AZD7442 (Evusheld) is a combination of two human anti-severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs), tixagevimab (AZD8895) and cilgavimab (AZD1061). Route of administration is an important consideration to improve treatment access. We assessed pharmacokinetics (PKs) of AZD7442 absorption following 600 mg administered intramuscularly (i.m.) in the thigh compared with 300 mg intravenously (i.v.) in ambulatory adults with symptomatic COVID-19. PK analysis included 84 of 110 participants randomized to receive i.m. AZD7442 and 16 of 61 randomized to receive i.v. AZD7442. Serum was collected prior to AZD7442 administration and at 24 hours and 3, 7, and 14 days later. PK parameters were calculated using noncompartmental methods. Following 600 mg i.m., the geometric mean maximum concentration (C_max) was 38.19 μg/mL (range: 17.30–60.80) and 37.33 μg/mL (range: 14.90–58.90) for tixagevimab and cilgavimab, respectively. Median observed time to maximum concentration (T_max) was 7.1 and 7.0 days for tixagevimab and cilgavimab, respectively. Serum concentrations after i.m. dosing were similar to the i.v. dose (27–29 μg/mL each component) at 3 days. The area under the concentration-time curve (AUC)_0–7d geometric mean ratio was 0.9 for i.m. vs. i.v. Participants with higher weight or body mass index were more likely to have lower concentrations with either route. Women appeared to have higher interparticipant variability in concentrations compared with men. The concentrations of tixagevimab and cilgavimab after administration i.m. to the thigh were similar to those achieved with i.v. after 3 days from dosing. Exposure in the i.m. group was 90% of i.v. over 7 days. Administration to the thigh can be considered to provide consistent mAb exposure and improve access.

中文翻译：

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Tixagevimab/Cilgavimab (AZD7442) 静脉注射与肌肉注射治疗有症状 SARS-CoV-2 感染的药代动力学比较

AZD7442 (Evusheld) 是两种人抗严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 单克隆抗体 (mAb) 的组合，即 tixagevimab (AZD8895) 和 cilgavimab (AZD1061)。给药途径是改善治疗可及性的一个重要考虑因素。我们评估了在有症状的 COVID-19 门诊成人中，大腿肌肉注射 (im) 600 mg 与静脉注射 (iv) 300 mg 后 AZD7442 吸收的药代动力学 (PK)。PK 分析包括 110 名参与者中的 84 名随机接受肌肉注射 AZD7442 和 61 名随机接受静脉注射 AZD7442 的 16 名。在 AZD7442 给药之前以及 24 小时以及 3、7 和 14 天后收集血清。使用非房室方法计算 PK 参数。肌注 600 mg 后，tixagevimab 和 cilgavimab 的几何平均最大浓度 ( Cmax ) 分别为 38.19 μg/mL（范围：17.30-60.80）和 37.33 μg/mL（范围：14.90-58.90）_。tixagevimab 和 cilgavimab达到最大浓度的中位观察时间 ( T _max ) 分别为 7.1 天和 7.0 天。肌内给药后第 3 天的血清浓度与静脉注射剂量相似（每种成分 27-29 μg/mL）。肌注与静脉注射的浓度-时间曲线下面积 (AUC) _0-7d几何平均比率为 0.9 体重或体重指数较高的参与者更有可能通过任一途径获得较低的浓度。与男性相比，女性参与者之间的浓度差异似乎更大。大腿肌肉内给药后，替克维单抗和西加维单抗的浓度与给药 3 天后静脉注射所达到的浓度相似。7 天内，肌肉注射组的暴露量为静脉注射组的 90%。可以考虑对大腿进行给药，以提供一致的单克隆抗体暴露并改善通路。