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皮下注射阿糖胞苷联合泼尼松在病因不明的脑膜脑脊髓炎犬中的药代动力学。

The pharmacokinetics of cytarabine administered subcutaneously, combined with prednisone, in dogs with meningoencephalomyelitis of unknown etiology.

作者信息

Pastina B, Early P J, Bergman R L, Nettifee J, Maller A, Bray K Y, Waldron R J, Castel A M, Munana K R, Papich M G, Messenger K M

机构信息

College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina.

Carolina Veterinary Specialists, Matthews, North Carolina.

出版信息

J Vet Pharmacol Ther. 2018 Oct;41(5):638-643. doi: 10.1111/jvp.12667. Epub 2018 May 15.

DOI:10.1111/jvp.12667
PMID:29761906
Abstract

The objective of this study was to describe the pharmacokinetics (PK) of cytarabine (CA) after subcutaneous (SC) administration to dogs with meningoencephalomyelitis of unknown etiology (MUE). Twelve dogs received a single SC dose of CA at 50 mg/m as part of treatment of MUE. A sparse sampling technique was used to collect four blood samples from each dog from 0 to 360 min after administration. All dogs were concurrently receiving prednisone (0.5-2 mg kg day ). Plasma CA concentrations were measured by HPLC, and pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling (NLME). Plasma drug concentrations ranged from 0.05 to 2.8 μg/ml. The population estimate (CV%) for elimination half-life and Tmax of cytarabine in dogs was 1.09 (21.93) hr and 0.55 (51.03) hr, respectively. The volume of distribution per fraction absorbed was 976.31 (10.85%) ml/kg. Mean plasma concentration of CA for all dogs was above 1.0 μg/ml at the 30-, 60-, 90-, and 120-min time points. In this study, the pharmacokinetics of CA in dogs with MUE after a single 50 mg/m SC injection in dogs was similar to what has been previously reported in healthy beagles; there was moderate variability in the population estimates in this clinical population of dogs.

摘要

本研究的目的是描述对病因不明的脑膜脑脊髓炎(MUE)犬皮下注射阿糖胞苷(CA)后的药代动力学(PK)情况。12只犬接受了50mg/m的单次皮下注射CA,作为MUE治疗的一部分。采用稀疏采样技术在给药后0至360分钟从每只犬采集4份血样。所有犬同时接受泼尼松(0.5 - 2mg/kg/天)治疗。通过高效液相色谱法测定血浆CA浓度,并使用非线性混合效应模型(NLME)估算药代动力学参数。血浆药物浓度范围为0.05至2.8μg/ml。犬体内阿糖胞苷消除半衰期和达峰时间的群体估计值(CV%)分别为1.09(21.93)小时和0.55(51.03)小时。每吸收部分的分布容积为976.31(10.85%)ml/kg。在30、60、90和120分钟时间点,所有犬的CA平均血浆浓度均高于1.0μg/ml。在本研究中,犬单次皮下注射50mg/m的CA后,MUE犬体内CA的药代动力学与先前在健康比格犬中报道的相似;在该临床犬群体中,群体估计值存在中度变异性。

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