Effects of misoprostol and omeprazole on basal gastric pH and free acid content in horses

Background: Misoprostol is an E prostanoid (EP) 2, 3 and 4 receptor agonist that is anecdotally used to treat and prevent NSAID-induced GI injury in horses. Misoprostol elicits anti-inflammatory effects in vivo in men and rodents, and inhibits TNFa production in equine leucocytes in vitro. Objective: Define the pharmacokinetic parameters of oral misoprostol in horses, and determine the inhibitory effect of oral misoprostol administration on equine leucocyte TNFa production in an ex vivo inflammation model. Study design: Pharmacokinetic study, ex vivo experimental study. Methods: Six healthy adult horses of mixed breeds were used. In phase one, horses were given 5 lg/kg misoprostol orally, and blood was collected at predetermined times for determination of misoprostol free acid (MFA) by UHPLC-MS/MS. Pharmacokinetic parameters were calculated. In phase two, horses were dosed as in phase one, and blood was collected at T0, 0.5, 1 and 4 h following misoprostol administration for leucocyte isolation. Leucocytes were stimulated with 100 ng/mL LPS, and TNFa mRNA concentrations were determined via quantitative real-time PCR. Results: About 5 lg/kg oral misoprostol produced a rapid time to maximum concentration (T max) of 23.4 AE 2.4 min, with a maximum concentration (C max) of 0.29 AE 0.07 ng/mL and area under the curve (AUC 0À∞) of 0.4 AE 0.12 h ng/mL. LPS stimulation of equine leucocytes ex vivo significantly increased TNFa mRNA concentrations, and there was no significant effect of misoprostol even at the T max. Main limitations: Only a single dose was used, and sample size was small. Conclusions: Misoprostol is rapidly absorbed following oral administration in horses, and a single 5 lg/kg dose had no significant inhibitory effect on ex vivo LPS-stimulated TNFa mRNA production in leucocytes. Further studies analysing different dosing strategies, including repeat administration or combination with other anti-inflammatory drugs, are warranted.

Section: Discussionmentioning

confidence: 99%

“…Horses were housed in box stalls beginning 24 h prior to drug administration and for the duration of the study. They were offered free choice water and hay with the exception that horses were fasted prior to misoprostol administration . To fast the horses, hay was removed 12 h prior to and 2 h after administration of misoprostol.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and ex vivo anti‐inflammatory effects of oral misoprostol in horses

Martin

Schirmer

Jones

et al. 2018

“…Omeprazole, a substituted benzimidazole, is a potent inhibitor of gastric acid secretion in humans, rats, dogs and horses (Larsson et a1 1983;Lind et a1 1983;Sangiah, MacAllister and Amouzadeh 1989). Omeprazole acts by blocking the H+,K+-ATPase enzyme which is responsible for the final step in the production of hydrogen ions by the gastric parietal cell (Lindberg, Brgndstrilm and Wallmark 1987;Wallmark 1989).…”

Section: Introductionmentioning

confidence: 99%

Duration of antisecretory effects of oral omeprazole in horses with chronic gastric cannulae

Jenkins¹,

Blackford

Andrews

et al. 1992

Summary Eight female horses with chronic gastric cannulae were given omeprazole as enteric‐coated granules (1.4 mg/kg bwt) via nasogastric tube once daily for 6 days. The effects on basal and pentagastrin‐stimulated gastric acid secretion were determined 5 h after dosing on Days 1 and 5 ofadministration. A third gastric secretion test was done on Day 7, 24 h after the dose on Day 6. Gastric juice volume, pH, acidity, and acid output were determined during a 1‐h basal secretion test followed by a 2‐h pentagastrin‐stimulated (6 μg kg−1 h−1) test. When compared with placebo controls, omeprazole significantly inhibited basal gastric acid output by 72% and pentagastrin‐stimulated acid output by 86% on Day 5. Gastric juice pH was also significantly increased. On Day 7, basal gastric acid output was significantly decreased by 90% and pentagastrin‐stimulated secretion was decreased by 72%. The effect of omeprazole administration on gastric juice volume was variable. Once daily administration of 1.4 mg omeprazole/kg bwt significantly inhibited basal and stimulated gastric acid secretion in horses by the 5th dose. Gastric acid secretion was significantly inhibited for at least 27 h after omeprazole treatment, indicating a long duration of antisecretory effect of the drug in horses.

“…Using a treatment regimen previously shown to reduce gastric pH and free acid contents in the horse [7], no evidence of adverse effects of misoprostol treatment on mid‐gestation pregnancies of mares was observed. Cervical tone, ultrasonographic character of the conceptus, progesterone and oestrone sulphate concentrations, as well as observations of general health and comfort, all revealed no differences between misoprostol‐treated and control mares.…”

Section: Discussionmentioning

confidence: 94%

Mid‐gestation pregnancy is not disrupted by a 5‐day gastrointestinal mucosal cytoprotectant oral regimen of misoprostol

Jacobson

Sertich

2012