Pharmacokinetics of Metformin in Girls Aged 9 Years
Pharmacokinetics of Metformin in Girls Aged 9 Years
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DOI：
10.2165/11593970-000000000-00000
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发表时间：
2011-01-01
影响因子：
4.5
通讯作者：
Ibanez, Lourdes
中科院分区：
文献类型：
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作者：
Sanchez-Infantes, David;Diaz, Marta;Ibanez, Lourdes
背景与目的：二甲双胍是一种治疗2型糖尿病的双胍类药物。对于出生体重低，青春期早期正常和快速进展的女孩，二甲双胍治疗能够改变这种结果，延长青春期生长，增加身高，推迟月经初潮年龄，改善这些女孩的内分泌代谢状况。在健康成人和2型糖尿病患者中研究了二甲双胍的药代动力学。本研究的目的是研究二甲双胍在年轻、非肥胖女孩中的药代动力学。方法：研究人群包括6名低出生体重和青春期早期正常发作的女孩。研究开始时，这些女孩年龄为9岁，已经接受二甲双胍治疗（850毫克/天，晚餐时间），平均持续时间为8个月。在服用二甲双胍前和服用后12小时采集女孩的血液样本。采用液相色谱-串联质谱法测定血清二甲双胍浓度。计算血清浓度-时间曲线下面积（AUC）、最大血清浓度（C-max）、到达C-max的时间（t(max)）、半衰期（t(1/2)）、分布体积（V-d）和总清除率（CL）。结果：接受类似二甲双胍剂量（21-29 mg/kg）的女孩的二甲双胍浓度-时间曲线相似：在这些女孩中，平均A - UC为21 mg。h/L， C-max为3mg /L， t（max）为2.5 h, t（1/2）为4 h， V-d为111 L， CL为20 L/h。这些值与在成人中观察到的值相当。结论：在9岁女孩中，二甲双胍的药代动力学与成人相当。
Background and Objective: Metformin is a biguanide used in the treatment of type 2 diabetes mellitus. In girls with a low birth weight, and early-normal and rapidly progressive puberty, metformin therapy is capable of modifying this outcome, prolonging pubertal growth, increasing height gain, delaying the age at menarche towards normal and improving the endocrine-metabolic status of these girls. The pharmacokinetics of metformin have been studied in healthy adults and in patients with type 2 diabetes. The objective of this study was to study the pharmacokinetics of metformin in young, non-obese girls.Methods: The study population consisted of six girls with a combined history of low birth weight and early-normal onset of puberty. At the time of the study, these girls were aged 9 years and had been receiving metformin (850 mg/day at dinner time) for a mean duration of 8 months. Blood samples were obtained from the girls before metformin intake and for 12 hours thereafter. Serum metformin concentrations were assessed by liquid chromatography with tandem mass spectrometry. The area under the serum concentration-time curve (AUC), maximum serum concentration (C-max), time to reach the C-max (t(max)), half-life (t(1/2), volume of distribution (V-d) and total clearance (CL) were calculated.Results: Metformin concentration-time curves were similar in girls receiving similar metformin doses (range 21-29 mg/kg): in those girls, the mean A UC was 21 mg . h/L, with a C-max of 3 mg/L, t(max) of 2.5 hours, t(1/2) of 4 hours, V-d of 111 L and CL of 20 L/h. These values are comparable to those observed in adults.Conclusion: In girls aged 9 years, the pharmacokinetics of metformin were comparable to those in adults.