“…Although in vitro studies are not fully consistent with the major in vivo role of CYP2C8 in the total metabolism of repaglinide (Gan et al, 2010;Säll et al, 2012;Varma et al, 2013Varma et al, , 2015, repaglinide seems to be very sensitive to inhibitors of CYP2C8 activity, such as gemfibrozil, trimethoprim, and clopidogrel (Niemi et al, 2003b(Niemi et al, , 2004bTornio et al, 2014). On the basis of detailed mechanistic drug-drug interaction studies with the strong CYP2C8 inactivator gemfibrozil, it has been estimated that the contribution of CYP2C8 to repaglinide (0.25 mg) metabolism is about 85%, indicating that the AUC of repaglinide can be increased up to an average of sevenfold by strong CYP2C8 inhibition (Honkalammi et al, 2012).…”