Matson Kelly L, Horton Evan R, Capino Amanda C
University of Rhode Island College of Pharmacy (KLM), Kingston, RI.
UMass Memorial Health Children's Medical Center (KLM), Worcester, MA.
J Pediatr Pharmacol Ther. 2024 Oct;29(5):550-553. doi: 10.5863/1551-6776-29.5.550. Epub 2024 Oct 14.
Approximately 14.7 million US children aged 2 to 19 years are obese. This creates significant challenges to dosing medications that are primarily weight based (mg/kg) and in predicting pharmacokinetics parameters in pediatric patients. Obese individuals generally have a larger volume of distribution (Vd) for lipophilic medications. Conversely, the Vd of hydrophilic medications may be increased or decreased owing to increased lean body mass, blood volume, and decreased percentage of total body water. They may also experience decreased hepatic clearance secondary to fatty infiltrates of the liver. Hence, obesity may affect loading dose, dosage interval, plasma half-life, and time to reach steady-state concentration for various medications. Weight-based dosing is also a cause for potential medication errors. This position statement of the Pediatric Pharmacy Association recommends that weight-based dosing should be used in patients ages <18 years who weigh <40 kg; weight-based dosing should be used in patients ≥40 kg, unless the recommended adult dose for the specific indication is exceeded; clinicians should use pharmacokinetic analysis for adjusting medications in children diagnosed with overweight and obesity; and research efforts continue to evaluate dosing of medications in children diagnosed with overweight and obesity.
美国约有1470万2至19岁的儿童肥胖。这给主要基于体重(毫克/千克)给药的药物剂量计算以及预测儿科患者的药代动力学参数带来了重大挑战。肥胖个体通常对亲脂性药物具有更大的分布容积(Vd)。相反,亲水性药物的Vd可能会因瘦体重增加、血容量增加以及全身水含量百分比降低而增加或减少。他们还可能因肝脏脂肪浸润而导致肝清除率降低。因此,肥胖可能会影响各种药物的负荷剂量、给药间隔、血浆半衰期以及达到稳态浓度的时间。基于体重的给药也是潜在用药错误的一个原因。儿科药学协会的这份立场声明建议,体重小于40千克的18岁以下患者应采用基于体重的给药方法;体重≥40千克的患者应采用基于体重的给药方法,除非超过了特定适应症的推荐成人剂量;临床医生应对被诊断为超重和肥胖的儿童进行药代动力学分析以调整用药;并且研究工作应继续评估被诊断为超重和肥胖的儿童的药物剂量。