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腹膜透析相关性腹膜炎患者腹腔内注射万古霉素:群体药代动力学及给药意义

Intraperitoneally Administered Vancomycin in Patients with Peritoneal Dialysis-Associated Peritonitis: Population Pharmacokinetics and Dosing Implications.

作者信息

Hartinger Jan Miroslav, Michaličková Danica, Dvořáčková Eliška, Hronová Karolína, Krekels Elke H J, Szonowská Barbora, Bednářová Vladimíra, Benáková Hana, Kroneislová Gabriela, Závora Jan, Tesař Vladimír, Slanař Ondřej

机构信息

Department of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic.

Division of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University, 2311 EZ Leiden, The Netherlands.

出版信息

Pharmaceutics. 2023 May 2;15(5):1394. doi: 10.3390/pharmaceutics15051394.

Abstract

Peritonitis is a limiting complication of peritoneal dialysis, which is treated by intraperitoneal administration of antibiotics. Various dosing strategies are recommended for intraperitoneally administered vancomycin, which leads to large differences in intraperitoneal vancomycin exposure. Based on data from therapeutic drug monitoring, we developed the first-ever population pharmacokinetic model for intraperitoneally administered vancomycin to evaluate intraperitoneal and plasma exposure after dosing schedules recommended by the International Society for Peritoneal Dialysis. According to our model, currently recommended dosing schedules lead to possible underdosing of a large proportion of patients. To prevent this, we suggest avoiding intermittent intraperitoneal vancomycin administration, and for the continuous dosing regimen, we suggest a loading dose of 20 mg/kg followed by maintenance doses of 50 mg/L in each dwell to improve the intraperitoneal exposure. Vancomycin plasma level measurement on the fifth day of treatment with subsequent dose adjustment would prevent it from reaching toxic levels in the few patients who are susceptible to overdose.

摘要

腹膜炎是腹膜透析的一种限制性并发症,通过腹腔内给予抗生素进行治疗。对于腹腔内给药的万古霉素推荐了多种给药策略,这导致腹腔内万古霉素的暴露量存在很大差异。基于治疗药物监测的数据,我们开发了首个腹腔内给药万古霉素的群体药代动力学模型,以评估按照国际腹膜透析学会推荐的给药方案给药后腹腔内和血浆中的暴露情况。根据我们的模型,目前推荐的给药方案可能导致很大一部分患者用药不足。为防止这种情况,我们建议避免间歇性腹腔内给予万古霉素,对于持续给药方案,我们建议负荷剂量为20mg/kg,随后在每次留腹时给予维持剂量50mg/L,以改善腹腔内暴露情况。在治疗的第五天测量万古霉素血浆水平并随后调整剂量,可防止少数易发生药物过量的患者体内药物达到毒性水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2de/10222948/6073032f69dc/pharmaceutics-15-01394-g001.jpg

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