Clinical Pharmacokinetics and Pharmacodynamics of Antihyperglycemic Medications in Children and Adolescents with Type 2 Diabetes Mellitus.
Clinical Pharmacokinetics and Pharmacodynamics of Antihyperglycemic Medications in Children and Adolescents with Type 2 Diabetes Mellitus.
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DOI：
10.1007/s40262-016-0472-6
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发表时间：
2017-06
影响因子：
4.5
通讯作者：
Karimani A
中科院分区：
文献类型：
--
作者：
Akhlaghi F;Matson KL;Mohammadpour AH;Kelly M;Karimani A
儿童和青少年2型糖尿病（T2 DM）的发病率一直在上升。这种情况与肥胖有关，在少数民族或女性青年中的流行率较高。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成功;因此，需要药物治疗方法来治疗青年T2 DM。目前，在美国，只有二甲双胍和胰岛素被批准用于治疗儿童T2 DM。在该人群中，还超说明书使用了几种降糖药，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。此外，一些临床试验正在进行中，旨在解决新的降糖药在这一人群中的安全性和有效性。关于儿童或青少年中降糖药的安全性、有效性或药代动力学知之甚少。我们预测这些药物在年轻人中的药代动力学的能力受到阻碍，首先是由于缺乏关于药物代谢酶和转运蛋白在这一人群中的表达和活性的信息，其次是由于肥胖和脂肪肝等其他疾病的发生。这篇手稿综述了儿童和青少年（青年）肥胖和T2 DM的患病率。然后，我们总结了已发表的关于青年降糖药物安全性和有效性的研究。药物分布可能受年龄或青春期的影响，因此将在青年和成人之间比较药物代谢和异生物质转运蛋白的不同途径的表达和活性，然后总结该人群中目前使用的降糖药的药代动力学研究。
The incidence of type 2 diabetes mellitus (T2DM) among children and adolescents has been rising. This condition is associated with obesity, and the prevalence is higher among minority or female youth. Lifestyle modification including diet and exercise is only successful in a small portion of the patients; therefore, pharmacotherapy approaches are needed to treat T2DM among youth. Currently, in the United States, only metformin and insulin are approved for the treatment of T2DM in children. Several antihyperglycemic agents including exenatide, glimepiride, glyburide, liraglutide, pioglitazone and rosiglitazone are also used off-label in this population. Moreover, several clinical trials are ongoing that are aimed to address 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 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 occurrence of additional conditions such as obesity and fatty liver disease. This manuscript reviews the prevalence of obesity and T2DM in children and adolescents (youth). We have then summarized published studies on safety and effectiveness of antihyperglycemic medications in youth. Drug disposition may be affected by age or puberty thus the expression and activity of different pathways for drug metabolism and xenobiotic transporters will be compared between youth and adults followed by summarizing pharmacokinetics studies of antihyperglycemic agents currently used in this population.