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肥胖患者的阿哌沙班血浆浓度。

Apixaban plasma concentrations in patients with obesity.

机构信息

Department of Medicine Solna, Karolinska Institutet & Clinical Pharmacology, Karolinska University Hospital Solna, 17176, Stockholm, Sweden.

Department of Clinical Sciences, Karolinska Institutet & Division of Cardiovascular Medicine, Danderyd Hospital, Stockholm, Sweden.

出版信息

Eur J Clin Pharmacol. 2024 Sep;80(9):1343-1354. doi: 10.1007/s00228-024-03696-4. Epub 2024 Jun 1.

Abstract

PURPOSE

Routine therapeutic drug monitoring of apixaban is currently not recommended but may however be warranted in some situations and for some patient groups to provide better and safer treatment. Due to limited data on apixaban concentrations in different subpopulations, it is still unclear which group of patients could possibly gain from monitoring. The purpose of this study was to examine apixaban exposure in patients with obesity compared with normal-weight patients.

METHODS

Forty patients with obesity (mean BMI 39.4 kg/m) and 40 controls with normal weight (mean BMI 23.4 kg/m), treated with apixaban 5 mg twice daily were included. The patients were matched for age, sex, and renal function. Trough and peak apixaban concentrations were measured with LC‒MS/MS methodology.

RESULTS

The median trough concentrations in patients with obesity (58.7, range 10.7-200.7 ng/ml) were slightly higher than those in patients with normal weight (52.0, range 31.0-150.9 ng/ml) (p < 0.05). Notably, the variability in trough concentration was considerably higher in patients with obesity. Peak concentrations were similar in both groups, with a median of 124.5 ng/ml (range 82.0-277.5) and 113.5 ng/ml (range 75.5-334.6) in patients with obesity and normal weight, respectively.

CONCLUSION

Apixaban exposure did not vary substantially between obese and normal weight matched controls, implying that general dose adjustments are not required. However, vast interindividual variability was observed in patients with obesity, suggesting that measuring the concentrations could be valuable for specific patients. Further research is needed to identify which specific patients may benefit from this approach.

摘要

目的

目前不建议常规监测阿哌沙班的治疗药物浓度,但在某些情况下和某些患者群体中,监测可能是合理的,以提供更好和更安全的治疗。由于在不同亚人群中阿哌沙班浓度的相关数据有限,因此仍不清楚哪些患者群体可能从监测中获益。本研究旨在比较肥胖患者与体重正常患者的阿哌沙班暴露情况。

方法

共纳入 40 例肥胖患者(平均 BMI 39.4kg/m²)和 40 例体重正常患者(平均 BMI 23.4kg/m²),两组患者均接受阿哌沙班 5mg 每日两次治疗。患者按年龄、性别和肾功能匹配。采用 LC-MS/MS 法测定阿哌沙班的谷浓度和峰浓度。

结果

肥胖患者的谷浓度中位数(58.7ng/ml,范围 10.7-200.7ng/ml)略高于体重正常患者(52.0ng/ml,范围 31.0-150.9ng/ml)(p<0.05)。值得注意的是,肥胖患者的谷浓度变异性明显更高。两组患者的峰浓度相似,肥胖患者的峰浓度中位数为 124.5ng/ml(范围 82.0-277.5),体重正常患者的峰浓度中位数为 113.5ng/ml(范围 75.5-334.6)。

结论

肥胖和体重正常匹配的对照组之间,阿哌沙班的暴露情况没有明显差异,这意味着一般不需要调整剂量。然而,肥胖患者的个体间变异性很大,这表明测量浓度可能对特定患者有价值。需要进一步研究以确定哪些特定患者可能受益于这种方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/518f/11303434/4cb484b60c5c/228_2024_3696_Fig1_HTML.jpg

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