TY - JOUR
T1 - Pharmacokinetic and pharmacodynamic effects of 2 registered omeprazole preparations and varying dose rates in horses
AU - Wise, Jessica C.
AU - Hughes, Kristopher J.
AU - Edwards, Scott
AU - Jacobson, Glenn A.
AU - Narkowicz, Christian K.
AU - Raidal, Sharanne L.
N1 - Funding Information:
Funding was provided by Equestra Pty Ltd, 111 Hume St Wodonga, Victoria, Australia. The authors acknowledge Sharon Nielson Statistical Consulting and Training for the input in statistical analysis, including all the bioequivalence statistics. Presented as an ePoster at the 2020 ACVIM Forum On Demand.
Publisher Copyright:
© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/1
Y1 - 2021/1/1
N2 -
Background
Omeprazole preparations vary in bioavailability in horses.
Hypothesis/Objectives
To characterize the pharmacokinetics and
pharmacodynamics of an existing enteric-coated oral omeprazole paste
(REF) and a novel, in-feed, enteric-coated dry granule preparation
(NOV).
Animals
Twelve Standardbred/Thoroughbred mares free from clinical disease.
Methods
A prospective, blinded randomized interventional study
was trial, conducted in 3 parts: (a) bioavailability study, (b) dose
titration study, and (c) comparative clinical pharmacodynamic study,
each using a blocked crossover design.
Results
Consistent with the larger dose administered, Cmax
(median, 1032 ng/mL; range, 576-1766) and AUC0-24 (median, 63.9
μg/mL*min; range, 42.4-152.4) were greater after single oral
administration of NOV than REF (282.7 ng/mL; range, 94.8-390.2, and 319
23.8 μg/mL*min; range, 8.2-42.3, respectively; both P = .004). No
differences were observed between products for absolute oral
bioavailability (NOV 55% range, 15-88; REF 17% range, 10-77; P =
.25). Treatment with both preparations was associated with reduced
gastric squamous ulcer scores and increased pH of gastric fluid.
Bioequivalence was demonstrated for pharmacodynamic measures with the
exception of % time pH <4, despite differences in dose rate and
subsequent plasma omeprazole concentrations.
Conclusions and Clinical Importance
The findings of this study indicate that the NOV
product would be a suitable alternative to the reference product, and
confirm that plasma concentrations of omeprazole and omeprazole dose do
not predict drug pharmacodynamics in horses.
AB -
Background
Omeprazole preparations vary in bioavailability in horses.
Hypothesis/Objectives
To characterize the pharmacokinetics and
pharmacodynamics of an existing enteric-coated oral omeprazole paste
(REF) and a novel, in-feed, enteric-coated dry granule preparation
(NOV).
Animals
Twelve Standardbred/Thoroughbred mares free from clinical disease.
Methods
A prospective, blinded randomized interventional study
was trial, conducted in 3 parts: (a) bioavailability study, (b) dose
titration study, and (c) comparative clinical pharmacodynamic study,
each using a blocked crossover design.
Results
Consistent with the larger dose administered, Cmax
(median, 1032 ng/mL; range, 576-1766) and AUC0-24 (median, 63.9
μg/mL*min; range, 42.4-152.4) were greater after single oral
administration of NOV than REF (282.7 ng/mL; range, 94.8-390.2, and 319
23.8 μg/mL*min; range, 8.2-42.3, respectively; both P = .004). No
differences were observed between products for absolute oral
bioavailability (NOV 55% range, 15-88; REF 17% range, 10-77; P =
.25). Treatment with both preparations was associated with reduced
gastric squamous ulcer scores and increased pH of gastric fluid.
Bioequivalence was demonstrated for pharmacodynamic measures with the
exception of % time pH <4, despite differences in dose rate and
subsequent plasma omeprazole concentrations.
Conclusions and Clinical Importance
The findings of this study indicate that the NOV
product would be a suitable alternative to the reference product, and
confirm that plasma concentrations of omeprazole and omeprazole dose do
not predict drug pharmacodynamics in horses.
KW - bioavailability
KW - enteric-coated omeprazole
KW - gastric ulcer healing
KW - gastric ulcers
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U2 - 10.1111/jvim.15971
DO - 10.1111/jvim.15971
M3 - Article
C2 - 33340169
AN - SCOPUS:85097768290
VL - 35
SP - 620
EP - 631
JO - Journal of Veterinary Internal Medicine
JF - Journal of Veterinary Internal Medicine
SN - 0891-6640
IS - 1
ER -