Consistent inhibition of acid output with repeated dosing of AZD0865 in rats

Background/Aim AZD0865, a potassium‐competitive acid blocker (P‐CAB), provides dose‐dependent inhibition of acid secretion. In rats, after a single 1 μmol/kg oral dose, complete inhibition of acid secretion was maintained 2–4.5 h post‐dose. We assessed the antisecretory effects of repeated, lower doses of AZD0865. Methods Three groups of 8 chronic fistula rats received single, oral doses (0, 0.25, 0.5 μmol/kg, respectively) of AZD0865 for 16 days. Pentagastrin+carbachol‐stimulated gastric acid secretion was assessed in the 2.5–4.5 h period after dose on the 1st, 4th, 8th and 14th day. Vehicle‐controlled secretory responses were also assessed in all groups, both before the dosing period, and on the 1st (i.e. 24h) and 5th day after the last dose. Results The average inhibition of acid output in the 0.25 μmol/kg group was 58%, 73%, 64% and 59% on the 1st, 4th, 8th and 14th day of dosing, respectively. In the 0.5 μmol/kg group, corresponding results were 98%, 100%, 100% and 99%. There was no statistically significant difference in inhibition of acid output between 1st and 4th, 8th or 14th dose in either groups. Control level secretory responses were recorded 24h and 5 days after the last dose. Conclusions The 2.5–4.5 h antisecretory effect of AZD0865 is consistent after one and several doses in the rat. Even at a submaximal dose (0.25 μmol/kg), the peak level of inhibition over the 24‐h dosing interval displayed after the first dose is maintained with subsequent doses. Clinical Pharmacology & Therapeutics (2005) 77 , P55–P55; doi: 10.1016/j.clpt.2004.12.101