TABLE 1

Estimated parameters from the final TMDD model

Parameters (unit)DefinitionEstimate%RSEShrinkage
V2 (L)TPPU central volume of distribution0.023113
V4 (L)TCPU central volume of distribution0.015818
CL2 (L/h)TPPU clearance0.00178
CL4 (L/h)TCPU clearance0.001417
KA1 (h−1)TPPU first-order absorption rate constant0.96110
KA3 (h−1)TCPU first-order absorption rate constant0.7312
kon TPPU, R1 (nM−1h−1)TPPU second-order association rate constant to sEH0.091820
koff TPPU, R1 (h−1)TPPU first-order dissociation rate constant from sEH2.2420
kon TCPU, R1 (nM−1h−1)TCPU second-order association rate constant to sEH0.077944
koff TCPU, R1 (h−1)TCPU first-order dissociation rate constant from sEH2.6791
kon TCPU, R2 (nM−1h−1)TCPU second-order association rate constant to unknown receptor0.027596
koff TCPU, R2 (h−1)TCPU first-order dissociation rate constant from unknown receptor11.992
Rmax1 (nmol)Total sEH amount16.24
Rmax2 (nmol)Total unknown target amount46.620
2V2Variance of interindividual variability on V20.353315
2V4Variance of interindividual variability on V40.1784235
2cl2Variance of interindividual variability on V20.17462
2cl4Variance of interindividual variability on V20.3153628
2ka1Variance of interindividual variability on V20.195429
2ka3Variance of interindividual variability on V20.04595546
2koff, TCPU,R1Variance of interindividual variability on V23.746042
2 koff, TCPU,R2Variance of interindividual variability on V20.3112167
2Proportional variance of residual variability of TPPU0.0831511
ס22Proportional variance of residual variability of TCPU0.05573817
ס32Additive variance of residual variability of TPPU18.55211
ס42Additive variance of residual variability of TCPU0.03811417