Intravenous (i.v.) minocycline is increasingly used to treat infections caused by multidrug-resistant (MDR) Acinetobacter baumannii. Despite its being approved nearly 50 years ago, published information on its pharmacokinetic (PK) profile is limited. This multicenter study examined the PK and probability of pharmacokinetic-pharmacodynamic (PK-PD) target attainment profile of i.v. minocycline in critically ill patients, with suspected or documented infection with Gram-negative bacteria. The PK study population included 55 patients who received a single 200-mg i.v. dose of minocycline. Plasma PK samples were collected predose and 1, 4, 12, 24, 36, and 48 h after initiation of minocycline. Total and unbound minocycline concentrations were determined at each time point. Probabilities of achieving the PK-PD targets associated with stasis and 1-log killing (free area under the curve above the MIC [fAUC:MIC] of 12 and 18, respectively) in an immunocompetent animal pneumonia infection model of A. baumannii were evaluated. A two-compartment population PK model with zero-order i.v. input and first-order elimination, which estimated a constant fraction unbound (f_ub) for minocycline, best characterized the total and unbound plasma minocycline concentration-time data. The only two covariates retained in the final PK model were body surface area (associated with central volume of distribution) and albumin (associated with f_ub). In the PK-PD probability of target attainment analyses, minocycline 200 mg i.v. every 12 h (Q12H) was predicted to result in a suboptimal PK-PD profile for patients with A. baumannii infections with MIC values of >1 mg/liter. Like all PK-PD profiling studies of this nature, these findings need clinical confirmation.

中文翻译：

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在 IV 期开放标签多中心研究 (ACUMIN) 中对危重成人单次输注后注射用米诺环素的药代动力学和药效学分析

静脉内 (iv) 米诺环素越来越多地用于治疗由耐多药 (MDR)鲍曼不动杆菌引起的感染. 尽管它在近 50 年前获得批准，但关于其药代动力学 (PK) 概况的已发表信息是有限的。这项多中心研究检查了在疑似或记录有革兰氏阴性菌感染的危重患者中静脉注射米诺环素的 PK 和药代动力学-药效学 (PK-PD) 目标达到曲线的概率。PK 研究人群包括 55 名接受单次 200 mg iv 剂量米诺环素的患者。在给药前和开始使用米诺环素后 1、4、12、24、36 和 48 小时收集血浆 PK 样品。在每个时间点测定总和未结合的米诺环素浓度。达到与停滞和 1-log 杀灭相关的 PK-PD 目标的概率（MIC 上方曲线下的自由面积 [ fAUC:MIC] 分别为 12 和 18）在鲍曼不动杆菌的免疫活性动物肺炎感染模型中进行了评估。具有零级 iv 输入和一级消除的两室群体 PK 模型估计了米诺环素的恒定未结合分数 (f _ub )，最好地表征了总和未结合的血浆米诺环素浓度-时间数据。在最终 PK 模型中保留的仅有的两个协变量是体表面积（与中心分布容积相关）和白蛋白（与 f _ub相关）。在目标达到分析的 PK-PD 概率中，预计每 12 小时 (Q12H) 静脉注射米诺环素 200 mg 会导致鲍曼不动杆菌患者的 PK-PD 曲线不理想MIC 值 >1 毫克/升的感染。像所有这种性质的 PK-PD 分析研究一样，这些发现需要临床证实。