Boegel Annette, Flamme Ingo, Krebber Ralph, Settje Terry, Schmidt Franziska, Kruedewagen Eva, Mangold-Gehring Sandra, Lainesse Chantal, Moritz Andreas, Beddies Gerald
Elanco Animal Health, Leverkusen, Germany.
Bayer AG, Leverkusen, Germany.
J Vet Intern Med. 2024 Jan-Feb;38(1):381-387. doi: 10.1111/jvim.16827. Epub 2023 Nov 23.
Inhibition of hypoxia-inducible factor prolyl hydroxylase (HIF-PH) stimulates erythropoiesis in rats, dogs, monkeys, and humans.
HYPOTHESIS/OBJECTIVE: Determine if molidustat, a novel HIF-PH inhibitor, stimulates erythropoiesis in healthy cats.
Seventeen healthy adult laboratory cats.
Randomized, placebo-controlled study. Cats were treated PO once daily with suspensions of 0 (Group 1; n = 6), 5 (Group 2; n = 6), or 10 (Group 3; n = 5) mg/kg of molidustat. Effects on red blood cell parameters, reticulocyte indices and plasma erythropoietin (EPO) concentrations were evaluated. Molidustat treatment was stopped when hematocrit (HCT) exceeded 60%.
Compared to placebo, a significant increase in mean HCT was evident starting on Day 14 (Group 2:54.4% vs 40.3%, P < .001, 95% confidence interval [CI] for the difference [8.95-19.28]; Group 3:61.2% vs 40.3%, P < .001, 95% CI [15.48-26.43]) and remained significantly higher for the entire treatment period. In molidustat-treated groups, HCT exceeded 60% on Day 21 (Group 2) and Day 14 (Group 3). Mean HCT in molidustat-treated cats returned to within the reference range (29%-45%) after Day 56 and was numerically comparable to placebo from Day 70 onwards. Red blood cell count and hemoglobin concentrations followed a similar pattern as HCT. Mean EPO concentrations significantly increased after molidustat administration on all assessment days. Molidustat treatments were well tolerated.
Marked erythropoietic effects were identified after daily administration of molidustat to healthy cats and additional studies are warranted to evaluate the effects in anemic cats.
抑制缺氧诱导因子脯氨酰羟化酶（HIF-PH）可刺激大鼠、犬、猴和人类的红细胞生成。
假设/目的：确定新型HIF-PH抑制剂莫利度司他是否能刺激健康猫的红细胞生成。
17只健康成年实验猫。
随机、安慰剂对照研究。猫每天口服一次0（第1组；n = 6）、5（第2组；n = 6）或10（第3组；n = 5）mg/kg莫利度司他的混悬液。评估对红细胞参数、网织红细胞指数和血浆促红细胞生成素（EPO）浓度的影响。当血细胞比容（HCT）超过60%时停止莫利度司他治疗。
与安慰剂相比，从第14天开始平均HCT显著增加（第2组：54.4%对40.3%，P <.001，差异的95%置信区间[CI][8.95 - 19.28]；第3组：61.2%对40.3%，P <.001，95% CI[15.48 - 26.43]），并且在整个治疗期间一直显著更高。在莫利度司他治疗组中，第21天（第2组）和第14天（第3组）HCT超过60%。莫利度司他治疗的猫的平均HCT在第56天后恢复到参考范围内（29% - 45%），并且从第70天起在数值上与安慰剂相当。红细胞计数和血红蛋白浓度的变化模式与HCT相似。在所有评估日，莫利度司他给药后平均EPO浓度显著增加。莫利度司他治疗耐受性良好。
对健康猫每日给予莫利度司他后发现有明显的促红细胞生成作用，有必要进行进一步研究以评估其对贫血猫的影响。
