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- Title
Population pharmacokinetics of intravenous daptomycin in critically ill patients: implications for selection of dosage regimens.
- Authors
Jianhua Wu; Xiangyi Zheng; Liu Zhang; Jiajun Wang; Yifei Lv; Yujie Xi; Dongfang Wu
- Abstract
Daptomycin is gaining prominence for the treatment of methicillin-resistant Staphylococcus aureus infections. However, the dosage selection for daptomycin in critically ill patients remains uncertain, especially in Chinese patients. This study aimed to establish the population pharmacokinetics of daptomycin in critically ill patients, optimize clinical administration plans, and recommend appropriate dosage for critically ill patients in China. The study included 64 critically ill patients. Blood samples were collected at the designated times. The blood daptomycin concentration was determined using validated liquid chromatography-tandem mass spectrometry. A nonlinear mixedeffects model was applied for the population pharmacokinetic analysis and Monte Carlo simulations of daptomycin. The results showed a twocompartment population pharmacokinetic model of daptomycin in critically ill adult Han Chinese patients. Monte Carlo simulations revealed that a daily dose of 400 mg of daptomycin was insufficient for the majority of critically ill adult patients to achieve the anti-infective target. For critically ill adult patients with normal renal function (creatinine clearance rate >90 mL/min), the probability of achieving the target only reached 90% when the daily dose was increased to 700 mg. For patients undergoing continuous renal replacement therapy (CRRT), 24 h administration of 500 mg met the pharmacodynamic goals and did not exceed the safety threshold in most patients. Therefore, considering its efficacy and safety, intravenous daptomycin doses are best scaled according to creatinine clearance, and an increased dose is recommended for critically ill patients with hyperrenalism. For patients receiving CRRT, medication is recommended at 24 h intervals.
- Subjects
CHINA; CRITICALLY ill; DAPTOMYCIN; LIQUID chromatography-mass spectrometry; STAPHYLOCOCCUS aureus infections; METHICILLIN-resistant staphylococcus aureus; PHARMACOKINETICS
- Publication
Frontiers in Pharmacology, 2024, p1
- ISSN
1663-9812
- Publication type
Article
- DOI
10.3389/fphar.2024.1378872