Akhlaghi Fatemeh, Matson Kelly L, Mohammadpour Amir Hooshang, Kelly Meghan, Karimani Asieh
Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Office 495 A, 7 Greenhouse Road, Kingston, RI, 02881, USA.
Department of Pharmacy Practice, University of Rhode Island, Kingston, RI, USA.
Clin Pharmacokinet. 2017 Jun;56(6):561-571. doi: 10.1007/s40262-016-0472-6.
The incidence of type 2 diabetes mellitus (T2DM) among children and adolescents has been rising. This condition is associated with obesity, and it's prevalence is higher among minority or female youth. Lifestyle modification including diet and exercise is only successful in a small proportion of patients; therefore, pharmacotherapy approaches are needed to treat T2DM among youth. Currently, in the USA, only metformin and insulin are approved for the treatment of T2DM in children. However, several antihyperglycemic agents including exenatide, glimepiride, glyburide, liraglutide, pioglitazone, and rosiglitazone are also used off-label in this population. Moreover, a number of clinical trials are ongoing that are aimed at addressing the safety and efficacy of newer antihyperglycemic agents in this population. Little is known about the safety, efficacy, or pharmacokinetics of antihyperglycemic agents in children or adolescents. Our ability to predict the pharmacokinetics of these agents in youth is hampered first by the lack of information about the expression and activity of drug-metabolizing enzymes and transporters in this population and second by the presence of comorbid conditions such as obesity and fatty liver disease. This article reviews the prevalence of obesity and T2DM in children and adolescents (youth). We then summarize published studies on safety and effectiveness of antihyperglycemic medications in youth. Drug disposition may be affected by age or puberty and thus the expression and activity of different pathways for drug metabolism and xenobiotic transporters are compared between youth and adults followed by a summary of pharmacokinetics studies of antihyperglycemic agents currently used in this population.
儿童和青少年2型糖尿病（T2DM）的发病率一直在上升。这种疾病与肥胖有关，在少数族裔或青年女性中的患病率更高。包括饮食和运动在内的生活方式改变仅在一小部分患者中取得成功；因此，需要药物治疗方法来治疗青少年T2DM。目前，在美国，只有二甲双胍和胰岛素被批准用于治疗儿童T2DM。然而，包括艾塞那肽、格列美脲、格列本脲、利拉鲁肽、吡格列酮和罗格列酮在内的几种降糖药也在该人群中被超说明书使用。此外，一些旨在研究新型降糖药在该人群中的安全性和有效性的临床试验正在进行。关于降糖药在儿童或青少年中的安全性、有效性或药代动力学知之甚少。我们预测这些药物在青少年中药代动力学的能力首先受到该人群中药物代谢酶和转运体的表达及活性信息缺乏的阻碍，其次受到肥胖和脂肪肝疾病等合并症的影响。本文综述了儿童和青少年（青年）肥胖和T2DM的患病率。然后，我们总结了已发表的关于降糖药物在青年中的安全性和有效性的研究。药物处置可能受年龄或青春期影响，因此比较了青年和成年人之间药物代谢和外源性物质转运不同途径的表达及活性，随后总结了目前该人群中使用的降糖药的药代动力学研究。
