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新型环氧化酶-2选择性抑制剂维他昔布在猫体内的药代动力学:进食和剂量的影响。

Pharmacokinetics of the novel COX-2 selective inhibitor vitacoxib in cats: The effects of feeding and dose.

作者信息

Wang Jianzhong, Gong Xiaohui, Xue Jiao, Zhang Suxia, Li Jing, Cao Xingyuan

机构信息

Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing, China.

Laboratory of Quality & Safety Risk Assessment for Animal Products on Chemical Hazards (Beijing), Ministry of Agriculture and Rural affairs of the People's Republic of China, Beijing, China.

出版信息

J Vet Pharmacol Ther. 2019 May;42(3):294-299. doi: 10.1111/jvp.12751. Epub 2019 Feb 8.

Abstract

The purpose of this study was to determine the pharmacokinetics and dose-scaling model of vitacoxib in either fed or fasted cats following either oral or intravenous administration. The concentration of the drug was quantified by UPLC-MS/MS on plasma samples. Relevant parameters were described using noncompartmental analysis (WinNonlin 6.4 software). Vitacoxib is relatively slowly absorbed and eliminated after oral administration (2 mg/kg body weight), with a T of approximately 4.7 hr. The feeding state of the cat was a statistically significant covariate for both area under the concentration versus time curve (AUC) and mean absorption time (MAT ). The absolute bioavailability (F) of vitacoxib (2 mg/kg body weight) after oral administration (fed) was 72.5%, which is higher than that in fasted cats (F = 50.6%). Following intravenous administration (2 mg/kg body weight), Vd (ml/kg) was 1,264.34 ± 343.63 ml/kg and Cl (ml kg  hr ) was 95.22 ± 23.53 ml kg  hr . Plasma concentrations scaled linearly with dose, with C (ng/ml) of 352.30 ± 63.42, 750.26 ± 435.54, and 936.97 ± 231.27 ng/ml after doses of 1, 2, and 4 mg/kg body weight, respectively. No significant undesirable behavioral effects were noted throughout the duration of the study.

摘要

本研究的目的是确定维他昔布在喂食或禁食的猫经口服或静脉给药后的药代动力学和剂量缩放模型。通过超高效液相色谱-串联质谱法(UPLC-MS/MS)对血浆样本中的药物浓度进行定量。使用非房室分析(WinNonlin 6.4软件)描述相关参数。口服给药(2毫克/千克体重)后,维他昔布的吸收和消除相对较慢,T约为4.7小时。猫的进食状态对于浓度-时间曲线下面积(AUC)和平均吸收时间(MAT)而言均为具有统计学意义的协变量。口服给药(喂食)后,维他昔布(2毫克/千克体重)的绝对生物利用度(F)为72.5%,高于禁食猫(F = 50.6%)。静脉给药(2毫克/千克体重)后,分布容积(Vd,毫升/千克)为1264.34±343.63毫升/千克,清除率(Cl,毫升·千克⁻¹·小时⁻¹)为95.22±23.53毫升·千克⁻¹·小时⁻¹。血浆浓度与剂量呈线性关系,体重剂量分别为1、2和4毫克/千克时,C(纳克/毫升)分别为352.30±63.42、750.26±435.54和936.97±231.27纳克/毫升。在整个研究期间未观察到明显的不良行为影响。

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