Shakhnovich V, Abdel-Rahman S, Friesen C A, Weigel J, Pearce R E, Gaedigk A, Leeder J S, Kearns G L
Department of Pediatrics, University of Missouri Kansas City School of Medicine, Kansas City, MO, USA.
Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation, The Childrens Mercy Hospital, Kansas City, MO, USA.
Pediatr Obes. 2019 Jan;14(1). doi: 10.1111/ijpo.12459. Epub 2018 Sep 26.
Children with obesity are more likely to suffer gastroesophageal reflux disease, requiring acid-suppression therapy with proton pump inhibitors (PPIs) and no guidelines regarding dosing.
To prospectively evaluate lean-body-weight-based (LBW) dosing of the PPI pantoprazole for children with and without obesity.
Methods: Sixty-two children (6-17 years) received a one-time oral dose of liquid pantoprazole (1.2 mg kg LBW). Plasma pantoprazole concentrations were measured at 10 time points over 8 h and pharmacokinetic (PK) profiles generated using non-compartmental techniques, in order to compare PK parameters of interest between children with and without obesity, while accounting for CYP2C19 genotype.
Adjusted for milligram-per-kilogram total body weight (TBW) pantoprazole received, apparent drug clearance (CL/F) was reduced 50% in children with vs. without obesity (p=0.03). LBW-based dosing compensated for this reduction in CL/F (p = 0.15).
To achieve comparable systemic PPI exposures for children with and without obesity, we recommend using LBW, rather than TBW-based dosing for pantoprazole.
肥胖儿童更易患胃食管反流病,需要使用质子泵抑制剂(PPI)进行抑酸治疗,且尚无关于给药剂量的指南。
前瞻性评估基于瘦体重(LBW)的PPI泮托拉唑在肥胖和非肥胖儿童中的给药情况。
62名6至17岁儿童接受了一次口服液体泮托拉唑(1.2毫克/千克LBW)。在8小时内的10个时间点测量血浆泮托拉唑浓度,并使用非房室技术生成药代动力学(PK)曲线,以比较肥胖和非肥胖儿童之间的相关PK参数,同时考虑CYP2C19基因型。
根据每千克体重(TBW)接受的泮托拉唑毫克数进行调整后,肥胖儿童的表观药物清除率(CL/F)比非肥胖儿童降低了50%(p = 0.03)。基于LBW的给药弥补了CL/F的这种降低(p = 0.15)。
为使肥胖和非肥胖儿童获得相当的全身性PPI暴露量,我们建议使用基于LBW而非TBW的泮托拉唑给药方法。