Table 3.
m-f-PBPK Model Predicted Dose-Normalized Steady-State Total and Unbound Δ9-THC and 11-OH-THC Maternal (or Non-pregnant) Plasma, Umbilical Venous Plasma and Fetal Brain Concentrations at 15, 25, and 40 GW of Pregnancy after Daily Oral Cannabis Use
| Oral | ||||||||
|---|---|---|---|---|---|---|---|---|
| Δ9-THC | 11-OH-THC | |||||||
| Non-Pregnant | GW15 | GW25 | GW40 | Non-Pregnant | GW15 | GW25 | GW40 | |
| MP or NP Css,avg (nM/mg dose) | 0.13 | 0.11 | 0.10 | 0.093 | 0.18 | 0.17 | 0.17 | 0.17 |
| MP or NP Css,avg,u (nM/mg dose) | 0.0014 | 0.0012 | 0.0011 | 0.0010 | 0.0021 | 0.0021 | 0.0021 | 0.0021 |
| MP or NP Css,max (nM/mg dose) | 0.68 | 0.57 | 0.55 | 0.49 | 0.80 | 0.78 | 0.78 | 0.78 |
| MP or NP Css,max,u (nM/mg dose) | 0.0075 | 0.0063 | 0.0060 | 0.0054 | 0.0096 | 0.0093 | 0.0093 | 0.0093 |
| UVP Css,avg (nM/mg dose) | NA | 0.049 | 0.034 | 0.025 | NA | 0.26 | 0.21 | 0.17 |
| UVP/MP Css,avgR | NA | 0.44 | 0.33 | 0.27 | NA | 1.51 | 1.20 | 0.98 |
| UVP Css,avg,u (nM/mg dose) | NA | 0.0003 | 0.0002 | 0.0002 | NA | 0.0018 | 0.0014 | 0.0011 |
| UVP/MP Css,avg,uR | NA | 0.28 | 0.21 | 0.18 | NA | 0.84 | 0.67 | 0.55 |
| UVP Css,max (nM/mg dose) | NA | 0.28 | 0.14 | 0.10 | NA | 1.16 | 0.43 | 0.29 |
| UVP Css,max,u (nM/mg dose) | NA | 0.0020 | 0.0010 | 0.0007 | NA | 0.0077 | 0.0029 | 0.0020 |
| Fetal Brain Css,avg (nM/mg dose) | NA | 0.073 | 0.048 | 0.031 | NA | 0.89 | 0.69 | 0.54 |
| Fetal Brain/MP Css,avgR | NA | 0.66 | 0.46 | 0.33 | NA | 5.08 | 4.00 | 3.16 |
| Fetal Brain/UVP Css,avgR | NA | 1.50 | 1.40 | 1.22 | NA | 3.36 | 3.32 | 3.16 |
| Fetal Brain Css,avg,u (nM/mg dose) | NA | 0.0003 | 0.0002 | 0.0001 | NA | 0.0017 | 0.0013 | 0.0010 |
| Fetal Brain/MP Css,avg,uR | NA | 0.23 | 0.16 | 0.12 | NA | 0.81 | 0.64 | 0.51 |
| Fetal Brain/UVP Css,avg,uR | NA | 0.81 | 0.76 | 0.66 | NA | 0.96 | 0.95 | 0.92 |
| Fetal Brain Css,max (nM/mg dose) | NA | 0.39 | 0.15 | 0.077 | NA | 3.80 | 1.35 | 0.84 |
| Fetal Brain Css,max,u (nM/mg dose) | NA | 0.0015 | 0.0006 | 0.0003 | NA | 0.0074 | 0.0026 | 0.0016 |
NA: not applicable; MP: maternal plasma; NP: Non-pregnant plasma; UVP: umbilical venous plasma; Css,avg: average steady-state concentration; Css,avg,u: unbound average steady-state concentration; Css,max: maximum steady-state concentration; Css,max,u: unbound maximum steady-state concentration; Css,avgR: ratio of average steady-state concentration; Css,avg,uR: ratio of unbound average steady-state concentration; Δ9-THC: 1 nM = 0.314 ng/mL; 11-OH-THC: 1 nM = 0.330 ng/mL.