著者

Ryota Tanaka Yosuke Suzuki Yukie Takumi Motoshi Iwao Yuhki Sato Kazuhiko Hashinaga Kazufumi Hiramatsu Jun-ichi Kadota Hiroki Itoh

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.39, no.12, pp.1968-1973, 2016-12-01 (Released:2016-12-01)

参考文献数

28

被引用文献数

12

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Linezolid is an oxazolidinone antibiotic against Gram-positive bacteria. Although thrombocytopenia is a major adverse effect of linezolid, hyponatremia also often develops after linezolid administration. This study examined the frequency of hyponatremia that developed during linezolid treatment and identified its risk factors. In this retrospective, single-center, observational cohort study, 61 hospitalized patients treated with linezolid between January 2013 and January 2015 were analyzed. Hyponatremia was defined as a sodium level of ≤134 mEq/L for the duration of linezolid treatment. Its risk factors were identified via a logistic regression analysis. Hyponatremia occurred in 11 (18.0%) patients, and it was severe in a case (a sodium level of ≤128 mEq/L). Univariate and multiple logistic regression analyses identified the plasma C-reactive protein (CRP) level before the initial administration of linezolid and the concomitant use of a potassium-sparing diuretic as the independent variables associated with the development of hyponatremia. The odds ratios were 1.081 (95% confidence interval [CI]; 1.008–1.158) (p=0.028) and 11.017 (95% CI; 1.869–64.939) (p=0.008), respectively. Before linezolid treatment, the CRP levels of the hyponatremia group were significantly higher than those of the no-hyponatremia group (p<0.001). The frequency of hyponatremia development was significantly higher in the patients who received both the potassium-sparing diuretic and linezolid (p=0.016). These results suggest that the plasma sodium levels of patients with severe inflammation who are treated with linezolid and those of linezolid-treated patients co-administered a potassium-sparing diuretic should be continuously monitored.

著者

Ryota Tanaka Yuhki Sato Koji Goto Norihisa Yasuda Yoshifumi Ohchi Yosuke Suzuki Tamio Ueno Kentaro Ito Tetsuya Kaneko Shusaku Kurogi Ko Nonoshita Hiroki Itoh

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.40, no.8, pp.1226-1231, 2017-08-01 (Released:2017-08-01)

参考文献数

28

被引用文献数

6

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Doripenem (DRPM) is a broad-spectrum antibacterial agent often used as empirical therapy for critically ill patients, although there is a lack of studies validating the recommended dosage regimen for patients admitted to intensive care unit (ICU), based on pharmacokinetic (PK)/pharmacodynamic (PD) index. In this study, we estimated the free time above minimum inhibitory concentration (fT>MIC (%)) of DRPM using population PK analysis of 12 patients in ICU, and evaluated the validity of the dosage regimen stratified by creatinine clearance. Using a 2-compartment population PK model reported previously, the mean total clearance or distribution volume of DRPM estimated by Bayesian estimation was significantly lower or higher than that of based on population PK model. The estimated fT>MIC (%) of the recommended standard (normal renal function: 0.5 g every 8 h, moderate: 0.25 g every 8 h, severe renal impairment: 0.25 g every 12 h) and higher doses (normal: 1.0 g every 8 h, moderate: 0.5 g every 8 h, severe: 0.25 g every 8 h) against MICs of 0.5, 1 and 2 µg/mL exceeded 40% in all patients. When stratified by creatinine clearance, the PK/PD breakpoints estimated by Monte Carlo simulation in three grades of renal function tended to be higher than the previously reported PK/PD breakpoints for patients with urinary tract infection, an infection of lesser severity than ICU patients. These results suggest that the dosage regimen stratified by renal function derived from Japanese package insert may be sufficient to achieve effective treatment in ICU patients.