Impact of Age and Concurrent Antiseizure Medication Use on Lacosamide Dose to Concentration Ratio and Dosing in Pediatric Patients.

Q2 Medicine Journal of Pediatric Pharmacology and Therapeutics Pub Date : 2024-10-01 Epub Date: 2024-10-14 DOI:10.5863/1551-6776-29.5.514

Megan Woods, Stephanie J Phelps, Michael L Christensen, Bernd Meibohm, James W Wheless

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Abstract

Objective: To evaluate age, adjunctive antiseizure medication (ASM), and specific ASMs on lacosamide (LCM) weight normalized dose-to-concentration ratio (DCR) and US Food and Drug Administration (FDA) dosing guidelines in pediatric patients.

Methods: Patients 1 mo to ≤18 years with a LCM serum concentration between October 2009 and June 2017 were considered. Demographics, LCM DCR, and adjunctive ASM were recorded. LCM DCR/hr was used as a surrogate for clearance. Data were stratified by age (1 mo-< 2 yr; ≥ 2-6 yr; ≥ 6-12 yr; and ≥12-≤18 yr), FDA dosing weights, and ASM potential to interaction with LCM.

Results: There were 646 sera (380 patients) with median dose 8.36 mg/kg/day (IQR, 5.92-11.16). 50.2% of doses were within FDA-weight guidelines; however, 40.4% exceeded recommendations. Most (81.3%) LCM concentrations were between 2 and 12 mg/L. A difference existed in DCR between ages, with those <2 years having the highest DCR (p < 0.001). Moving across age groups, the DCR decreases by 30.7%, 50.5%, and 63.4%. There was a weak (r² = 0.073) but significant (p < 0.001) negative correlation between DCR and age. 84.8% received adjunctive ASM consisting of at least one of 31 different ASMs. DCR was higher with adjunctive ASMs compared with monotherapy [0.061 (0.039-0.095) vs 0.043 (0.030-0.062)], respectively (p < 0.001) and was greatest with inducers. Phenobarbital increased DCR by 2.6-fold, topiramate by 72.1%, and clobazam by 32.6%. Inhibitors had no effect.

Conclusions: The correlation between age and DCR was weak, accounting for 6% of variability. Strong inducers significantly increased DCR. Synergy may exist when multiple inducers are given. Weak inhibitors did not affect DCR. Those ≥6 to 11 kg, ≥30 to 50 kg, and those given strong inducers may require larger -initial LCM doses. Serum concentrations should be used to individualize dosing, especially in those receiving strong inducers.

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年龄和同时使用抗癫痫药物对拉科酰胺剂量浓度比和小儿患者剂量的影响

目的评估儿童患者的年龄、辅助抗癫痫药物（ASM）和特定ASM对拉科沙胺（LCM）体重归一化剂量浓度比（DCR）和美国食品药品管理局（FDA）剂量指南的影响：研究对象为 2009 年 10 月至 2017 年 6 月期间拉科酰胺血清浓度为 1 个月至 18 岁的患者。记录人口统计学特征、LCM DCR 和辅助 ASM。LCM DCR/hr 用作清除率的替代指标。数据按年龄（1 mo-＜2 yr；≥2-6 yr；≥6-12 yr；≥12-≤18 yr）、FDA剂量权重和ASM与LCM相互作用的可能性进行了分层：共有 646 份血清（380 名患者），中位剂量为 8.36 毫克/千克/天（IQR，5.92-11.16）。50.2%的剂量符合美国食品药物管理局（FDA）的剂量指南；然而，40.4%的剂量超出了指南建议。大多数（81.3%）LCM 浓度介于 2 至 12 毫克/升之间。不同年龄段的 DCR 存在差异，DCR 与年龄呈显著负相关（p < 0.001），但 2 = 0.073。84.8%的患者接受了由 31 种不同 ASM 中至少一种组成的辅助 ASM。与单药治疗相比，辅助 ASM 的 DCR 更高[分别为 0.061 (0.039-0.095) vs 0.043 (0.030-0.062)] (p < 0.001)，且诱导剂的 DCR 最大。苯巴比妥可使 DCR 增加 2.6 倍，托吡酯增加 72.1%，氯巴扎姆增加 32.6%。抑制剂没有影响：结论：年龄与 DCR 之间的相关性很弱，只占变异性的 6%。强诱导剂可显著提高 DCR。使用多种诱导剂时可能会产生协同作用。弱抑制剂不影响 DCR。体重≥6 至 11 千克、≥30 至 50 千克以及服用强诱导剂的患者可能需要更大的 LCM 初始剂量。血清浓度应用于个体化给药，尤其是接受强诱导剂的患者。

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来源期刊

Journal of Pediatric Pharmacology and Therapeutics Medicine-Pediatrics, Perinatology and Child Health

CiteScore

2.40

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0.00%

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期刊介绍： The Journal of Pediatric Pharmacology and Therapeutics is the official journal of the Pediatric Pharmacy Advocacy Group. JPPT is a peer-reviewed multi disciplinary journal that is devoted to promoting the safe and effective use of medications in infants and children. To this end, the journal publishes practical information for all practitioners who provide care to pediatric patients. Each issue includes review articles, original clinical investigations, case reports, editorials, and other information relevant to pediatric medication therapy. The Journal focuses all work on issues related to the practice of pediatric pharmacology and therapeutics. The scope of content includes pharmacotherapy, extemporaneous compounding, dosing, methods of medication administration, medication error prevention, and legislative issues. The Journal will contain original research, review articles, short subjects, case reports, clinical investigations, editorials, and news from such organizations as the Pediatric Pharmacy Advocacy Group, the FDA, the American Academy of Pediatrics, the American Society of Health-System Pharmacists, and so on.