Effects of selective serotonin reuptake inhibitors on the pharmacokinetics of proton pump inhibitors

By now, the differential effects of several selective serotonin reuptake inhibitors (SSRIs) on the cytochrome P450 (CYP) enzymes are well defined and that the drug-drug interactions (DDIs) are a major issue in the management of depression. In many cases of DDIs in relation to SSRIs, SSRIs plays as a potent CYP inhibitor. Fluvoxamine has inhibited various CYPs-mediated pathways (especially CYP1A2, 2C9/19 and 3A4) and P-gp-mediated transport of substrate drugs. While, the metabolism of proton pump inhibitors (PPIs) is related to cytochrome P450 (CYP) 3A4 and polymorphic CYP2C19, and PPIs such as omeprazole and lansoprazole have also shown to be substrates of P-glycoprotein (P-gp) in in vitro study. Therefore, this review summarized the DDIs of Fluvoxamine-PPIs in Japanese healthy volunteers and the findings indicated that the DDIs of fluvoxamine-PPIs may be associated with the sum of polymorphic CYP2C19, CYP3A4 and P-gp.