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肥胖成年人的万古霉素清除率不能预测肥胖青少年的清除率。

Vancomycin Clearance in Obese Adults is not Predictive of Clearance in Obese Adolescents.

机构信息

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

Department of Clinical Pharmacy, Antonius Hospital, Sneek, The Netherlands.

出版信息

Clin Pharmacokinet. 2023 May;62(5):749-759. doi: 10.1007/s40262-023-01227-5. Epub 2023 Apr 5.

Abstract

BACKGROUND AND OBJECTIVE

Contradictory pharmacokinetic (PK) results have been observed between obese adults and obese adolescents, with absolute clearance (CL) reported to be either unaltered, lower, or higher in obese adolescents compared to obese adults. This study investigates the PK of vancomycin in adolescents and adults who are overweight or obese.

METHODS

Data from 125 overweight and obese adolescents (aged 10-18 years, weight 28.3-188 kg) and 81 overweight and obese adults (aged 29-88 years, weight 66.7-143 kg) were analysed using population PK modelling. In addition to age, sex, renal function estimates, and regular weight descriptors, we evaluated standard weight (WT, defined as weight for length, age, and sex in adolescents and weight for length in adults) and excess weight (WT, defined as total body weight (TBW) minus WT) as covariates in order to distinguish between weight resulting from length versus weight resulting from obesity.

RESULTS

Analyzing adolescents and adults together, vancomycin CL was found to increase with TBW and decrease with increasing age (p < 0.001). A covariate analysis investigating adolescents and adults separately found that vancomycin CL increased with WT in adolescents and adults, albeit with different functions, with adolescents having a higher CL per WT than adults. Moreover, in this separate model, adolescent males had 21% higher CL than adolescent females of the same WT, while in adults, CL decreased with increasing age (p < 0.001).

CONCLUSION

There are apparent differences in vancomycin CL in overweight and obese adults versus overweight and obese adolescents, implying that dosing of vancomycin cannot be directly extrapolated between these populations.

摘要

背景与目的

肥胖成年人和肥胖青少年的药代动力学(PK)结果存在矛盾,与肥胖成年人相比,肥胖青少年的绝对清除率(CL)报告显示未改变、降低或升高。本研究旨在研究超重或肥胖的青少年和成年人中万古霉素的 PK。

方法

使用群体 PK 模型分析了 125 名超重和肥胖青少年(年龄 10-18 岁,体重 28.3-188 公斤)和 81 名超重和肥胖成年人(年龄 29-88 岁,体重 66.7-143 公斤)的数据。除了年龄、性别、肾功能估计值和常规体重描述符外,我们还评估了标准体重(WT,定义为青少年的身高、年龄和性别对应的体重和成年人的身高对应的体重)和超重(WT,定义为总体重(TBW)减去 WT)作为协变量,以区分由长度引起的体重与由肥胖引起的体重。

结果

综合分析青少年和成年人,发现万古霉素 CL 随 TBW 增加而增加,随年龄增加而降低(p < 0.001)。分别对青少年和成年人进行协变量分析发现,万古霉素 CL 在青少年和成年人中随 WT 增加而增加,尽管函数不同,青少年每 WT 的 CL 高于成年人。此外,在这个单独的模型中,青少年男性的 CL 比同 WT 的女性高 21%,而在成年人中,CL 随年龄增加而降低(p < 0.001)。

结论

超重和肥胖的成年人与超重和肥胖的青少年之间,万古霉素 CL 存在明显差异,这意味着不能直接将万古霉素的剂量从这些人群中推断出来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2de/10182161/a79d9f128485/40262_2023_1227_Fig1_HTML.jpg

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