Reilley Sandra, Wenzel Eric, Reynolds Laurie, Bennett Beth, Patti Joseph M, Hetherington Seth
Northwest Kinetics, Tacoma, Washington, USA.
Antimicrob Agents Chemother. 2005 Mar;49(3):959-62. doi: 10.1128/AAC.49.3.959-962.2005.
Tefibazumab (Aurexis) is a humanized monoclonal antibody being evaluated as adjunctive therapy for the treatment of Staphylococcus aureus infections. This open-label, dose escalation study evaluated the safety and pharmacokinetics of tefibazumab in 19 healthy volunteers aged 18 to 69 years. Each subject received a single administration of tefibazumab at a dose of 2, 5, 10, or 20 mg/kg of body weight infused over 15 min. Plasma samples for pharmacokinetic assessments were obtained before infusion as well as 1, 6, 12, and 24 h and 3, 4, 7, 21, 28, 42, and 56 days after dosing. Plasma concentrations of tefibazumab were detected 1 h after the end of the infusion, with a mean maximum concentration of drug in serum (C(max)) of 59, 127, 252, and 492 microg/ml following doses of 2, 5, 10, and 20 mg/kg, respectively. The median time to maximum concentration of drug in serum (T(max)) was 1.0 h for each dose. The mean elimination half-life (t(1/2)) was approximately 22 days. The volume of distribution (V) was 4.7, 6.7, 7.2, and 7.2 liters after doses of 2, 5, 10, and 20 mg/kg, respectively. Clearance (CL) was 6.0, 9.2, 10.2, and 9.9 ml/hr, respectively. At the highest dose, plasma levels of tefibazumab were >100 microg/ml for 21 days. On day 56, the mean plasma concentrations were 6.3, 10.0, 16.4, and 30.5 microg/ml for the 2, 5, 10, and 20 mg/kg doses, respectively. Tefibazumab exhibited linear kinetics across doses of 5, 10, and 20 mg/kg. No anti-tefibazumab antibodies were detected after dosing in any subject. There were no serious adverse events, and tefibazumab was well tolerated over the entire dose range.
替非巴珠单抗（奥瑞希斯）是一种人源化单克隆抗体，正作为辅助疗法用于治疗金黄色葡萄球菌感染。这项开放标签、剂量递增研究评估了替非巴珠单抗在19名年龄在18至69岁的健康志愿者中的安全性和药代动力学。每名受试者接受一次替非巴珠单抗静脉输注，剂量分别为2、5、10或20mg/kg体重，输注时间为15分钟。在输注前以及给药后1、6、12和24小时以及3、4、7、21、28、42和56天采集用于药代动力学评估的血浆样本。输注结束1小时后检测到替非巴珠单抗的血浆浓度，剂量为2、5、10和20mg/kg时，血清中药物的平均最大浓度（C(max)）分别为59、127、252和492μg/ml。各剂量血清中药物达到最大浓度的中位时间（T(max)）均为1.0小时。平均消除半衰期（t(1/2)）约为22天。剂量为2、5、10和20mg/kg后，分布容积（V）分别为4.7、6.7、7.2和7.2升。清除率（CL）分别为6.0、9.2、10.2和9.9ml/小时。在最高剂量时，替非巴珠单抗的血浆水平在21天内>100μg/ml。在第56天，2、5、10和20mg/kg剂量的平均血浆浓度分别为6.3、10.0、16.4和30.5μg/ml。替非巴珠单抗在5、10和20mg/kg剂量范围内呈现线性动力学。给药后在任何受试者中均未检测到抗替非巴珠单抗抗体。未发生严重不良事件，替非巴珠单抗在整个剂量范围内耐受性良好。
