (mL/kg) | 6630+1930 | 2590+1170 | 44,300 + 30,100 | 4070 +1840 | 21,700 + 14,900 | 9520+3710 |
| Cl/F (mL min−1 kg−1) | 312 + 34 | 223 + 31 | 403 + 42 | 321 + 43 | 239 + 33 | 188 + 25 |
| k10 half-life (min) | 28.9 + 5.6 | 15.6 + 11.3 | 29.2 + 3.2 | 19.4 + 13.5 | 66.8 + 7.7 | 75.8 + 8.8 |
| t½α (min) | 24.9 + 5.6 | 13.5 + 10.8 | 26.1 + 2.7 | 17.6 + 13.0 | 62.2 + 6.8 | 70.4 + 8.5 |
| t½β (min) | 135 + 40 | 75.7 + 29.3 | 729 + 348 | 114 + 40 | 973 + 501 | 570+205 |
| AUC∞ (predicted)(μg mL−1 min) | 320 + 35 | 448 + 63 | 496 + 52 | 624 + 84 | 1670+230 | 2130 +280 |
| AUC∞ (predicted)/Dose (μg min mL−1 kg mg−1) | 3.20 + 0.35 | 4.48 + 0.63 | 2.48 + 0.26 | 3.12 + 0.42 | 4.2 + 0.6 | 5.3 + 0.7 |
a
Based on a two-compartment model with first order input, first order elimination, and 1/Yhat2 weighting. Estimate ± SE.