TABLE 3

Repaglinide drug-drug interactions in vivo with details on main P450 enzymes involved, administered repaglinide dose, number of subjects, change in repaglinide AUC, and change in metabolite AUC ratios

Inhibitor	Main P450 Involved	Repaglinide Dose	No. Subjects	Fold Change in Repaglinide AUC	Fold Change in M2/M1 AUC Ratio	Fold Change in M2/M4 AUC Ratio	Reference
		mg
Gemfibrozil^{^a}	CYP2C8	0.25	12	8.1	Not reported	Not reported	Niemi et al., 2003
Itraconazole	CYP3A4	0.25	12	1.4	Not reported	Not reported	Niemi et al., 2003
Gemfibrozil^{^a} + Itraconazole	CYP2C8 + CYP3A4	0.25	12	19	Not reported	Not reported	Niemi et al., 2003
Gemfibrozil^{^a}	CYP2C8	0.25	10	5.0–7.0^{^b}	0.39–0.57^{^b}	2.3–9.7^{^b}	Tornio et al., 2008
Atorvastatin^{^a}	CYP3A4	0.25	24	N.S.–1.2^{^c}	1.05–1.3^{^c}	0.87–1.1^{^c}	Kalliokoski et al., 2008a
Gemfibrozil^{^a}	CYP2C8	0.25	24	7.3–8.2^{^c}	0.38–0.52^{^c}	6.4–10.4^{^c}	Kalliokoski et al., 2008a
Gemfibrozil^{^a}	CYP2C8	0.25	9	1.0–7.6^{^b}	0.42–1.2^{^b}	0.94–18^{^b}	Backman et al., 2009
Telithromycin	CYP3A4	0.25	12	1.8	3.9	0.80	Kajosaari et al., 2006b
Montelukast	CYP2C8	0.25	12	N.S.	1.1	0.98	Kajosaari et al., 2006b
Telithromycin + montelukast	CYP3A4 + CYP2C8	0.25	12	1.9^{^d}	4.3	0.82	Kajosaari et al., 2006b
Pioglitazone	CYP2C8 + CYP3A4	0.25	12	N.S.	Not reported	Not reported	Kajosaari et al., 2006a
Clarithromycin	CYP3A4	0.25	9	1.4	Not reported	Not reported	Niemi et al., 2001
Trimethoprim	CYP2C8	0.25	9	1.6	Not reported	Not reported	Niemi et al., 2004
Cyclosporine^{^a}	CYP3A4	0.25	12	2.4	Not reported	Not reported	Kajosaari et al., 2005
Ketoconazole	CYP3A4	2	8	N.S.	Not reported	Not reported	Hatorp et al., 2003
Bezafibrate	CYP2C8	0.25	12	N.S.	Not reported	Not reported	Kajosaari et al., 2004
Fenofibrate	CYP2C8	0.25	12	N.S.	Not reported	Not reported	Kajosaari et al., 2004

N.S., not significant.
↵a OATP1B1 also involved.
↵b Depending on time interval between repaglinide and gemfibrozil doses.
↵c Depending on SLCO1B1 genotype.
↵d Not significantly different from telithromycin phase.