Pharmacokinetics of cefmetazole in plasma, peritoneal fluid, peritoneum, and subcutaneous adipose tissue of patients scheduled for lower gastrointestinal surgery: Dosing considerations based on site-specific pharmacodynamic target attainment
Pharmacokinetics of cefmetazole in plasma, peritoneal fluid, peritoneum, and subcutaneous adipose tissue of patients scheduled for lower gastrointestinal surgery: Dosing considerations based on site-specific pharmacodynamic target attainment
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计划进行下消化道手术的患者血浆、腹腔液、腹膜和皮下脂肪组织中头孢美唑的药代动力学：基于部位特异性药效学目标达到的剂量考虑
DOI：
10.1016/j.jiac.2022.12.005
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发表时间：
2023
影响因子：
2.2
通讯作者：
Takahashi Shinya
中科院分区：
文献类型：
--
作者：
Kaiki Yuki;Ohge Hiroki;Ikawa Kazuro;Uegami Shinnosuke;Watadani Yusuke;Shigemoto Norifumi;Hirano Toshinori;Yoshimura Kosuke;Kitagawa Hiroki;Morikawa Norifumi;Takahashi Shinya
头孢美唑（CMZ）作为碳青霉烯类抗生素的替代药物，近年来引起了人们的关注。在这项研究中，我们调查了CMZ的药代动力学（PK）在血浆中，腹腔液，腹膜，皮下脂肪组织，以评估所需的给药方案，以实现药效学（PD）的目标，在target site.MethodsPatients择期下胃肠道手术静脉注射CMZ。在CMZ输注后和手术期间收集血浆、腹膜液、腹膜和皮下脂肪组织样品，并测量CMZ浓度。非房室和房室PK参数进行了估计，并用于评估网站特定的PD目标achievement.ResultsA共38血浆，27腹膜液，36腹膜，38皮下脂肪组织样本收集10例。非房室PK分析显示，腹膜液-血浆、腹膜-血浆和皮下脂肪组织-血浆的平均药物浓度-时间曲线下面积（AUC 0 -3.5 h）比值分别为0.60、0.36和0.11。根据日本手术部位感染（SSI）监测，基于ESBL-E折点的研究中心特定PD目标达成分析（MIC 90 = 8 mg/L）CMZ每3.5 h 2 g可达到理想的杀菌效果，每6 h 2 g可达到腹膜和腹腔液的PD目标治疗腹腔内感染和预防SSI的给药方案。
IntroductionCefmetazole (CMZ) has gained interest as a carbapenem-sparing alternative to the epidemic of extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-E). In this study, we investigated the pharmacokinetics (PK) of CMZ in plasma, peritoneal fluid, peritoneum, and subcutaneous adipose tissue to assess the dosing regimen needed to achieve pharmacodynamic (PD) goals at the target site.MethodsPatients scheduled for elective lower gastrointestinal surgery were intravenously administered CMZ. Plasma, peritoneal fluid, peritoneum, and subcutaneous adipose tissue samples were collected after CMZ infusion and during the surgery, and CMZ concentrations were measured. The non-compartmental and compartmental PK parameters were estimated and used to evaluate site-specific PD target attainment.ResultsA total of 38 plasma, 27 peritoneal fluid, 36 peritoneum, and 38 subcutaneous adipose tissue samples were collected from 10 patients. The non-compartmental PK analysis revealed the ratios of the mean area under the drug concentration-time curve (AUC0–3.5 h) of peritoneal fluid-to-plasma, peritoneum-to-plasma, and subcutaneous adipose tissue-to-plasma were 0.60, 0.36, and 0.11, respectively. The site-specific PD target attainment analyses based on the breakpoints for ESBL-E per the Japanese surgical site infection (SSI) surveillance (MIC90= 8 mg/L) revealed that 2 g CMZ every 3.5 h achieved desired bactericidal effect at all sites and 2 g CMZ every 6 h achieved PD goals at peritoneum and peritoneal fluid.ConclusionThese findings clarify the PK of CMZ in abdominal tissues and could help decide optimal dosing regimens to treat intra-abdominal infection and prophylaxis of SSI.