Effects of single intravenously administered doses of omeprazole and ranitidine on intragastric pH and plasma gastrin concentration in nonfed ponies

Simon J. Baker From the Department of Large Animal Medicine and Surgery, Royal Veterinary College, University of London, North Mymms, Hatfield, Hertfordshire, England AL9 7TA.

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 VetMB, PhD
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E. Lawrence Gerring From the Department of Large Animal Medicine and Surgery, Royal Veterinary College, University of London, North Mymms, Hatfield, Hertfordshire, England AL9 7TA.

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 BVSc, PhD

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Summary

We investigated the effects of a range of iv administered doses of omeprazole (0.125 to 2.0 mg/kg of body weight) on gastric pH (monitored by indwelling electrode) and plasma gastrin concentration, compared with those of iv administered ranitidine (1.0 mg/kg) in 4 Welsh mountain-type ponies. Pharmacokinetic variables of iv administered omeprazole also were examined. Episodes of high gastric pH in the basal state obscured the effect of acid suppression on intragastric pH; however, omeprazole induced dose-dependent increase in mean gastric pH (P < 0.01) during the 11 hours after its administration. In the presence of acid-suppressant treatment, plasma gastrin concentration correlated significantly with gastrie pH (Spearman's rank correlation coefficient, ρ = 0.445, P < 0.01), whereas basal pH and plasma gastrin concentration were not correlated. The effect was not great, and a dose-dependency was not found. Intravenously administered omeprazole was subject to two-compartment pharmacokinetics, and there was evidence for saturable steps in the redistribution and elimination phases. Dosage of 0.25 mg/kg induced approximately half-maximal inhibition of basal gastric pH in these ponies and was associated with area under the concentration vs time curve of 0.7 μmol·h/L, which corresponds reasonably with results of other species. Omeprazole may represent a useful alternative acid-suppressant agent in horses, but further work is required to relate the dose-dependent effects found in this study to well-defined targets of acid suppression in clinical cases.

Summary

We investigated the effects of a range of iv administered doses of omeprazole (0.125 to 2.0 mg/kg of body weight) on gastric pH (monitored by indwelling electrode) and plasma gastrin concentration, compared with those of iv administered ranitidine (1.0 mg/kg) in 4 Welsh mountain-type ponies. Pharmacokinetic variables of iv administered omeprazole also were examined. Episodes of high gastric pH in the basal state obscured the effect of acid suppression on intragastric pH; however, omeprazole induced dose-dependent increase in mean gastric pH (P < 0.01) during the 11 hours after its administration. In the presence of acid-suppressant treatment, plasma gastrin concentration correlated significantly with gastrie pH (Spearman's rank correlation coefficient, ρ = 0.445, P < 0.01), whereas basal pH and plasma gastrin concentration were not correlated. The effect was not great, and a dose-dependency was not found. Intravenously administered omeprazole was subject to two-compartment pharmacokinetics, and there was evidence for saturable steps in the redistribution and elimination phases. Dosage of 0.25 mg/kg induced approximately half-maximal inhibition of basal gastric pH in these ponies and was associated with area under the concentration vs time curve of 0.7 μmol·h/L, which corresponds reasonably with results of other species. Omeprazole may represent a useful alternative acid-suppressant agent in horses, but further work is required to relate the dose-dependent effects found in this study to well-defined targets of acid suppression in clinical cases.

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