Estimated parameters from modeling using model I and II
| Parameter | Unit | Definition | Estimated Value | ||
|---|---|---|---|---|---|
| CYP1A1 Only (%CV) | CYP1A1 + CYP1A2 (%CV) | ||||
| BNF plasma PK | Vmax | ml/(min · kg) | Plasma BNF clearance under conditions of maximal CYP1A induction | 329.7 (58.3) | 331.9 (57.7) |
| Km | pmol/(min · mg protein) | CYP1A activity at which plasma clearance is half of the Vmax | 447.7 (112) | 563.3 (97.6) | |
| Vp | ml/kg | Volume of distribution | 5041 (31.9) | 5316 (44.9) | |
| CYP1A1 mRNA | kin, R1 | (copy/ng total RNA) · min−1 | Baseline zero-order CYP1A1 mRNA transcription rate constant | 4.02 × 10−2 (37.7) | 3.42 × 10−2 (41.6) |
| kout, R1 | min−1 | First-order CYP1A1 mRNA degradation rate constant | 7.24 × 10−3 | 6.16 × 10−3 | |
| SR1 | (ng/ml)−1 | Proportionality coefficient between plasma BNF concentration and CYP1A1 mRNA induction | 4.1 (27.2) | 5.3 (23.0) | |
| t1/2, 1A1 | H | CYP1A1 mRNA degradation half-life | 1.6 | 1.9 | |
| CYP1A2 mRNA | kin, R2 | (copy/ng total RNA) · min−1 | Baseline zero-order CYP1A2 mRNA transcription rate constant | 52.4 (31.2) | |
| kout, R2 | min−1 | First-order CYP1A2 mRNA degradation rate constant | 8.27 × 10−3 | ||
| SR2 | (ng/ml)−1 | Proportionality coefficient between plasma BNF concentration and CYP1A2 mRNA induction | 2.13 × 10−2 (14.9) | ||
| t1/2, 1A2 | H | CYP1A2 mRNA degradation half-life | 1.4 | ||
| CYP1A (EROD) | kin, E1 | (pmol/min/mg protein) · min−1 | Baseline zero-order EROD production rate constant contributed by CYP1A1 mRNA | 2.65 × 10−3 (18.6) | 1.6 × 10−3 (15.9) |
| kin, E2 | (pmol/min/mg protein) · min−1 | Baseline zero-order EROD production rate constant contributed by CYP1A2 mRNA | 8.57 × 10−2 | ||
| kin | (pmol/min/mg protein) · min−1 | Baseline zero-order EROD production rate constant | 8.73 × 10−2 | 8.73 × 10−2 | |
| kout | min−1 | First-order EROD degradation rate constant | 6.11 × 10−4 (fixed) | ||
| t1/2, EROD | h | EROD degradation half-life | 18.9 (fixed) | ||
PK, pharmacokinetics.