Salyards Gregory W, Knych Heather K, Hill Ashley E, Kelly Kristi R, Christe Kari L
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.
J Am Assoc Lab Anim Sci. 2015 Sep;54(5):557-63.
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.
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。