TABLE 1

Determination of interaction kinetics based on linear static model and nonlinear dynamic model

Interassay mean and S.E.M. are given (N = 2–4), except for CYP3A7, for which only N = 1 was done. Low clearance cases with an associated CV above 80% are described as not converged (n.c.) and labeled in gray and italic.

Kinetic Values at 100% e.r.Interaction Kinetics Based on Linear Static ModelInteraction Kinetics Based on Dynamic Nonlinear Model
P450Test itemKm (µM)Vmax (pmol/pmol P450/min)Km (µM)Vmax (pmol/pmol P450/min)Ki (µM)Km (µM)Vmax (pmol/pmol P450/min)Ki (µM)
1A1R-PZQ9.6 ± 2.146 ± 97.8 ± 1.631 ± 3n.c.6.8 ± 4.325 ± 623 ± 7
S-PZQn.c.80 ± 53n.c.n.c.29 ± 025 ± 835 ± 2725 ± 3
2C9R-PZQ40 ± 25130 ± 9046 ± 10144 ± 1333 ± 1530 ± 377 ± 831 ± 8
S-PZQ25 ± 837 ± 1524 ± 334 ± 736 ± 1916 ± 420 ± 622 ± 5
2C19R-PZQ7.4 ± 1.442 ± 98.4 ± 1.069 ± 206.9 ± 0.66.4 ± 1.540 ± 59.4 ± 0.4
S-PZQ1.1 ± 0.18.9 ± 0.62.7 ± 0.623 ± 43.0 ± 1.12.8 ± 0.417 ± 12.4 ± 0.7
3A4R-PZQ22 ± 460 ± 1430 ± 2051 ± 3429 ± 1025 ± 1442 ± 2818 ± 6
S-PZQ26 ± 1278 ± 4224 ± 663 ± 621 ± 824 ± 836 ± 1421 ± 2
3A5R-PZQ57 ± 2192 ± 4020 ± 434 ± 639 ± 2422 ± 128 ± 127 ± 6
S-PZQ69 ± 28127 ± 4924 ± 247 ± 627 ± 419 ± 532 ± 415 ± 1
3A7R-PZQn.c.n.c.n.c.n.c.n.c.n.c.n.c.153
S-PZQ8.14.520997n.c.17875n.c.