腹膜内注射达托霉素治疗腹膜炎的剂量可能不足：采用蒙特卡洛模拟法优化剂量和疗效。

IF 1.9 4区医学 Q3 INFECTIOUS DISEASES

Journal of Chemotherapy Pub Date : 2024-09-24 DOI:10.1080/1120009X.2024.2407705

Taniya Charoensareerat, Tipvilai Taweepunturat, Vipavee Rodjun, Dhakrit Rungkitwattanakul, Sutthiporn Pattharachayakul, Aroonrut Lucksiri, Chonnikan Chutkrailert, Kittiwan Suksawat, Surisara Phasaprated, Susan J Lewis, Weerachai Chaijamorn

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引用次数: 0

摘要

我们建立了一个两室数学药代动力学模型，对接受 6 小时 4 次换药、每个周期使用 2 升透析液的 CAPD 患者进行一阶消除，以预测达托霉素在治疗 120 小时内的处置情况。药效学目标是血浆 AUC/MIC 等于或大于 666。达到目标概率至少 90% 的剂量被定义为最佳剂量。在接受 CAPD 治疗的患者中，每天腹腔注射 300 毫克，每天换药 1 次，足以治疗 MIC 值为 0.25 毫克/升的金黄色葡萄球菌感染性腹膜炎。对于最低抑菌浓度较高的感染，可能需要更高的剂量。在这种情况下，药效学目标和 MIC 对达托霉素的剂量有重要影响。建议对我们的建议进行临床验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Intraperitoneal daptomycin dosing for peritonitis may be inadequate: a Monte Carlo simulation approach to optimize dosing and outcomes.

A two-compartmental mathematical pharmacokinetic model with first-order elimination of patients receiving CAPD of 4 exchanges for 6 h with 2 L of dialysate used in each cycle was developed to predict daptomycin disposition in 120 h of therapy. The pharmacodynamic target was plasma AUC/MIC equal to or greater than 666. The dose that achieved at least 90% of the probability of target attainment was defined as an optimal dose. Administering intraperitoneal 300 mg daily for 1 exchange daily regimen would be sufficient to treat peritonitis with S. aureus infection with MICs of 0.25 mg/L in patients undergoing CAPD. A higher dosage may be required for infections with a higher minimum inhibitory concentration. Pharmacodynamic targets and MICs significantly contributed to daptomycin doses in this setting. Clinical validation of our recommendations is recommended.

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来源期刊

Journal of Chemotherapy 医学-药学

CiteScore

3.70

自引率

0.00%

发文量

144

审稿时长

6-12 weeks

期刊介绍： The Journal of Chemotherapy is an international multidisciplinary journal committed to the rapid publication of high quality, peer-reviewed, original research on all aspects of antimicrobial and antitumor chemotherapy. The Journal publishes original experimental and clinical research articles, state-of-the-art reviews, brief communications and letters on all aspects of chemotherapy, providing coverage of the pathogenesis, diagnosis, treatment, and control of infection, as well as the use of anticancer and immunomodulating drugs. Specific areas of focus include, but are not limited to: · Antibacterial, antiviral, antifungal, antiparasitic, and antiprotozoal agents; · Anticancer classical and targeted chemotherapeutic agents, biological agents, hormonal drugs, immunomodulatory drugs, cell therapy and gene therapy; · Pharmacokinetic and pharmacodynamic properties of antimicrobial and anticancer agents; · The efficacy, safety and toxicology profiles of antimicrobial and anticancer drugs; · Drug interactions in single or combined applications; · Drug resistance to antimicrobial and anticancer drugs; · Research and development of novel antimicrobial and anticancer drugs, including preclinical, translational and clinical research; · Biomarkers of sensitivity and/or resistance for antimicrobial and anticancer drugs; · Pharmacogenetics and pharmacogenomics; · Precision medicine in infectious disease therapy and in cancer therapy; · Pharmacoeconomics of antimicrobial and anticancer therapies and the implications to patients, health services, and the pharmaceutical industry.