School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia.
School of Pharmacy and Pharmacology, University of Tasmania, Hobart, Tasmania, Australia.
J Vet Intern Med. 2021 Jan;35(1):620-631. doi: 10.1111/jvim.15971. Epub 2020 Dec 19.
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).
Twelve Standardbred/Thoroughbred mares free from clinical disease.
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.
Consistent with the larger dose administered, Cmax (median, 1032 ng/mL; range, 576-1766) and AUC0-24 (median, 63.9 μg/mLmin; 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/mLmin; 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.
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.
奥美拉唑制剂在马体内的生物利用度存在差异。
假设/目的：描述一种现有的肠溶口服奥美拉唑糊剂（REF）和一种新型、饲用、肠溶干颗粒制剂（NOV）的药代动力学和药效动力学特征。
12 匹无临床疾病的标准bred/thoroughbred 母马。
进行了一项前瞻性、双盲、随机干预研究，分为 3 部分：（a）生物利用度研究，（b）剂量滴定研究，（c）比较临床药效动力学研究，每个部分均采用交叉设计。
单次口服 NOV 后，Cmax（中位数，1032ng/ml；范围，576-1766）和 AUC0-24（中位数，63.9μg/mlmin；范围，42.4-152.4）均大于 REF（282.7ng/ml；范围，94.8-390.2，和 319 23.8μg/mlmin；范围，8.2-42.3，均 P =.004）。两种制剂的绝对口服生物利用度无差异（NOV 55%，范围 15-88；REF 17%，范围 10-77；P =.25）。两种制剂治疗均与胃鳞状溃疡评分降低和胃液 pH 值升高相关。尽管剂量率和随后的奥美拉唑血浆浓度存在差异，但药效学指标的生物等效性得到了证实，除外 pH 值<4 的时间百分比。
本研究结果表明，NOV 产品将是 REF 产品的合适替代品，并证实了马的奥美拉唑血浆浓度和剂量并不预测药物药效动力学。
