TABLE 2

Toxicokinetic parameters of plasma NA and NA-GSH in Cyp2abfgs-null, CYP2A13/2F1-humanized, Cyp2abfgs-null-and-LCN, and CYP2A13/2F1-humanized-and-LCN mice

Data from Fig. 2 are used for calculation of various toxicokinetic parameters. Results are presented as means ± S.D. (n = 3 to 4 per group).

AnalyteStrainAUC0–20ht1/2CL/FCmax
µg ⋅ min/mlminml/minng/ml
NACyp2abfgs-null4.2 ± 0.93.5 ± 1.472.3 ± 17.780.3 ± 26.5
CYP2A13/2F1-humanized4.6 ± 3.93.2 ± 1.1122 ± 7867.6 ± 20.2
Cyp2abfgs-null-and-LCN280 ± 40a43 ± 111.1 ± 0.3b226 ± 43a
CYP2A13/2F1-humanized-and-LCN170 ± 20c,d57 ± 391.9 ± 0.2c192 ± 49c
NA-GSHCyp2abfgs-null5.2 ± 1.1N/AN/A48.0 ± 20.1
CYP2A13/2F1-humanized3.2 ± 2.6N/AN/A51.6 ± 18.4
Cyp2abfgs-null-and-LCN30 ± 4bN/AN/A38.8 ± 5.7
CYP2A13/2F1-humanized-and-LCN26 ± 8eN/AN/A25.7 ± 14.3
  • CL, clearance; N/A, not applicable; t1/2, elimination half-life.

  • a P < 0.0001, compared with Cyp2abfgs-null mice.

  • b P < 0.05, compared with Cyp2abfgs-null mice.

  • c P < 0.0001, compared with CYP2A13/2F1-humanized mice.

  • d P < 0.001, compared with Cyp2abfgs-null-and-LCN mice.

  • e P < 0.05, compared with CYP2A13/2F1-humanized mice.