The Efficacy of Ranitidine and Once-Daily or Twice-Daily Orally Administered Omeprazole on Intragastric pH in Cats

Summarised by Dr Liesel van der Merwe BSVC MMed(Vet)Med Small Animals

Sutalo, S, Ruetten M et al, 2015. The Effect of Orally Administered Ranitidine and Once-Daily or Twice- Daily Orally Administered Omeprazole on Intragastric pH in Cats. Journal of Veterinary Internal Medicine (29): 840 – 846

Why they did it?

The clinical efficacy of gastric acid anti-secretory drugs is largely unknown. Acid suppressant medications are however commonly used in cats clinical practice at dosages extrapolated from studies in dogs. The goals of the study were to determine normal gastric acid profiles in healthy cats, to investigate the effect of omeprazole and ranitidine on intragastric pH in a placebo controlled study and finally to compare once daily and twice daily dosage regimens of omeprazole in cats.

What they did?

The study was a randomised crossover design using a placebo on 8 healthy European shorthair olony cats . All cats underwent a gastroduodenal endoscopy and biopsy procedure prior to inclusion. Treatments were administered per os for 7 consecutive days. Washout time was a median of 12 days (7 – 24 days). All drugs were administered in gelatin capsules (which were evaluated and shown to dissolve within 5 minutes in a range of pHs’) which were fed with a small amount of food (shown not to affect absorption). The treatments were-: placebo (empty gelatin capsule) bid, ranitidine at 1.5 -2.3 (median 1.9)mg/kg bid, omeprazole at 1.1 -1.3mg/kg (median 1.2)mg/kg oid and omeprazole at 1.1 -1.3mg/kg (median 1.2)mg/kg bid.

(NOTE: one enteric coated granule from the capsules contains 1.1mg of omeprazole – so cats were given 1 granule / kg body weight to approximate 1 mg/kg dose. Used in paediatric patients like this as well. The journal scan of the article by Parkinson et al in this issue shows that subdividing the enteric coated tablets is also effective)

Gastric pH was measured using a capsule (Bravo™ system) fixed to the gastric mucosa. The capsule was placed endoscopically on day 4 of treatment. The pH was telemetrically monitored at 6 sec sampling intervals for 4 days.

Three factors were compared: the percentage of time intra-gastric pH was ≥ 3 and also ≥ 4 from days 4 -7 of treatment, in which category of pH ( 0-1, 1-2, 2-3, 3-4, 4-5, 5-6, 6-7, 7-8 ) the pH was for the most time from days 4-7 of treatment and finally the adverse effects to the cat with regards to defaecation frequency and faecal scores as soft faeces occur in humans and dogs with per os administered omeprazole.

Treatment

Placebo bid

Ranitidine bid

Omeprazole oid

Omeprazole bid

% time intra-gastric pH ≥ 3

9.4 ± 8%

16.5 ± 9%

24.4 ±22.8%

67.0 ± 24.0% *

% time intra-gastric pH ≥ 4

7.0 ± 6.6%

9.6 ± 5.9%

16.8 ± 19.3%

54.6 ± 26.4%**

*p=0.011 ** p =0.044

What they found?

Gross gastroduodenal evaluation was normal in all eight cats, but on histopathology all the cats had severe colonisation of the mucousal surface with Helicobacter spp. Small clusters of neutrophils were observed in the lamina propria of all the cats. The final histologic diagnosis was gastric colonisation by Helicobacter spp. The prevalence of colonisation by Helicobacter spp without concurrent gastritis is high in cats, so the findings were considered typical of what is seen in cats

A total of 745580 pH points were measured (94.7%). The table reflects the findings at intra-gastric pH ≥ 3 and ≥4. Intra-gastric pH varied widely across all pH categories but twice daily omeprazole treatment groups spent the most time in intra-gastric pH categories 3-4 to 6-7. There was no difference between the groups on faecal scores.

There was a large degree of individual variation in response to omeprazole , and much less to ranitidine. One cat had almost 100% intra-gastric acid suppression on bid omeprazole whereas another on had only about 3%. This occurs in humans as well and non-responders are thought to have a defect in the p-450 cytochome metabolism. (author – so test case numbers could ideally have been higher)

Take home message

A significant increase in the gastric pH on days 4-7 was only seen in the cats treated with bid omeprazole. The effects of ranitidine and the placebo on intra-gastric pH did not differ in this study. Twice a day administration of omeprazole at 1mg/kg appears to be the treatment of choice for cats with acid related gastrointestinal disease.

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