Comparison of the degrees of interactions between several paired drugs in various species using different dosing regimens
| Substrate | Inhibitor or Inducer | Change of AUC | Dosing Regimen | Species | Reference |
|---|---|---|---|---|---|
| MDZ | KTZ | 16-fold increase | 3 doses of 200 mg KTZ every 12 h, p.o.; 90 min after last dose of KTZ, 6 mg MDZ plus 200 mg KTZ, p.o. | Humans | Tsunoda et al., 1999 |
| 7.7-fold increase | 200 mg KTZ for 12 days, p.o.; 1 h after the last dose of KTZ, 10 mg MDZ, p.o. | Humans | Lam et al., 2003 | ||
| 5.0-fold increase | 200 mg KTZ, p.o.; 2 h later, 2 mg MDZ, p.o. | Humans | McCrea et al., 1999 | ||
| 6.5-fold increase | 10 mg/kg KTZ, i.p.; 30 min later, 15 mg/kg MDZ, i.g.; 180 min later, 5 mg/kg KTZ, i.p., to maintain serum KTZ concentrations at ≥2 μg/ml | Sprague-Dawley rats | Kotegawa et al., 2002 | ||
| 1.5-fold increase | 10 mg/kg KTZ, i.p.; 30 min later, 5 mg/kg MDZ, i.v.; 180 min later, 5 mg/kg KTZ, i.p., to maintain serum KTZ concentrations at ≥2 μg/ml | Sprague-Dawley rats | Kotegawa et al., 2002 | ||
| 3.3-fold increase | 40 mg/kg KTZ, p.o.; 45 min later, 2.5 mg/kg MDZ, p.o. | FVB/N mice | Granvil et al., 2003 | ||
| 6.3-fold increase | 40 mg/kg KTZ, p.o.; 45 min later, 2.5 mg/kg MDZ, p.o. | CYP3A4-humanized FVB/N mice | Granvil et al., 2003 | ||
| 2.8-fold increase | 50 mg/kg KTZ, i.p.; 1 h later, 1 mg/kg MDZ in a cocktail, p.o. | CD-1 mice | This study | ||
| PCN | 10% increase | 10 mg/kg PCN for 3 days, i.g.; 0.3 mg/kg MDZ, i.v. | C57BL/6J mice | Pang et al., 2011 | |
| 25-fold decrease | 40 mg/kg PCN for 3 days, i.p.; 1 mg/kg MDZ in a cocktail, p.o. | CD-1 mice | This study | ||
| PHE | α-NF | 1.8-fold increase | 7 mg/kg α-NF, i.v.; 15 min later, 5 mg/kg PHE, i.v. | Sprague-Dawley rats | Zhuang et al., 2013 |
| 2.3-fold increase | 100 mg/kg α-NF, i.p.; 1 h later 2.8 mg/kg PHE in a cocktail, p.o. | CD-1 mice | This study | ||
| 3-MC | 4.9-fold decrease | 20 mg/kg 3-MC for 2 days, p.o.; 20 mg/kg PHE, i.v. | Wistar rats | Klippert et al., 1983 | |
| 13-fold decrease | 20 mg/kg 3-MC for 2 days, p.o.; 20 mg/kg PHE, i.d. | Wistar rats | Klippert et al., 1983 | ||
| 33-fold decrease | 50 mg/kg 3-MC for 3 days, i.p.; 2.8 mg/kg PHE in a cocktail, p.o. | CD-1 mice | This study |