Pharmacokinetics of intravenous, plain oral and enteric‐coated oral omeprazole in the horse

Sykes, B. W.; Underwood, Charlie J.; McGowan, Catherine; Mills, P. C.

doi:10.1111/jvp.12169

Cited by 35 publications

(67 citation statements)

References 19 publications

(45 reference statements)

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“…The magnitude of the effect observed for the enteric coated formulation is similar to a recent report [100].…”

Section: Discussionsupporting

confidence: 90%

“…As such, commercial formulations of the drug typically incorporate some form of protection such as buffering with a highly alkaline medium, or the use of enteric coated granules suspended in a paste. A recent study reported the bioavailability of an enteric coated granule formulation (Gastrozol ® ) to be approximately twice that of a compounded, plain, unprotected omeprazole [100] supporting this recommendation.…”

Section: Introductionmentioning

confidence: 94%

“…Sample extraction was performed using protein precipitation extraction and plasma omeprazole concentration was determined by UHPLC-MS analysis as recently described [100]. The magnitude of intra-run variability was determined by calculating the coefficient of variation of the values for the replicates of the calibration curve samples determined at the beginning, middle and end of each run.…”

Section: Sample Extraction and Determination Of Plasma Omeprazole Conmentioning

confidence: 99%

“…However, this study was complicated in that the horses in the fasted state had already received five doses of omeprazole, and were compared to horses in the fed state after their first and fourteenth doses [3]. In contrast, a recent study investigating the pharmacokinetics of a single dose of an enteric coated formulation of omeprazole reported that absorption in fed animals was not significantly reduced compared to fasted animals [100]. These findings suggested that the effect of feeding may be, at least in part, dependent on the formulation used.…”

Section: Introductionmentioning

confidence: 99%

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Factors affecting the pharmacokinetics and pharmacodynamics of omeprazole in the horse

Sykes¹

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Equine Gastric Ulcer Syndrome (EGUS) is a common condition of the horse, affecting a broad range of horse usages and types. Recently the terminology of the syndrome has been expanded to include terms Equine Squamous Gastric Disease (ESGD) and Equine Glandular Gastric Disease (EGGD) to describe diseases of the squamous and glandular mucosa of the stomach, respectively. Omeprazole, a proton pump inhibitor that blocks acid production, is considered the treatment of choice for EGUS and it has been widely used for this purpose for nearly 20 years. Yet, surprisingly, despite its widespread use little is known about the factors that affect its efficacy, such as the impact of formulation, diet and dose. Further, although it is commonly believed that the once daily administration of omeprazole results in durations of acid suppression exceeding 24 hours, there is conflict in the literature as to the validity of this belief. Recent clinical studies have demonstrated that the healing rate for EGGD is inferior to that of ESGD, raising further questions as to the efficacy of omeprazole under clinically relevant conditions. One potential reason for this observation is that the duration of intra-day acid suppression required for healing of ESGD may be less than that for EGGD. This, coupled with the possibility that once daily administration of omeprazole may not result in acid suppression for the entire 24 hour treatment interval, provides a potential explanation for the poor EGGD healing rates that have been recently reported. The purpose of this thesis was to investigate the factors that affect the efficacy of omeprazole in the horse. The studies were conducted in four parts; firstly, the effect of formulation and diet on the pharmacokinetics of omeprazole were investigated; secondly, a model that allows continuous intra-gastric pH measurement under clinically relevant conditions was developed; thirdly, the impact of diet and dose on the pharmacokinetics and pharmacodynamics of omeprazole were investigated; and lastly, the relationships between key pharmacokinetic and pharmacodynamic variables were investigated. The findings of the study suggested that some method of physical protection is required to protect the omeprazole from degradation in the acidic environment of the stomach and to improve bioavailability. However, significant differences were not present between formulations utilising the two most common forms of protection, namely the use of enteric coated granules in paste or buffering of the formulation. This suggests that the method of protection, buffering of the formulation or the use enteric coated granules in paste, used is less important than protection per se. The earlier studies of the thesis 3 suggested that an effect of feeding may be present on the pharmacokinetics of omeprazole but a statistically significant effect could not be demonstrated. Similarly, the latter studies suggested that diet may play a role in bioavailability with ad libitum roughage diets impairing absorption, but no statistically signi...

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“…The magnitude of the effect observed for the enteric coated formulation is similar to a recent report [100].…”

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 94%

Section: Sample Extraction and Determination Of Plasma Omeprazole Conmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Factors affecting the pharmacokinetics and pharmacodynamics of omeprazole in the horse

Sykes¹

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“…The bioavailability of oral enteric coated omeprazole is variable but unaffected by feeding or fasting [16]. Withdrawal of omeprazole after 56 days of treatment has been reported as resulting in a rapid return of gastric ulceration [15].…”

Section: Introductionmentioning

confidence: 99%

A Comparison Between Omeprazole and a Dietary Supplement for the Management of Squamous Gastric Ulceration in Horses

Kerbyson

Knottenbelt

Carslake

et al. 2016

Journal of Equine Veterinary Science

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Although several studies have assessed the short-term effect of dietary supplements on the treatment and prevention of gastric ulceration in horses, few have assessed the response over a duration of more than 30 days. 2A blinded randomised non-inferiority clinical trial was conducted using forty-two Thoroughbred horses in race training with squamous ulceration of ≥ grade 2/4, randomly assigned to one of two treatment groups for a period of 90 days: omeprazole at the full label dose of 4mg/kg or the Succeed® digestive conditioning supplement. Non-inferiority analyses and Wilcoxon sign rank tests were used to analyse the data.At day 90, Succeed® was non-inferior to 4mg/kg omeprazole administered daily in terms of the proportion of horses with complete resolution of squamous ulceration.At day 30, Succeed® was found to be inferior to omeprazole in terms of the proportion of horses with grade ≤1/4 squamous ulceration. The proportion of horses with reducing squamous ulcer score (compared with day 0) was statistically significant for both treatments at days 30 and 60. At day 90 of the 17 horses on Succeed®, nine had a reducing squamous ulcer score (p-value = 0.049) and of the 19 horses on omeprazole, 10 had a reducing squamous ulcer score at day 90 (p-value = 0.091).The non-inferiority of Succeed® compared to omeprazole at 90 days for the complete resolution of squamous ulceration and the reduced efficacy of omeprazole following 90 days of treatment are likely to be of interest to practitioners managing gastric ulceration in performance horses.

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A study investigating the treatment of equine squamous gastric disease with long‐acting injectable or oral omeprazole

Gough¹,

Hallowell

Rendle³

2020

Veterinary Medicine & Sci

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Background: Equine squamous gastric disease (ESGD) is a highly prevalent disease in horses, particularly in elite athletes. Some horses respond slowly, or fail to respond, to the licensed treatment, oral omeprazole (ORLO). Objectives:To compare rates of ESGD healing and improvement between ORLO and a long-acting injectable omeprazole preparation (LAIO). Study design: Retrospective clinical study. Methods: The case records and gastroscopy images of horses presenting to Rainbow Equine Hospital over a 12-month period were reviewed, with images being reviewed blind by one of the authors (David Rendle). Treatment responses were compared between horses that received 2 or 4 injections of 4 mg/kg LAIO at weekly intervals, and horses that received ORLO at 4 mg/kg PO SID for 4 weeks. Data were compared using a Mann-Whitney test with post hoc Dunn's test, chi-squared test or Fisher's exact test. Results: Fifty-six horses met the inclusion criteria: 29 received LAIO and 27 received ORLO. Treatment groups were comparable in terms of signalment and ESGD lesions.There was a difference in rate of healing when LAIO and ORLO treatment groups were compared at 28 days (LAIO-97%; ORLO-67%; p = .005; OR = 14(1.8-158)), but no difference between LAIO at 14 days and ORLO at 28 days (LAIO-86%; ORLO-67%; p = .12; OR = 3.1 (0.9-10)). Five localised and self-limiting injection site reactions were identified in 3 horses out of 98 injections (5.1%). Main limitations:The study was limited by its retrospective nature, absence of randomisation and limited numbers. Conclusions:Four weeks of treatment with LAIO resulted in better rates of ESGD healing than 4 weeks of ORLO. Larger more robust studies of LAIO are warranted. K E Y W O R D S gastrointestinal, horse, proton pump inhibitor, stomach How to cite this article: Gough S, Hallowell G, Rendle D.A study investigating the treatment of equine squamous gastric disease with long-acting injectable or oral omeprazole.

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Pharmacokinetics of intravenous, plain oral and enteric‐coated oral omeprazole in the horse

Cited by 35 publications

References 19 publications

Factors affecting the pharmacokinetics and pharmacodynamics of omeprazole in the horse

Factors affecting the pharmacokinetics and pharmacodynamics of omeprazole in the horse

A Comparison Between Omeprazole and a Dietary Supplement for the Management of Squamous Gastric Ulceration in Horses

A study investigating the treatment of equine squamous gastric disease with long‐acting injectable or oral omeprazole

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