蒙特卡洛模拟埃克替尼漏服及补救方案

Missed and remedial dosage regimens of icotinib by Monte Carlo simulation

目的通过蒙特卡洛模拟(MCS)埃克替尼漏服及相应补救场景,评估各补服方案合理性。方法根据埃克替尼群体药动学模型,以口服125 mg每日3次(6:00、12:00、18:00)为给药方案,应用NONMEM软件对患者单次漏服和连续漏服2次的场景及单次剂量加倍的补救方案进行5 000次模拟。计算不同场景下个体治疗窗(ITW)外人群比例及> 5%人群处于ITW以下的持续时间,分析埃克替尼漏服时加倍剂量补服方案的合理性。结果患者单次漏服的场景中,早晨或晚间漏服对血药浓度波动影响较大,中午漏服影响较小。漏服2次的ITW外人群比例明显高于漏服1次比例。出现漏服后,如补服加倍剂量,ITW以上人群比例增加,持续时间约为2 h。结论根据MCS结果,当服用埃克替尼的患者出现漏服时,不建议于下次用药时服用加倍剂量补救,以免增加用药风险。

AIM To assess the rationality of each remedial dosage regimen by estimating missed and remedial dosage regimens of icotinib by Monte Carlo simulation(MCS). METHODS A total of 5 000 simulations were estimated for single or twice missed doses and remedial dosage regimens according to population pharmacokinetics model of icotinib(125 mg tid, po, 6:00, 12:00, 18:00) using NONMEM software. Percentage out of individual treatment window(ITW) and duration of > 5% population under ITW were calculated for each scenario, and the rationality of double dose of icotinib remedial dosage regimens was analyzed. RESULTS Single missed dose in the morning or evening had a greater impact on concentration, and less impact at noon. The percentage outside the ITW of twice missed doses were all higher than single missed doses. Double doses would increase the percentage over ITW and duration(2 h). CONCLUSION Double dose of icotinib is not recommended at the next dose when missed dose occurred according the result of MCS for increasing medication risk.