Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.
Clin Pharmacol Ther. 2021 Apr;109(4):942-951. doi: 10.1002/cpt.2181. Epub 2021 Feb 28.
Obesity and its related comorbidities can negatively influence the outcomes of certain infectious diseases. Specific dosing recommendations are often lacking in the product label for patients with obesity that leads to unclear guidance in practice. Higher rates of therapeutic failure have been reported with some fixed dose antibiotics and pragmatic approaches to dose modification are limited for orally administered agents. For i.v. antimicrobials dosed on weight, alternate body size descriptors (ABSDs) have been used to reduce the risk of overdosing. These ABSDs are mathematical transformations of height and weight that represent fat-free weight and follow the same principles as body surface area (BSA)-based dosing of cancer chemotherapy. However, ABSDs are rarely studied in pivotal phase III studies and so can risk the underdosing of antimicrobials in patients with obesity when incorrectly applied in the real-world setting. Specific case examples are presented to highlight these risks. Although general principles may be considered by clinicians, a universal approach to dose modification in obesity is unlikely. Studies that can better distinguish human body phenotypes may help reduce our reliance on height and weight to define dosing. Simple and complex technologies exist to quantify individual body composition that could improve upon our current approach. Early evidence suggests that body composition parameters repurposed from medical imaging data may improve upon height and weight as covariates of drug clearance and distribution. Clinical trials that can integrate human body phenotyping may help us identify new approaches to optimal dose selection of antimicrobials in patients with obesity.
肥胖及其相关的合并症可能会对某些传染病的结果产生负面影响。对于肥胖患者，产品标签中通常缺乏特定的剂量建议，导致实践中指导不明确。一些固定剂量抗生素的治疗失败率较高，而口服药物的剂量调整方法则受到限制。对于按体重给药的静脉内抗菌药物，已经使用了替代身体大小描述符（ABSD）来降低过度给药的风险。这些 ABSD 是身高和体重的数学变换，代表去脂体重，并遵循与基于体表面积（BSA）的癌症化疗剂量相同的原则。然而，ABSD 在关键性 III 期研究中很少被研究，因此在实际应用中，如果不正确应用，可能会导致肥胖患者的抗菌药物剂量不足。本文提供了具体的案例示例来突出这些风险。尽管临床医生可能会考虑一般原则，但不太可能对肥胖患者的剂量调整采用通用方法。可以更好地区分人体表型的研究可能有助于减少我们对身高和体重来定义剂量的依赖。现有的定量个体身体成分的简单和复杂技术可能会改进我们目前的方法。早期证据表明，重新用于医学成像数据的身体成分参数可能会改善身高和体重作为药物清除率和分布的协变量。可以整合人体表型的临床试验可能有助于我们确定肥胖患者抗菌药物最佳剂量选择的新方法。
