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头孢噻呋晶体游离酸在雄性恒河猴(猕猴)皮下注射后的药代动力学

Pharmacokinetics of Ceftiofur Crystalline Free Acid in Male Rhesus Macaques (Macaca mulatta) after Subcutaneous Administration.

作者信息

Salyards Gregory W, Knych Heather K, Hill Ashley E, Kelly Kristi R, Christe Kari L

机构信息

Department of Primate Medicine, California National Primate Research Center, Davis, Davis, California, USA.

KL Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.

出版信息

J Am Assoc Lab Anim Sci. 2015 Sep;54(5):557-63.

Abstract

Trauma is a common sequela to agonistic social encounters in rhesus macaques (Macaca mulatta), and veterinarians often prescribe antibiotics as part of a balanced treatment plan. Long-acting, single-dose, injectable antibiotics for use in rhesus macaques are unavailable currently. Ceftiofur crystalline free acid (CCFA) is a long-acting, single-dose, injectable third-generation cephalosporin that provides at least 7 d of ceftiofur therapeutic plasma concentrations in swine (Sus scrofa domesticus). We hypothesized that CCFA would achieve similar therapeutic concentrations (≥ 0.2 μg/mL) in rhesus macaques. We describe the pharmacokinetic profile of CCFA in healthy, adult male rhesus macaques ( n = 6) in this 2-period, 2-treatment crossover study of 5 and 20 mg/kg SC administered once. Plasma ceftiofur metabolite concentrations were determined prior to and for a maximum of 21 d after administration. Noncompartmental pharmacokinetic analysis was performed. The 5-mg dose achieved a maximal plasma concentration of 2.24 ± 0.525 μg/mL at 2.59 ± 1.63 h, an AUC of 46.9 ± 17.6 h/μg/mL, and a terminal elimination half-life of 56.5 ± 21.7 h; for the 20-mg/kg dose, these parameters were 9.18 ± 4.90 μg/mL at 1.82 ± 1.30 h, 331 ± 84.4 h/μg/mL, and 69.7 ± 8.86 h, respectively. No adverse effects were noted after either dose. Macaques maintained plasma ceftiofur concentrations of 0.2 μg/mL or greater for at least 2 d after 5 mg/kg SC and at least 7 d after 20 mg/kg SC.

摘要

创伤是恒河猴(猕猴属)发生争斗性社交接触后的常见后遗症,兽医通常会将抗生素作为平衡治疗方案的一部分进行处方。目前尚无用于恒河猴的长效、单剂量注射用抗生素。头孢噻呋晶体游离酸(CCFA)是一种长效、单剂量注射用第三代头孢菌素,在猪(家猪)体内可提供至少7天的头孢噻呋治疗性血浆浓度。我们假设CCFA在恒河猴体内能达到相似的治疗浓度(≥0.2μg/mL)。在这项2期、2治疗交叉研究中,我们描述了CCFA在6只健康成年雄性恒河猴体内的药代动力学特征,分别单次皮下注射5mg/kg和20mg/kg。在给药前及给药后最多21天测定血浆头孢噻呋代谢物浓度。进行了非房室药代动力学分析。5mg/kg剂量在2.59±1.63小时达到最大血浆浓度2.24±0.525μg/mL,曲线下面积为46.9±17.6h/μg/mL,末端消除半衰期为56.5±21.7小时;20mg/kg剂量的这些参数分别为在1.82±1.30小时达到9.18±4.90μg/mL,331±84.4h/μg/mL,以及69.7±8.86小时。两种剂量给药后均未观察到不良反应。5mg/kg皮下注射后,恒河猴血浆头孢噻呋浓度维持在0.2μg/mL或更高至少2天;20mg/kg皮下注射后至少维持7天。

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