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重组羊干扰素-tau在羔羊体内的药代动力学

Pharmacokinetics of the recombinant ovine interferon-tau in lambs.

作者信息

Zhao J, Yu H Y, Zhao Y, Li S Q, Fu X L, Zhou W, Xia B B, Wang M L, Chen J

机构信息

Department of Microbiology, Anhui Medical University, Hefei, Anhui Province, 230032, China.

Anhui JiuChuan Biotech Co., Ltd., Wuhu, Anhui Province, 241007, China.

出版信息

Pol J Vet Sci. 2019 Mar;22(1):75-82. doi: 10.24425/pjvs.2018.125610.

DOI:10.24425/pjvs.2018.125610
PMID:30997764
Abstract

In the current study, twenty lambs, aged 4 months, half male and half female, were classified into four groups, with five in each group. The experimental three groups of lambs were given intravenous (IV), intramuscular (IM) and subcutaneous (SC) administrations of recombinant ovine interferon-τ (roIFN-τ). The fourth group (normal control) of lambs was given normal saline injections in the same way. After administrations, blood samples were collected from the tested animals at different time points post injection, and the serum titers of roIFN-τ were measured using cytopathic effect (CPE) inhibition bioassay. The results of calculating pharmacokinetic (PK) parameters using DAS software showed that the PK characteristics of roIFN-τ through IV injection conformed to the two-compartment open model, whose half-life of distribution phases (T1/2α) was 0.33±0.034 h and the elimination half-life(T1/2β) was 5.01±0.24 h. However, the PK features of IM injection and SC injection of roIFN-τ conformed to the one compartment open model, whose Tmax were 3.11±0.26 h and 4.83±0.43 h, respectively, together with an elimination half life(T1/2β) of 9.11±0.76 h and 7. 43±0.58 h, and an absorption half-life (T1/2k(a)) of 1.13±0.31 h and 1.85±0.40 h, respectively. The bioavailability of roIFN-τ after IM administration reaches 73.57%, which is greater than that of SC administration (53.43%). These results indicate that the drug administration effect can be preferably obtained following a single dose IM administration of the roIFN-τ aqueous preparation. This study will facilitate the clinical application of roIFN-τ as a potential antiviral agent in future work.

摘要

在本研究中,选用20只4月龄羔羊,雌雄各半,分为四组,每组5只。对实验的三组羔羊分别进行重组羊干扰素-τ(roIFN-τ)的静脉注射(IV)、肌肉注射(IM)和皮下注射(SC)。第四组(正常对照组)羔羊以同样方式注射生理盐水。给药后,在注射后的不同时间点从受试动物采集血样,采用细胞病变效应(CPE)抑制生物测定法测定roIFN-τ的血清效价。使用DAS软件计算药代动力学(PK)参数的结果表明,roIFN-τ静脉注射的PK特征符合二室开放模型,其分布相半衰期(T1/2α)为0.33±0.034小时,消除半衰期(T1/2β)为5.01±0.24小时。然而,roIFN-τ肌肉注射和皮下注射的PK特征符合一室开放模型,其达峰时间(Tmax)分别为3.11±0.26小时和4.83±0.43小时,消除半衰期(T1/2β)分别为9.11±0.76小时和7.43±0.58小时,吸收半衰期(T1/2k(a))分别为1.13±0.31小时和1.85±0.40小时。roIFN-τ肌肉注射后的生物利用度达到73.57%,高于皮下注射(53.43%)。这些结果表明,单次肌肉注射roIFN-τ水剂可较好地获得给药效果。本研究将有助于roIFN-τ作为一种潜在抗病毒药物在未来工作中的临床应用。

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