Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan; Department of Pharmacy, Shinshu University Hospital, Matsumoto, Nagano, Japan.
J Infect Chemother. 2023 Feb;29(2):119-125. doi: 10.1016/j.jiac.2022.10.002. Epub 2022 Oct 7.
Plasma daptomycin has not been fully characterized in diabetic and obese patients. This study aimed to evaluate the associations of plasma daptomycin with glycation of serum albumin and obesity.
Infectious patients (n = 70) receiving intravenous daptomycin were enrolled. The plasma concentration of total and free daptomycin were determined using liquid chromatograph-tandem mass spectrometer. The associations of the plasma concentrations of daptomycin with clinical factors including serum albumin fractionations and physical status (obese including overweight, body mass index ≥ 25.0) were investigated. Daptomycin doses were adjusted using total body-weight.
The serum albumin level was positively and negatively correlated with the plasma concentration of total daptomycin and its free fraction proportion, respectively. The serum non-glycated albumin was negatively correlated with the free fraction proportion. The dose-normalized plasma concentration of total daptomycin was higher in the obese patients than in non-obese patients when the body-weight was corrected with total and adjusted values. For the dose adjustment with lean body-weight, no difference was observed in the dose-normalized plasma concentration of total daptomycin between the physical statuses. For each body-weight correction method, physical status did not affect the dose-normalized plasma concentration of free daptomycin.
The glycation of serum albumin and obesity did not associate with dose-normalized plasma free daptomycin. In obese patients, daptomycin dosage adjustment with total body-weight and adjusted body-weight may lead to an apparent excessive exposure resulting in overdosage compared to lean body-weight.
尚未充分研究糖尿病和肥胖患者的血浆达托霉素。本研究旨在评估血浆达托霉素与血清白蛋白糖化和肥胖的关系。
纳入接受静脉滴注达托霉素的感染患者(n=70)。采用液相色谱-串联质谱法测定总达托霉素和游离达托霉素的血浆浓度。研究了达托霉素的血浆浓度与临床因素(包括血清白蛋白分级和身体状况[肥胖包括超重,体重指数≥25.0])的关系。使用总体重调整达托霉素剂量。
血清白蛋白水平与总达托霉素和游离部分比例的血浆浓度呈正相关和负相关。非糖化血清白蛋白与游离部分比例呈负相关。当用总体重和调整体重校正体重时,肥胖患者的总达托霉素剂量标准化血浆浓度高于非肥胖患者。对于用去脂体重进行剂量调整,两种身体状况下的总达托霉素剂量标准化血浆浓度无差异。对于每种体重校正方法,身体状况均不影响游离达托霉素的剂量标准化血浆浓度。
血清白蛋白糖化和肥胖与剂量标准化的游离达托霉素血浆浓度无关。在肥胖患者中,用总体重和调整体重进行达托霉素剂量调整可能会导致明显的暴露过度,与去脂体重相比,导致剂量过大。