TABLE 4

Effects of PCN and 3-MC on PK parameters of individual drugs and metabolites

Data were fit to a noncompartmental PK model. Values represent means ± S.D. generated from six mice.

TreatmentCmaxbAUC0→∞cExtrapt1/2CL/FVz/F
%hl/hliters
Substrate
 MDZControl173.0 ± 53.7321.5 ± 51.021.931.36 ± 0.270.288 ± 0.0510.558 ± 0.113
PCNa16.06 ± 13.4*13.1 ± 3.71.240.52a 3.8 × 10−51.8 × 103
3-MC56.90 ± 11.8*74.6 ± 32.5*13.120.867 ± 0.274**1.26 ± 0.45***1.51 ± 0.63**
 PHEControl425.8 ± 256.9154.4 ± 93.318.370.466 ± 0.1373.74 ± 1.572.52 ± 1.47
PCN550.0 ± 386.2150.1 ± 68.410.640.155 ± 0.044***3.24 ± 1.590.761 ± 0.589
3-MCa72.04.60.01NDNDND
 DXMControl237.2 ± 88.2646.9 ± 137.625.441.39 ± 0.3639.6 ± 12.3122 ± 85
PCN143.4 ± 60.6213.0 ± 36.4***30.841.09 ± 0.47158 ± 57220 ± 53
3-MC154.5 ± 97.942.3 ± 82.5***27.141.20 ± 0.81169 ± 121206 ± 70
 DICControl49.15 ± 13.9945.23 ± 14.391.780.418 ± 0.0431.37 ± 0.970.797 ± 0.504
PCN6.592 ± 2.613*7.23 ± 2.81*12.320.979 ± 0.410**2.05 ± 1.342.38 ± 1.17***
3-MC29.75 ± 9.12**17.20 ± 4.8*9.591.03 ± 0.33**0.616 ± 0.3900.801 ± 0.290
 CLZControl199.0 ± 61.9153.3 ± 43.50.940.380 ± 0.0621.93 ± 1.220.999 ± 0.565
PCN23.25 ± 6.91*16.6 ± 4.9*4.090.732 ± 0.3144.02 ± 2.743.96 ± 2.02
3-MC4.645 ± 1.138*3.18 ± 0.91*7.091.04 ± 0.401***9.06 ± 5.63**11.6 ± 5.2*
Metabolite
 1′-OH-MDZControl4.540 ± 0.44911.88 ± 9.5632.671.48 ± 0.88
PCN1.950 ± 0.528**1.81 ± 0.38**6.660.672 ± 0.276
3-MC3.532 ± 0.616**7.46 ± 1.6922.811.29 ± 0.43
 APAPControl523.6 ± 190.8671.6 ± 237.68.590.820 ± 0.233
PCN623.3 ± 140.5367.8 ± 70.7**1.850.467 ± 0.172**
3-MC336.8 ± 139.0225.8 ± 62.7***3.810.702 ± 0.227
 DXOControl29.9 ± 14.856.3 ± 10.315.561.17 ± 0.38
PCN15.8 ± 6.326.1 ± 8.7***52.301.16 ± 0.43
3-MC14.6 ± 9.620.8 ± 46.5***18.660.376 ± 0.181
 4′-OH-DICControl240.2 ± 90.0631.1 ± 250.232.761.85 ± 0.34
PCN747.5 ± 435.2**315.6 ± 133.9**14.771.28 ± 0.49
3-MC173.3 ± 61.0362.4 ± 151.743.102.56 ± 1.19
 6-OH-CLZControl60.7 ± 51.831.9 ± 12.812.240.422 ± 0.135
PCNa458.4 ± 134.1*171.1*0.010.357a
3-MC33.7 ± 10.921.6 ± 2.837.700.620 ± 0.049
  • Extrap, extrapolated contribution to AUC; ND, not determined due to insufficient data points representing the elimination phase.

  • a Given incomplete data points because some were below quantification limits, a sparse data model was used.

  • b Values are given in nM for MDZ, PHE, DXM, APAP, DXO, 4′-OH-DIC, and 6-OH-CLZ and in µM for DIC, CLZ, and 1′-OH-MDZ.

  • c Values are given in nM·h for MDZ, PHE, DXM, APAP, DXO, 4′-OH-DIC, and 6-OH-CLZ and in µM·h for DIC, CLZ, and 1′-OH-MDZ.

  • * P < 0.001; **P < 0.05; ***P < 0.01 compared with the control (one-way analysis of variance with Bonferroni post hoc tests).