Dosing of Continuous Fentanyl Infusions in Obese Children: A Population Pharmacokinetic Analysis.
Dosing of Continuous Fentanyl Infusions in Obese Children: A Population Pharmacokinetic Analysis.
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肥胖儿童中连续芬太尼输注的剂量：种群药代动力学分析。
DOI：
10.1002/jcph.1562
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发表时间：
2020-05
影响因子：
2.9
通讯作者：
Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee
中科院分区：
文献类型：
--
作者：
Maharaj AR;Wu H;Zimmerman KO;Speicher DG;Sullivan JE;Watt K;Al-Uzri A;Payne EH;Erinjeri J;Lin S;Harper B;Melloni C;Hornik CP;Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee
肥胖者和非肥胖者之间芬太尼药代动力学(PK)的差异已有报道；然而，儿童肥胖对芬太尼PK的影响相对未知。我们开发了一个群体药代动力学(PopPK)模型，使用机会性收集的样本，这些样本来自按标准护理接受芬太尼治疗的以肥胖为主的儿童。使用基于概率的方法，我们评估了不同持续输液策略在止痛剂浓度范围(1-3 ng/mL)内提供稳态浓度(Css)的能力。32名儿童的53个样本用于PopPK模型的建立。研究参与者的中位年龄(范围)为13岁(2-19岁)，体重为52公斤(16-164)。大多数儿童(94%)患有肥胖症。根据总体重进行异速测量的两室模型提供了与数据适当的拟合。估计典型清除量为32.5L/小时(按比例计算为70公斤)。固定剂量率输注1微克/公斤/小时与在目标范围内实现CS的概率在49%至58%之间；然而，达到CS>；3 ng/毫升的风险随着体重的增加而增加(16公斤时为15%，164公斤时为43%)。建议的基于模型的输液策略在检查的体重范围内保持了在(58%)和(20%)目标范围内达到CS的一致概率。使用体重和清除量之间的异速生长关系来描述我们这群以肥胖为主的儿童静脉注射芬太尼的PK是合适的。我们提出的基于模型的持续输液策略最大化了不同体重儿童达到目标CS的可能性。
Differences in fentanyl pharmacokinetics (PK) between obese and non-obese adults have previously been reported; however, the impact of childhood obesity on fentanyl PK is relatively unknown. We developed a population pharmacokinetic (PopPK) model using opportunistically-collected samples from a cohort of predominately obese children receiving fentanyl per standard of care. Using a probability-based approach, we evaluated the ability of different continuous infusion strategies for providing steady-state concentrations (Css) within an analgesic concentration range (1–3 ng/mL). Fifty-three samples from 32 children were used for PopPK model development. Median (range) age and body weight of study participants were 13 years (2–19) and 52 kg (16–164), respectively. The majority (94%) of children were obese. A two-compartment model allometrically scaled by total body weight provided an appropriate fit to the data. Estimated typical clearance was 32.5 L/h (scaled to 70 kg). A fixed dose rate infusion of 1 mcg/kg/h was associated with probabilities between 49% and 58% for achieving Css within target; however, the risk of achieving Css >3 ng/mL increased with increasing body weight (15% at 16 kg vs. 43% at 164 kg). A proposed model-based infusion strategy maintained consistent probabilities across the examined weight range for achieving Css within (58%) and above (20%) target. Use of an allometric relationship between weight and clearance was appropriate for describing the PK of intravenous fentanyl in our cohort of predominately obese children. Our proposed model-derived continuous infusion strategy maximized the probability of achieving target Css in children of varying weights.
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