Andersson T, Hassall E, Lundborg P, Shepherd R, Radke M, Marcon M, Dalväg A, Martin S, Behrens R, Koletzko S, Becker M, Drouin E, Göthberg G
AstraZeneca LP, Wayne, PA 19087-5677, USA.
Am J Gastroenterol. 2000 Nov;95(11):3101-6. doi: 10.1111/j.1572-0241.2000.03256.x.
The aim of this study was to examine the pharmacokinetics of orally administered omeprazole in children.
Plasma concentrations of omeprazole were measured at steady state over a 6-h period after administration of the drug. Patients were a subset of those in a multicenter study to determine the dose, safety, efficacy, and tolerability of omeprazole in the treatment of erosive reflux esophagitis in children. Children were 1-16 yr of age, with erosive esophagitis and pathological acid reflux on 24 h-intraesophageal pH study. The "healing dose" of omeprazole was that at which subsequent intraesophageal pH study normalized. Children remained on this dose for 3 months, and during this period the pharmacokinetics were measured.
A total of 57 children were enrolled in the overall healing phase of the study. Pharmacokinetic study was optional for subjects and was performed in 25 of the 57 enrolled. The doses of omeprazole required were substantially higher doses per kilogram of body weight than in adults. Values of the pharmacokinetic parameters of omeprazole were generally within the ranges previously reported in adults. However, the plasma levels, area under the plasma concentration versus time curve (AUC), plasma half-life (t(1/2)), and maximal plasma concentration (Cmax), were lower in the younger age group, when the AUC and Cmax were normalized to a dose of 1 mg/kg. Furthermore, within the group as a whole, these values showed a gradation from lowest in the children 1-6 yr of age to higher in the older age groups.
The pharmacokinetics of omeprazole in children showed a trend toward higher metabolic capacity with decreasing age, being highest at 1-6 yr of age. This may explain the need for higher doses of omeprazole on a per kilogram basis, not only in children overall compared with adults but, in many cases, particularly in younger children.
本研究旨在探讨口服奥美拉唑在儿童体内的药代动力学。
在给药后6小时的稳态期间测量奥美拉唑的血浆浓度。患者是一项多中心研究中的一部分，该研究旨在确定奥美拉唑治疗儿童糜烂性反流性食管炎的剂量、安全性、疗效和耐受性。儿童年龄为1至16岁，患有糜烂性食管炎且24小时食管内pH值研究显示有病理性酸反流。奥美拉唑的“愈合剂量”是指随后食管内pH值研究恢复正常时的剂量。儿童维持该剂量3个月，在此期间测量药代动力学。
共有57名儿童进入研究的总体愈合阶段。药代动力学研究对受试者为可选项目，在57名入组儿童中有25名进行了该研究。每千克体重所需的奥美拉唑剂量比成人高得多。奥美拉唑药代动力学参数的值一般在先前报道的成人范围内。然而，当将AUC和Cmax标准化为1mg/kg剂量时，较年轻年龄组的血浆水平、血浆浓度-时间曲线下面积（AUC）、血浆半衰期（t(1/2)）和最大血浆浓度（Cmax）较低。此外，在整个组内，这些值呈现出从1至6岁儿童中最低到年龄较大组中较高的梯度变化。
奥美拉唑在儿童体内的药代动力学显示随着年龄降低代谢能力有升高趋势，在1至6岁时最高。这可能解释了不仅与成人相比儿童总体上，而且在许多情况下尤其是较年幼儿童，每千克体重需要更高剂量奥美拉唑的原因。
