MINT, INSERM U1066, CNRS 6021, UNIV Angers, SFR-ICAT 4208, IBS-CHU Angers, 4 rue Larrey, Angers 49933 Cedex 9, France; CHU Angers, 4 rue Larrey, Angers 49933 Cedex 9, France.
MINT, INSERM U1066, CNRS 6021, UNIV Angers, SFR-ICAT 4208, IBS-CHU Angers, 4 rue Larrey, Angers 49933 Cedex 9, France.
Biomed Pharmacother. 2023 Oct;166:115281. doi: 10.1016/j.biopha.2023.115281. Epub 2023 Aug 11.
Obesity is a pathophysiological state defined by a body mass index > 30 kg/m and characterized by an adipose tissue accumulation leading to an important weight increased. Several pathologies named comorbidities such as cardiovascular disease, type 2 diabetes and cancer make obesity the fifth cause of death in the world. Physiological changes impact the four main phases of pharmacokinetics of some drugs and leads to an inappropriate drug-dose. For absorption, the gastrointestinal transit is accelerated, and the gastric empty time is shortened, that can reduce the solubilization and absorption of some oral drugs. The drug distribution is probably the most impacted by the obesity-related changes because the fat mass (FM) increases at the expense of the lean body weight (LBW), leading to an important increase of the volume of distribution for lipophilic drugs and a low or moderately increase of this parameter for hydrophilic drugs. This modification of the distribution may require drug-dose adjustments. By various mechanisms, the metabolism and elimination of drugs are impacted by obesity and should be considered as similar or lower than that non-obese patients. To better understand the necessary drug-dose adjustments in obese patients, a narrative review of the literature was conducted to highlight the main elements to consider in the therapeutic management of adult obese patients.
肥胖是一种病理生理状态，定义为身体质量指数（BMI）>30kg/m2，并以脂肪组织积累导致显著体重增加为特征。一些被称为合并症的病理情况，如心血管疾病、2 型糖尿病和癌症，使肥胖成为世界上第五大致死原因。生理变化影响了某些药物药代动力学的四个主要阶段，导致药物剂量不当。在吸收方面，胃肠道转运加速，胃排空时间缩短，这可能会降低一些口服药物的溶解度和吸收。药物分布可能是受肥胖相关变化影响最大的，因为脂肪质量（FM）的增加以牺牲瘦体重（LBW）为代价，导致亲脂性药物的分布容积显著增加，而亲水性药物的这一参数则较低或适度增加。这种分布的改变可能需要调整药物剂量。由于各种机制，肥胖会影响药物的代谢和消除，应将其视为与非肥胖患者相似或低于非肥胖患者。为了更好地理解肥胖患者所需的药物剂量调整，我们对文献进行了叙述性综述，以强调在治疗肥胖成年患者时需要考虑的主要因素。
