Article Figures & Data
Figures
- Fig. 1.
Total plasma IgE and serum NO levels in type 1 allergic mice. (A) ○, control mice; ●, sensitized mice. Each point represents the mean ± S.D. of 10–15 mice. *P < 0.01 compared with control mice. (B) At 5 and 7 days after the primary sensitization (PS5 and PS7, respectively), the mice were sacrificed. On day 8 after primary sensitization, the mice received the secondary sensitization of OVA. The mice were sacrificed at SS7. Each point represents the mean ± S.D. of 10 mice. *P < 0.01 compared with individual control mice. **P < 0.05 compared with PS5 mice.
- Fig. 2.
Changes in hepatic P450 isozyme activities in IgE-mediated allergic mice. □, control mice for PS7 and SS7; ▪▪▪, sensitized mice (PS7 and SS7 mice). Data are expressed as the mean ± S.D. of 4–6 mice. *P < 0.01 compared with each control mice. **P < 0.01 compared with PS7 mice. (A) APAP formed from 10 μM PH after a 5-minute incubation with microsomes (1 mg/ml); (B) 4-OH-TB formed from 800 μM TB after a 30-minute incubation with microsomes (0.5 mg/ml); (C) 1′-OH-BF formed from 2 μM BF after a 5-minute incubation with microsomes (0.4 mg/ml); (D) 6-OH-CHZ formed from 20 μM CHZ after a 5-minute incubation with microsomes (0.5 mg/ml); (E) 1′-OH-MDZ formed from 10 μM MDZ after a 4-minute incubation with microsomes (0.1 mg/ml).
- Fig. 3.
Hepatic protein expression of CYP1A2, 2C, 2D, 2E1 and 3A in sensitized mice. The protein expression is expressed in terms of percentage of the control mice (Cont.) on day 7 after i.p. injection of saline, with the control set to 100%. All samples were loaded in triplicate.
- Fig. 4.
Plasma concentration-time profiles of PH, APAP, IMP, and CHZ after single intravenous injection. P450 probe substrates were intravenously injected at each dose of 5 mg/kg: (A) PH (CYP1A2 substrate); (B) APAP (CYP1A2 metabolite); (C) IMP (CYP2D substrate); (D) CHZ (CYP2E1 substrate). ○, mice seven days after i.p. injection of saline (control); ●, PS7 mice; ▪▪▪, SS7 mice. Data are expressed as the mean ± S.D. (n = 4–6).
- Fig. 5.
Hepatic PH and CHZ concentrations after intravenous injection. (A) parent PH; (B) parent CHZ. Control: mice seven days after i.p. injection of saline. Data are expressed as the mean ± S.D. (n = 4–6). *P < 0.01, significantly different from control mice. ND, not detectable.
- Fig. 6.
Inhibitory effect of NO on the activities of hepatic P450 (CYP) isozymes. Hepatic microsomes were preincubated with 1 mM NOC7 or vehicle for 30 minutes at 37°C. Data are expressed as mean ± S.D. (n = 3) of the percentage of P450 isozyme activities in the absence of NOC7. *P < 0.01, significantly different from the vehicle.
- Fig. 7.
Changes in microsomal hepatic P450 (CYP) activities in type 1 allergic mice treated with carboxy-PTIO. □, mice without carboxy-PTIO treatment; ▪▪▪, mice with carboxyl-PTIO treatment. Control: seven days after i.p. injection of saline. Data are expressed as the mean ± S.D. (n = 4). *P < 0.01, significantly different from PS7 mice without carboxy-PTIO treatment.
Tables
- TABLE 1
Pharmacokinetic parameters after single i.v. injection of PH, IMP and CHZ.
Data are expressed as the mean (n = 4–6).
Substrate (or Metabolite) Parameter Control Sensitization PS7 SS7 PH λ (min−1) 0.16 ± 0.03 0.15 ± 0.03 0.14 ± 0.01 AUC (μM·min) 266.5 ± 79.1 183.0 ± 44.8 207.2 ± 31.9 T1/2 (min) 4.60 ± 1.27 4.91 ± 0.81 4.97 ± 0.37 CLtot (ml/min/kg) 113.4 ± 29.8 161.0 ± 35.2 137.9 ± 21.7 Vd (l/kg) 0.89 ± 0.26 1.19 ± 0.41 0.66 ± 0.24 APAP AUC (μM·min) 375.3 ± 16.9 166.1 ± 22.9a 216.7 ± 25.6a IMP A (nmol/ml) 2.59 ± 0.17 3.91 ± 0.45a 3.52 ± 0.73a α (min−1) 0.033 ± 0.011 0.055 ± 0.007 0.040 ± 0.009 B (nmol/ml) 1.62 ± 0.31 2.02 ± 0.85 1.48 ± 0.18 β (min−1) 0.017 ± 0.007 0.031 ± 0.011 0.022 ± 0.002 CLtot (ml/min/kg) 157.9 ± 19.5 189.0 ± 6.1 177.9 ± 14.8 AUC (μM·min) 101.7 ± 13.5 83.7 ± 2.7 89.4 ± 7.8 Vdss (l/kg)b 7.04 ± 0.57 4.47 ± 0.92a 4.72 ± 0.64a CHZ λ (min−1) 0.22 ± 0.04 0.14 ± 0.01a 0.11 ± 0.01a AUC (μM·min) 859.9 ± 124.5 1145.8 ± 57.6a 1134.6 ± 86.9a T1/2 (min) 3.16 ± 0.47 4.86 ± 0.29a 6.46 ± 0.23a CLtot (ml/min/kg) 35.1 ± 5.3 25.8 ± 1.3a 25.9 ± 1.8a Vd (l/kg) 0.13 ± 0.04 0.18 ± 0.01 0.20 ± 0.03
In this issue
Pharmacokinetics and P450 Inhibition in Type 1 Allergic Mice
