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

Abstract

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 13 C-aminopyrine breath test (13 C-ABT) is a non-invasive tool to study CYP450-dependent liver function. To assess 13 C-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 20mg/day, esomeprazole 20mg/day, lansoprazole 15mg/day, pantoprazole 40mg/day or rabeprazole 20mg/day. 13 C-ABT was performed at baseline and on the 15th day of PPI therapy. At baseline, mean values of max 13 C% dose/h and 13 C% cum dose at 120minutes did not differ significantly among groups. On the 15th day of therapy, max 13 C% dose/h and 13 C% cum dose at 120minutes 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). 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.