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

Aliment Pharmacol Ther. 2021 Mar;53(5):608-615. doi: 10.1111/apt.16239. Epub 2020 Dec 28.

Abstract

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 13 C-aminopyrine breath test (13 C-ABT) is a non-invasive tool to study CYP450-dependent liver function.

Aims: 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 20 mg/day, esomeprazole 20 mg/day, lansoprazole 15 mg/day, pantoprazole 40 mg/day or rabeprazole 20 mg/day. 13 C-ABT was performed at baseline and on the 15th day of PPI therapy.

Results: At baseline, mean values of max 13 C% dose/h and 13 C% cum dose at 120 minutes did not differ significantly among groups. On the 15th day of therapy, max 13 C% dose/h and 13 C% 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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Aminopyrine
  • Anti-Ulcer Agents*
  • Breath Tests
  • Cytochrome P-450 Enzyme System
  • Esomeprazole
  • Humans
  • Lansoprazole
  • Liver Cirrhosis / drug therapy
  • Proton Pump Inhibitors*
  • Rabeprazole

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Ulcer Agents
  • Proton Pump Inhibitors
  • Aminopyrine
  • Lansoprazole
  • Rabeprazole
  • Cytochrome P-450 Enzyme System
  • Esomeprazole