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

Abstract

SummaryBackgroundChronic 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.AimsTo assess 13C‐ABT modifications with different PPIs in patients with cirrhosisMethodsSixty 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.ResultsAt 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).ConclusionsIn 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.

Proton pump inhibitors affect sperm parameters by regulating aquaporins

“…In patients with liver cirrhosis, omeprazole, esomeprazole and lansoprazole have inhibitory effects on liver enzyme microsomal activity [ 21 ]. In the presence of omeprazole, the N-demethylase activity of CYP3A4 measured by formaldehyde generation method to erythromycin obvious decreased [ 22 ].…”