用于因药物依从性差而导致的儿童结节性硬化症患者的西罗莫司延迟或漏服剂量的补救剂量建议。
Remedial Dosing Recommendations for Sirolimus Delayed or Missed Dosages Caused by Poor Medication Compliance in Pediatric Tuberous Sclerosis Complex Patients.
机构信息
Department of Pharmacy, The Affiliated Changzhou Children's Hospital of Nantong University, Changzhou, Jiangsu 213003, China.
Department of Pharmacy, Taixing People's Hospital, Taixing, Jiangsu 225400, China.
出版信息
Curr Pharm Des. 2024;30(11):877-886. doi: 10.2174/0113816128299479240213151714.
BACKGROUND
Delayed or missed dosages caused by poor medication compliance significantly affected the treatment of diseases in children.
AIMS
The present study aimed to investigate the influence of delayed or missed dosages on sirolimus pharmacokinetics (PK) in pediatric tuberous sclerosis complex (TSC) patients and to recommend remedial dosages for nonadherent patients.
METHODS
A published sirolimus population PK model in pediatric TSC patients was used to assess the influence of different nonadherence scenarios and recommend optimally remedial dosages based on Monte Carlo simulation. Thirteen nonadherent scenarios were simulated in this study, including delayed 2h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, 22 h, 23.5 h, and missed one dosage. Remedial dosing strategies contained 10-200% of scheduled dosages. The optimal remedial dosage was that with the maximum probability of returning the individual therapeutic range.
RESULTS
For delayed or missed sirolimus dosages in pediatric TSC patients, when the delayed time was 0-8 h, 8-10 h, 10-18 h, 18-22.7 h, 22.7-24 h, 70%, 60%, 40%, 30%, 20% scheduled dosages were recommended to take immediately. When one dosage was missed, 120% of scheduled dosages were recommended at the next dose.
CONCLUSION
It was the first time to recommend remedial dosages for delayed or missed sirolimus therapy caused by poor medication compliance in pediatric TSC patients based on Monte Carlo simulation. Meanwhile, the present study provided a potential solution for delayed or missed dosages in clinical practice.
背景
因用药依从性差导致的药物剂量延迟或遗漏，显著影响了儿童疾病的治疗效果。
目的
本研究旨在探讨儿童结节性硬化症（TSC）患者药物剂量延迟或遗漏对西罗莫司药代动力学（PK）的影响，并为不依从患者推荐补救剂量。
方法
使用已发表的儿童 TSC 患者西罗莫司群体 PK 模型，评估不同不依从情景对 PK 的影响，并基于蒙特卡罗模拟推荐最优补救剂量。本研究共模拟了 13 种不依从情景，包括延迟 2 h、4 h、6 h、8 h、10 h、12 h、14 h、16 h、18 h、20 h、22 h、23.5 h 和漏服一次剂量。补救给药策略包含了原计划剂量的 10%-200%。最优补救剂量是使个体治疗窗内的概率最大的剂量。
结果
对于儿童 TSC 患者西罗莫司剂量的延迟或遗漏，当延迟时间为 0-8 h、8-10 h、10-18 h、18-22.7 h、22.7-24 h、70%、60%、40%、30%、20%时，建议立即服用原计划剂量的 70%、60%、40%、30%、20%。漏服一次剂量时，建议在下一次剂量时服用原计划剂量的 120%。
结论
这是首次基于蒙特卡罗模拟为儿童 TSC 患者因用药依从性差导致的西罗莫司治疗剂量延迟或遗漏推荐补救剂量。同时，本研究为临床实践中药物剂量的延迟或遗漏提供了潜在的解决方案。
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