Effect of repeated doses of netazepide, a gastrin receptor antagonist, omeprazole and placebo on 24 h gastric acidity and gastrin in healthy subjects
Article first published online: 21 OCT 2013
© 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 76, Issue 5, pages 680–688, November 2013
How to Cite
Boyce, M. and Warrington, S. (2013), Effect of repeated doses of netazepide, a gastrin receptor antagonist, omeprazole and placebo on 24 h gastric acidity and gastrin in healthy subjects. British Journal of Clinical Pharmacology, 76: 680–688. doi: 10.1111/bcp.12095
- Issue published online: 21 OCT 2013
- Article first published online: 21 OCT 2013
- Accepted manuscript online: 21 FEB 2013 08:29AM EST
- Manuscript Accepted: 14 JAN 2013
- Manuscript Received: 3 OCT 2012
- gastric pH;
- gastrin receptor antagonist;
- netazepide (YF476);
- plasma gastrin
To administer repeated oral doses of netazepide to healthy subjects for the first time, to assess safety, tolerability, pharmacokinetics and effect on 24 h gastric pH and plasma gastrin.
We did two randomized, double-blind, parallel group studies. The first compared netazepide 25 and 100 mg 12 hourly, omeprazole 20 mg once daily and placebo for 7 days. On day 7 only, we measured pH and assayed plasma gastrin. The second study compared netazepide 5, 10 and 25 mg and placebo once daily for 14 days. We measured pH on days 1, 7 and 14 and assayed plasma gastrin on days 1 and 14. We compared treatments by time gastric pH ≥ 4 during 0–4, 4–9, 9–13 and 13–24 h after the morning dose, and by plasma gastrin. P < 0.05 was significant.
Netazepide was well tolerated. On day 7 of the first study, netazepide increased pH significantly only during 9–13 h after the 100 mg dose, whereas omeprazole raised pH significantly during all periods. Both netazepide and omeprazole increased plasma gastrin significantly. Netazepide had linear pharmacokinetics. In the second study, netazepide caused dose-dependent, sustained increases in pH on day 1, but as in the first study, netazepide had little effect on pH on days 7 and 14. Again, netazepide increased plasma gastrin significantly.
Although repeated doses of netazepide led to tolerance to its effect on pH, the accompanying increase in plasma gastrin is consistent with continued inhibition of acid secretion, via gastrin receptor antagonism and gene up-regulation.