Impact of proton pump inhibitors on cytochrome P450 activity assessed by 13C-aminopyrine breath test in patients with cirrhosis

Background: Chronic use of proton pump inhibitors (PPIs) in patients with impaired liver function may worsen cytochrome P450 (CYP450) activity, predisposing them to clinically relevant drug–drug interactions. The 13C-aminopyrine breath test (13C-ABT) is a non-invasive tool to study CYP450-dependent liver function. Aims: To assess 13C-ABT modifications with different PPIs in patients with cirrhosis. Methods: Sixty consecutive patients with HCV-related cirrhosis and indication to start PPI therapy were randomised to receive omeprazole 20 mg/day, esomeprazole 20 mg/day, lansoprazole 15 mg/day, pantoprazole 40 mg/day or rabeprazole 20 mg/day. 13C-ABT was performed at baseline and on the 15th day of PPI therapy. Results: At baseline, mean values of max 13C% dose/h and 13C% cum dose at 120 minutes did not differ significantly among groups. On the 15th day of therapy, max 13C% dose/h and 13C% cum dose at 120 minutes did not significantly differ with respect to baseline for pantoprazole (P = 0.184 and P = 0.309, respectively) or rabeprazole (P = 0.536 and P = 0.286, respectively), but were significantly decreased on omeprazole (P = 0.013 and P = 0.015, respectively), esomeprazole (P = 0.009 and P = 0.001, respectively), and lansoprazole (P = 0.033 and P = 0.035, respectively). Conclusions: In patients with cirrhosis, omeprazole, esomeprazole and lansoprazole inhibit microsomal activity while pantoprazole and rabeprazole do not have a significant impact. Should our data be confirmed in larger cohort studies, pantoprazole and rabeprazole could be safely recommended for patients with cirrhosis.