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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Imipenem in burn patients: pharmacokinetic profile and PK/PD target attainment
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Imipenem in burn patients: pharmacokinetic profile and PK/PD target attainment

机译：亚胺培南在烧伤患者中的药动学特征和PK / PD目标达成

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摘要

Unpredictable pharmacokinetics (PK) in burn patients may result in plasma concentrations below concentrations that are effective against common pathogens. The present study evaluated the imipenem PK profile and pharmacokinetic/pharmacodynamics (PK/PD) correlation in burn patients. Fifty-one burn patients, 38.7 years of age (mean), 68.0 kg, 36.3% total burn surface area (TBSA), of whom 84% (43/51) exhibited thermal injury, 63% inhalation injury and 16% electrical injury (8/51), all of whom were receiving imipenem treatment were investigated. Drug plasma monitoring, PK study (120 sets of plasma levels) and PK/PD correlation were performed in a series of blood samples. Only 250 mu l of plasma samples were required for drug plasma measurements using the ultra filtration technique for the purification of biological matrix and quantification using liquid chromatography. Probability of target attainment (PTA) was calculated using a PD target of 40% free drug concentrations above the minimum inhibitory concentration (40%fT > 4MIC). Significant differences in PK parameters (medians), such as biological half-life (2.2 vs 5.5 h), plasma clearance (16.2 vs 1.4 l h(-1)) and volume of distribution (0.86 vs 0.19 l kg (-1)), were registered in burn patients via comparisons of set periods with normal renal function against periods of renal failure. Correlations between creatinine clearance and total body plasma clearance were also obtained. In addition, the PK profile did not change according to TBSA during sets when renal function was preserved. PTA was 89% for MIC values up to 4mg l (-1). In conclusion, imipenem efficacy for the control of hospital infection on the basis of PK/PD correlation was guaranteed for burn in patients at the recommended dose regimens for normal renal function (31.1 +/- 9.7 mg kg(-1) daily), but the daily dose must be reduced to 17.2 +/- 9.7 mg kg(-1) during renal failure to avoid neurotoxicity.
机译：烧伤患者中不可预测的药代动力学（PK）可能导致血浆浓度低于对常见病原体有效的浓度。本研究评估了烧伤患者亚胺培南的PK分布和药代动力学/药效学（PK / PD）相关性。 51名烧伤患者，平均年龄38.7岁，体重68.0 kg，总烧伤表面积（TBSA）36.3％，其中84％（43/51）表现为热损伤，63％吸入损伤和16％电损伤（ 8/51），他们都接受了亚胺培南治疗。在一系列血液样本中进行了血浆监测，PK研究（120组血浆水平）和PK / PD相关性。使用超滤技术进行生物血浆的纯化和液相色谱定量仅需要250μl血浆样品即可进行药物血浆测量。使用高于最小抑制浓度（40％fT> 4MIC）的40％游离药物浓度的PD靶标，计算出达到靶标（PTA）的概率。 PK参数（中位数）的显着差异，例如生物半衰期（2.2 vs 5.5 h），血浆清除率（16.2 vs 1.4 lh（-1））和分布体积（0.86 vs 0.19 l kg（-1）），通过比较正常肾脏功能的设定时期和肾衰竭时期，对烧伤患者进行登记。肌酐清除率与全身血浆清除率之间也具有相关性。此外，在保留肾功能的一组试验中，PK谱未根据TBSA改变。对于MIC值高达4mg l（-1），PTA为89％。总之，在推荐的正常肾脏功能剂量方案（每天31.1 +/- 9.7 mg kg（-1））下，可确保根据PK / PD相关性使用亚胺培南控制医院感染的疗效，但是肾衰竭期间必须将每日剂量降低至17.2 +/- 9.7 mg kg（-1），以避免神经毒性。

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