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口服泛昔洛韦治疗禽类系统性等孢子虫病的药代动力学和药效学。

THE PHARMACOKINETICS AND PHARMACODYNAMICS OF ORAL PONAZURIL IN THE TREATMENT OF SYSTEMIC ISOSPOROSIS IN PASSERINE BIRDS.

机构信息

Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois at Champaign-Urbana, Urbana, IL 61802, USA,

Zoological Pathology Program, University of Illinois, Brookfield, IL 60513, USA.

出版信息

J Zoo Wildl Med. 2023 Oct;54(3):561-572. doi: 10.1638/2022-0091.

DOI:10.1638/2022-0091
PMID:37817622
Abstract

Systemic isosporosis, previously atoxoplasmosis, is a significant cause of mortality in juvenile passerine birds. Recommended treatment regimens are empiric and vary in efficacy. The goal of this study was to determine the pharmacokinetics and pharmacodynamics of ponazuril for treatment of systemic isosporosis. Ponazuril, diluted with water to create an oral suspension (50 mg/ml), was administered (100 mg/kg) to 72 European starlings () by a single dose via direct oral gavage (n = 24), a single dose injected into superworm larvae (; n = 24), or a daily dose mixed with commercial dog food to top-dress feed for 5 d (n = 24). Peak plasma concentrations were 5.84, 2.46, and 9.13 µg/ml for the direct gavage, injected larvae, and top-dressed feed groups, respectively. With repeated dosing, mean plasma concentrations from the top-dressed feed group were maintained between 8.12 to 13.11 µg/ml. Results suggested ponazuril at a dosage of 100 mg/kg administered via direct gavage or top-dressed feed, but not via injected larvae, would exceed the concentrations needed to inhibit merogony of other apicomplexan parasites in cell culture (5 µg/ml). To assess the pharmacodynamics of this dose, seven passerine birds, red-vented bulbuls (; n = 2), blue-grey tanager (; n = 1), and red-capped cardinals (; n = 4), were identified as shedders of systemic spp. via fecal qPCR. Birds were then treated with ponazuril (100 mg/kg) daily on top-dressed feed for 14 d. Fecal shedding was assessed via qPCR for 6 wk from the initiation of treatment. Treatment was associated with reduction in proportions of fecal shedding during the treatment period and the week following treatment, but shedding resumed in all birds by the end of sampling. Results support that treatment of breeding birds with 100 mg/kg ponazuril could reduce the shedding of active oocysts and decrease risk of clinical infection in susceptible juveniles.

摘要

系统性等孢子虫病,以前称为弓形体病,是幼鸟死亡率的重要原因。推荐的治疗方案是经验性的,疗效各不相同。本研究的目的是确定地克珠利治疗系统性等孢子虫病的药代动力学和药效学。地克珠利用稀释水制成口服混悬液(50mg/ml),通过单次经口灌胃(n=24)、单次注射到超级幼虫(n=24)或每天与商业狗粮混合,在 5 天内上药喂食(n=24),向 72 只欧洲椋鸟()中给予 100mg/kg 的剂量。直接灌胃、注射幼虫和上药喂食组的血药峰浓度分别为 5.84、2.46 和 9.13µg/ml。重复给药后,上药喂食组的平均血药浓度维持在 8.12 至 13.11µg/ml 之间。结果表明,以 100mg/kg 的剂量经口灌胃或上药喂食,而不是通过注射幼虫给予地克珠利,将超过抑制细胞培养中其他顶复门寄生虫裂殖的浓度(5µg/ml)。为了评估该剂量的药效动力学,通过粪便 qPCR 鉴定了 7 只 passerine 鸟类(红腹凤头鹦鹉(),2 只;蓝灰唐纳雀(),1 只;红帽知更鸟(),4 只)为系统性 spp.的脱落者。然后,这些鸟类用地克珠利(100mg/kg)每天在上药喂食中治疗 14 天。从治疗开始,通过 qPCR 评估粪便脱落情况,持续 6 周。治疗与治疗期间和治疗后一周粪便脱落比例降低有关,但所有鸟类在采样结束时都恢复了脱落。结果支持在繁殖鸟类中使用 100mg/kg 地克珠利可以减少活性卵囊的脱落,并降低易感幼鸟的临床感染风险。

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