Summary of victim-gemfibrozil DDI predictions using mechanistic static models
| Static Model | Victim Drug | Gemfibrozil Dose | fmCYP2C8a | FRenal | Fsec | Observed AUCR | Predicted (Gemfibrozil Only) | Predicted (Gemfibrozil and Gem-Glu) | References |
|---|---|---|---|---|---|---|---|---|---|
| NE | (S)-warfarin | 600 mg (8 d) | 0 | 0.9 | 1.0 | 1.0 | (Kaminsky and Zhang, 1997; Lilja et al., 2005) | ||
| NE | Lovastatin | 600 mg (3 d) | 0 | 0.9 | 1.0 | 1.0 | (Wang et al., 1991; Chen et al., 2012) | ||
| NE | Imatinib | 600 mg (6 d) | 0.25 | 0.05 | 0.46 | 0.9 | 1.1 | 1.3 | (Nebot et al., 2010; Filppula et al., 2013) |
| NE | (R)-warfarin | 600 mg (8 d) | 0 | 0.9 | 1.0 | 1.0 | (Kaminsky and Zhang, 1997; Lilja et al., 2005) | ||
| NE | Brivaracetam | 600 mg (7 d) | 0 | 0.9 | 1.0 | 1.0 | (Nicolas et al., 2012) | ||
| NE | Lovastatin | 600 mg (3 d) | 0 | 1.0 | 1.0 | 1.0 | (Wang et al., 1991; Kyrklund et al., 2001) | ||
| NE | Zopiclone | 600 mg (3 d) | 0.3 | 0.03 | 0 | 1.0 | 1.1 | 1.4 | (Becquemont et al., 1999; Tornio et al., 2006) |
| NE | Zafirlukast | 600 mg (5 d) | 0 | 1.0 | 1.0 | 1.0 | (Dekhuijzen and Koopmans, 2002; Karonen et al., 2011) | ||
| NE | (S)-ibuprofen | 600 mg (3 d) | 0.23 | 1.1 | 1.1 | 1.3 | (Tornio et al., 2007; Chang et al., 2008) | ||
| NE | Alogliptin | 600 mg (7 d) | 0 | 0.71 | 0.38 | 1.1 | 1.1 | 1.2 | |
| NE | Glimepiride | 600 mg (2.5 d) | 0.2 | 1.2 | 1.1 | 1.2 | (Niemi et al., 2001) | ||
| NE | (R)-ibuprofen | 600 mg (3 d) | 0.25 | 1.3 | 1.1 | 1.3 | (Tornio et al., 2007; Chang et al., 2008) | ||
| NE | Simvastatin | 600 mg (3 d) | 0 | 1.4 | 1.0 | 1.0 | (Backman et al., 2000; Prueksaritanont et al., 2003) | ||
| ENE | Atorvastatin acid | 600 mg (7 d) | 0 | 1.4 | 1.8 | 2.7 | (Whitfield et al., 2011) | ||
| NE | Ezetimibe | 600 mg (7 d) | 0 | 1.5 | 1.0 | 1.0 | (Ghosal et al., 2004; Reyderman et al., 2004; Kosoglou et al., 2005) | ||
| NE | Sitagliptin | 600 mg (3 d) | 0 | 0.7 | 0.73 | 1.5 | 1.2 | 1.4 | (Vincent et al., 2007; Arun et al., 2012) |
| ENE | Pitavastatin | 600 mg (7 d) | 0 | 1.5 | 1.8 | 2.8 | |||
| NE | Empagliflozin | 600 mg (5 d) | 0 | 0.16 | 0.26 | 1.6 | 1.0 | 1.0 | (Macha et al., 2014) |
| ENE | Repaglinide | 30 mg | 0.71 | 1.8 | 1.0 | 1.9 | (Honkalammi et al., 2011a) | ||
| ENE | Rosuvastatin | 600 mg (7 d) | 0 | 1.9 | 1.8 | 2.7 | (Schneck et al., 2004) | ||
| ENE | Pravastatin | 600 mg (3 d) | 0 | 2.0 | 1.7 | 2.2 | (Kyrklund et al., 2003) | ||
| NE | Loperamide | 600 mg (5 d) | 0.38 | 2.2 | 1.1 | 1.6 | (Kim et al., 2004; Niemi et al., 2006) | ||
| NE | Rosiglitazone | 600 mg (4 d) | 0.65 | 2.3 | 1.2 | 2.8 | (Baldwin et al., 1999; Niemi et al., 2003a) | ||
| NE | Pioglitazone | 600 mg (4 d) | 0.68 | 3.1 | 1.2 | 3.1 | (Jaakkola et al., 2006; Aquilante et al., 2013) | ||
| NE | Pioglitazone | 600 mg (4 d) | 0.68 | 3.2 | 1.2 | 3.1 | (Jaakkola et al., 2005, 2006) | ||
| NE | Pioglitazone | 600 mg (1 wk) | 0.68 | 3.4 | 1.2 | 3.1 | (Deng et al., 2005; Jaakkola et al., 2006) | ||
| ENE | Repaglinide | 30 mg (5 d) | 0.71 | 3.4 | 1.0 | 1.9 | (Honkalammi et al., 2012) | ||
| NE | Pioglitazone | 600 mg (4 d) | 0.68 | 3.8 | 1.2 | 3.1 | (Jaakkola et al., 2006; Aquilante et al., 2013) | ||
| NE (+Itra) | Pioglitazone | 600 mg + 100 mg Itra (4 d) | 0.68 (0.1) | 3.9 | 1.3 | 4.5 | (Jaakkola et al., 2005) | ||
| NE (+Itra) | Montelukast | 600 mg + 100 mg Itra (5 d) | 0.81 (0.0) | 4.0 | 1.2 | 5.2 | (Karonen et al., 2012) | ||
| NE | Enzalutamide | 600 mg (21 d) | 0.75 | 4.3 | 1.2 | 4.0 | |||
| NE | Montelukast | 600 mg (5 d) | 0.81 | 4.3 | 1.2 | 5.2 | (Karonen et al., 2012) | ||
| ENE | Cerivastatin | 600 mg (3 d) | 0.6 | 4.4 | 1.9 | 4.3 | (Backman et al., 2002) | ||
| NE | Montelukast | 600 mg (3 d) | 0.81 | 4.5 | 1.2 | 5.2 | (Karonen et al., 2010) | ||
| ENE | Repaglinide | 100 mg | 0.71 | 4.5 | 1.1 | 2.3 | (Kajosaari et al., 2005a; Honkalammi et al., 2011a) | ||
| NE | Pioglitazone | 600 mg (4 d) | 0.68 | 4.7 | 1.2 | 3.1 | (Jaakkola et al., 2006; Aquilante et al., 2013) | ||
| ENE | Repaglinide | 600 mg | 0.71 | 5.0 | 1.9 | 4.8 | (Kajosaari et al., 2005a; Honkalammi et al., 2011b) | ||
| ENE | Repaglinide | 100 mg (5 d) | 0.71 | 5.6 | 1.1 | 2.3 | (Kajosaari et al., 2005a; Honkalammi et al., 2012) | ||
| ENE | Repaglinide | 600 mg | 0.71 | 6.4 | 1.9 | 4.8 | (Kajosaari et al., 2005a; Honkalammi et al., 2011b) | ||
| ENE | Repaglinide | 300 mg | 0.71 | 6.7 | 1.4 | 3.4 | (Kajosaari et al., 2005a; Honkalammi et al., 2011a) | ||
| ENE | Repaglinide | 600 mg (2.5 d) | 0.71 | 7.0 | 1.9 | 4.8 | (Kajosaari et al., 2005a; Tornio et al., 2008) | ||
| ENE | Repaglinide | 600 mg (5 d) | 0.71 | 7.0 | 1.9 | 4.8 | (Kajosaari et al., 2005a; Honkalammi et al., 2012) | ||
| ENE | Repaglinide | 600 mg (3 d) | 0.71 | 7.6 | 1.9 | 4.8 | (Kajosaari et al., 2005a; Backman et al., 2009) | ||
| ENE | Repaglinide | 600 mg (3 d) | 0.71 | 7.7 | 1.9 | 4.8 | (Kajosaari et al., 2005a; Kalliokoski et al., 2008) | ||
| ENE | Repaglinide | 600 mg (3 d) | 0.71 | 8.1 | 1.9 | 4.8 | (Niemi et al., 2003b; Kajosaari et al., 2005a) | ||
| ENE | Repaglinide | 900 mg | 0.71 | 8.3 | 2.3 | 6.0 | (Kajosaari et al., 2005a; Honkalammi et al., 2011a) | ||
| NE (+Itra) | Loperamide | 600 mg + 100 mg Itra (5 d) | 0.38 (0.53) | 12.6 | 3.6 | 13.4 | (Kim et al., 2004; Niemi et al., 2006) | ||
| ENE (+Itra) | Repaglinide | 600 mg + 100 mg Itra (3 d) | 0.71 (0.24) | 19.3 | 3.5 | 26.5 | (Niemi et al., 2003b; Kajosaari et al., 2005a) |
ENE, extended net-effect model; Itra, itraconazole; NE, net effect model.
↵a Value in parentheses indicates fmCYP3A4.