Summary of the 48 in vivo clinical studies used in prediction
Precipitant | Precipitant Dose | Precipitant Dose Interval | Dose Type | [I] = Csys | fu | Midazolam Dose | Dose Type | Observed DDIa | Referencesb |
---|---|---|---|---|---|---|---|---|---|
Atomoxetine | 60 mg (12 days) | b.i.d. | p.o. | 10.6 | 0.020 | 5 mg | p.o. | 1.2 | Sauer et al., 2004 |
Atorvastatin | 10-40 mg (10 days) | q.d. | p.o. | 0.023 | 0.020 | 0.15 mg/kg | i.v. | 1.41 | Mc Donnell et al., 2003 |
Azithromycin | 500 mg (3 days) | q.d. | p.o. | 0.270 | 0.120 | 15 mg | p.o. | 1.27 | Zimmermann et al., 1996 |
Carbamazepine | 600-800 mg | b.i.d. | p.o. | 34 | 0.26 | 15 mg | p.o. | 0.04 | Backman et al., 1996 |
Chlorzoxazone | 250 mg | q.d. | p.o. | 23.6 | 0.019 | 5 mg | p.o. | 1.68 | Palmer et al., 2001 |
Cimetidine | 400 mg | Single dose | p.o. | 3.27 | 0.790 | 15 mg | p.o. | 1.37 | Fee et al., 1987 |
Cimetidine | 400 mg (1.5 days) | b.i.d. | p.o. | 9.92 | 0.790 | 15 mg | p.o. | 1.35 | Salonen et al., 1986 |
Cimetidine | 800 mg | Single dose | p.o. | 9.92 | 0.790 | 7.5 mg | p.o. | 1.50 | Martinez et al., 1999 |
Cimetidine | 200 mg + 400 mg (1.5 days) | q.i.d. | p.o. | 3.27 | 0.790 | 15 mg | p.o. | 2.02 | Elliott et al., 1984 |
Clarithromycin | 250 mg (5 days) | b.i.d. | p.o. | 2.40 | 0.300 | 15 mg | p.o. | 3.57 | Yeates et al., 1996 |
Clarithromycin | 500 mg (7 days) | b.i.d. | p.o. | 3.00 | 0.300 | 8 mg | p.o. | 8.40 | Gurley et al., 2006 |
Conivaptan | 20 mg (5 days) | b.i.d. | p.o. | 0.159 | 0.015 | 2 mg | p.o. | 3.49 | NDA 021697 |
Conivaptan | 40 mg (5 days) | b.i.d. | p.o. | 0.433 | 0.016 | 2 mg | p.o. | 5.76 | NDA 021697 |
Diltiazem | 60 mg (2 days) | t.i.d. | p.o. | 0.140 | 0.220 | 15 mg | p.o. | 3.75 | Backman et al., 1994b |
Erythromycin | 500 mg (5 days) | t.i.d. | p.o. | 0.950 | 0.160 | 15 mg | p.o. | 3.81 | Zimmermann et al. 1996 |
Erythromycin | 500 mg (7 days) | t.i.d. | p.o. | 0.950 | 0.160 | 15 mg | p.o. | 4.42 | Olkkola et al., 1993 |
Fluconazole | 400 mg | Single dose | p.o. | 29.4 | 0.890 | 1 mg | i.v. | 1.94 | Kharasch et al., 2005 |
Fluconazole | 400 mg, 200 mg (5 days) | q.d. | p.o. | 29.4 | 0.890 | 7.5 mg | p.o. | 3.60 | Olkkola et al., 1996 |
Flumazenil | 1.75 mg | Single dose | i.v. | 0.001 | 0.600 | 0.35 mg | i.v. | 0.97 | Rogers et al., 2002 |
Fluoxetine | 60 mg (5 days), 20 mg (7 days) | q.d. | p.o. | 0.353 | 0.050 | 10 mg | p.o. | 0.87 | Lam et al., 2003 |
Fluvoxamine | 50-100 mg (12 days) | b.i.d. | p.o. | 0.342 | 0.230 | 10 mg | p.o. | 1.66 | Lam et al., 2003 |
Gatifloxacin | 400 mg (5 days) | q.d. | p.o. | 3.82 | 0.800 | 1 mg | i.v. | 1.80 | Grasela et al., 2000 |
Itraconazole | 200 mg (4 days) | q.d. | p.o. | 0.270 | 0.002 | 7.5 mg | p.o. | 10.8 | Olkkola et al., 1994 |
Itraconazole | 100 mg (4 days) | q.d. | p.o. | 0.128 | 0.002 | 7.5 mg | p.o. | 5.74 | Ahonen et al., 1995 |
Itraconazole | 200 mg (6 days) | q.d. | p.o. | 0.270 | 0.002 | 7.5 mg | p.o. | 6.64 | Olkkola et al., 1996 |
Itraconazole | 200 mg (4 days) | q.d. | p.o. | 0.270 | 0.002 | 7.5 mg | p.o. | 6.16 | Backman et al., 1998 |
Ketoconazole | 200 mg (1.5 days) | b.i.d. | p.o. | 5.42 | 0.010 | 2 mg | i.v. | 5.0 | Tsunoda et al., 1999 |
Ketoconazole | 200 mg (1.5 days) | b.i.d. | p.o. | 5.42 | 0.010 | 6 mg | p.o. | 13.6 | Tsunoda et al., 1999 |
Ketoconazole | 200 mg (5 days) | Single dose | p.o. | 1.87 | 0.010 | 2 mg | p.o. | 5.2 | McCrea et al., 1999 |
Ketoconazole | 200 mg (5 days) | Single dose | p.o. | 1.87 | 0.010 | 2 mg | p.o. | 6.5 | McCrea et al., 1999 |
Ketoconazole | 200 mg (12 days) | q.d. | p.o. | 1.88 | 0.010 | 10 mg | p.o. | 8.7 | Lam et al., 2003 |
Ketoconazole | 200 mg (4 days) | b.i.d. | p.o. | 4.76 | 0.010 | 75 ug | p.o. | 6.5 | Eap et al., 2004 |
Ketoconazole | 400 mg (10 days) | q.d. | p.o. | 2.82 | 0.010 | 5.5 mg | p.o. | 9.5 | Chung et al., 2006 |
Ketoconazole | 400 mg (4 days) | q.d. | p.o. | 2.82 | 0.010 | 7.5 mg | p.o. | 15.9 | Olkkola et al., 1994 |
Mibefradil | 100 mg | Single dose | p.o. | 1.24 | 0.005 | 2 mg | p.o. | 8.9 | Veronese et al., 2003 |
Nefazodone | 100-200 mg (12 days) | b.i.d. | p.o. | 1.73 | 0.009 | 10 mg | p.o. | 5.4 | Lam et al., 2003 |
Nitrendipine | 20 mg (4 days) | q.d. | p.o. | 0.041 | 0.016 | 20 mg | i.v. | 0.9 | Handel et al., 1988 |
Parecoxib | 40 mg | Single dose | i.v. | 2.53 | 0.020 | 0.07 mg/kg | i.v. | 1.1 | Ibrahim et al., 2002 |
Ranitidine | 150 mg (1.5 days) | b.i.d. | p.o. | 1.47 | 0.850 | 15 mg | p.o. | 1.2 | Fee et al., 1987 |
Ranitidine | 300 mg | Single dose | p.o. | 1.47 | 0.850 | 7.5 mg | p.o. | 1.3 | Martinez et al., 1999 |
Ranitidine | 150 mg (1.5 days) | b.i.d. | p.o. | 1.15 | 0.850 | 15 mg | p.o. | 1.7 | Elliott et al., 1984 |
Rifampin | 600 mg (5 days) | q.d. | p.o. | 12.50 | 0.250 | 8 mg | p.o. | 0.1 | Backman et al., 1996 |
Roxithromycin | 300 mg (6 days) | q.d. | p.o. | 5.13 | 0.140 | 15 mg | p.o. | 1.5 | Backman et al., 1994a |
Saquinavir | 1200 mg (5 days) | t.i.d. | p.o. | 0.430 | 0.020 | 7.5 mg | p.o. | 5.2 | Palkama et al., 1999 |
Saquinavir | 1200 mg (5 days) | t.i.d. | p.o. | 0.430 | 0.020 | 0.05 mg/kg | i.v. | 2.5 | Palkama et al., 1999 |
Simvastatin | 80 mg (7 days) | q.d. | p.o. | 0.026 | 0.060 | 2 mg | p.o. | 1.1 | Prueksaritanont et al., 2000 |
Terbinafine | 250 mg (4 days) | q.d. | p.o. | 2.13 | 0.010 | 7.5 mg | p.o. | 0.76 | Ahonen et al., 1995 |
Troleandomycin | 500 mg (2 days) | b.i.d. | p.o. | 1.76 | 0.038 | 10 mg | p.o. | 14.8 | Kharasch et al., 2004 |
Valdecoxib | 40 mg | b.i.d. | p.o. | 2.90 | 0.020 | 10 mg | p.o. | 1.1 | Unpublished data |
Verapamil | 80 mg (2 days) | t.i.d. | p.o. | 0.480 | 0.100 | 15 mg | p.o. | 2.9 | Backman et al., 1994b |