Effects of pirenzepine on vonoprazan-induced gastric acid inhibition and hypergastrinemia

Backgrounds: Compared to proton pump inhibitors, vonoprazan exerts a greater inhibitory effect on gastric acid secretion and is useful for treating acid-related diseases, such as gastro-esophageal reflux disease. However, there is a problem that vonoprazan causes hypergastrinemia, which confers a risk of carcinoid tumor. A previous report demonstrated that pirenzepine, an M1 muscarinic receptor antagonist, enhances the acid inhibitory effects while suppressing hypergastrinemia induced by omeprazole. Here, we examined whether pirenzepine enhances the gastric acid inhibitory effects of vonoprazan without further increasing serum gastrin levels.Methods: Eleven healthy volunteers were subjected to 24-hour intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: pirenzepine 75mg alone, vonoprazan 10mg alone, and vonoprazan 10mg plus pirenzepine 75mg administered in a randomized crossover fashion.Results: Median pH 4 holding time ratios (range) achieved with pirenzepine 75mg, vonoprazan 10mg and vonoprazan 10mg plus pirenzepine 75mg were 6.9% (2.4–32.8%), 88.4% (54.6–100%), and 84.2% (40.3–100%), respectively. Respective serum gastrin levels were 79 (75–210) pg/ml, 310 (110–870) pg/ml, and 170 (140–930) pg/ml. In cases with hypergastrinemia (gastrin≥200pg/ml) induced by vonoprazan 10mg alone, concomitant treatment with pirenzepine significantly reduced serum gastrin levels from 370pg/ml to 180pg/ml (P=0.028).Conclusion: Although pirenzepine does not enhance acid inhibition, it does improve hypergastrinemia induced by vonoprazan to some extent.