Scholarlink

Purpose <p>To demonstrate how Model-Informed Precision Dosing (MIPD) enables the transition from empirical discontinuation to precise, safe, and rational treatment resumption, as illustrated by the management of a substantial binimetinib overdose in a frail elderly patient.</p> Methods <p>We present the case of an 80-year-old female (50&#xa0;kg) with BRAF V600R-mutated metastatic melanoma who inadvertently received 135&#xa0;mg of binimetinib twice daily (270&#xa0;mg/day) instead of the recommended 45&#xa0;mg twice daily. In the absence of overdose guidelines, a multidisciplinary workflow integrating pharmacovigilance assessment and model-informed simulations was initiated. A population pharmacokinetic model of binimetinib was used to simulate the patient-specific washout and estimate the optimal timing for therapy resumption at the median steady-state trough concentration (Cmin, ss). A virtual population (<i>n</i> = 10,000) receiving the standard regimen was simulated, excluding the 5th and 95th percentiles to remove aberrant predictions.</p> Results <p>Aside from bilateral subretinal fluid not requiring discontinuation, no acute dose-limiting toxicities were observed. Simulations estimated a target median Cmin, ss of 103.1&#xa0;µg/L (CV 47.8%; range 16.8–230.0&#xa0;µg/L). The patient’s predicted time to return within this exposure target was ~ 37&#xa0;h after the first overdose. Treatment was resumed at 36&#xa0;h, omitting one scheduled dose. Measured binimetinib concentration at resumption was 52&#xa0;µg/L, within the predicted variability range. The patient tolerated reinitiation, ocular findings resolved completely within two weeks.</p> Conclusion <p>This case illustrates that MIPD provides a rational alternative to empirical prolonged discontinuation after medication errors. By quantifying exposure and variability, therapy resumption was optimized in a frail patient with high oncologic risk.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

From empirical caution to precision resumption: model-informed management of a binimetinib overdose in a frail elderly patient

  • 期刊论文

  • 发表日期：

    2026年3月28日

查看全文
  • Hamza Sayadi,
  • Yeleen Fromage,
  • Marc Labriffe,
  • Caroline Monchaud,
  • Héloïse Jourdain,
  • Hélène Géniaux,
  • Jean-Baptiste Woillard

摘要

Purpose

To demonstrate how Model-Informed Precision Dosing (MIPD) enables the transition from empirical discontinuation to precise, safe, and rational treatment resumption, as illustrated by the management of a substantial binimetinib overdose in a frail elderly patient.

Methods

We present the case of an 80-year-old female (50 kg) with BRAF V600R-mutated metastatic melanoma who inadvertently received 135 mg of binimetinib twice daily (270 mg/day) instead of the recommended 45 mg twice daily. In the absence of overdose guidelines, a multidisciplinary workflow integrating pharmacovigilance assessment and model-informed simulations was initiated. A population pharmacokinetic model of binimetinib was used to simulate the patient-specific washout and estimate the optimal timing for therapy resumption at the median steady-state trough concentration (Cmin, ss). A virtual population (n = 10,000) receiving the standard regimen was simulated, excluding the 5th and 95th percentiles to remove aberrant predictions.

Results

Aside from bilateral subretinal fluid not requiring discontinuation, no acute dose-limiting toxicities were observed. Simulations estimated a target median Cmin, ss of 103.1 µg/L (CV 47.8%; range 16.8–230.0 µg/L). The patient’s predicted time to return within this exposure target was ~ 37 h after the first overdose. Treatment was resumed at 36 h, omitting one scheduled dose. Measured binimetinib concentration at resumption was 52 µg/L, within the predicted variability range. The patient tolerated reinitiation, ocular findings resolved completely within two weeks.

Conclusion

This case illustrates that MIPD provides a rational alternative to empirical prolonged discontinuation after medication errors. By quantifying exposure and variability, therapy resumption was optimized in a frail patient with high oncologic risk.