蒙特卡洛模拟厄洛替尼漏服及补服方案评价

目的:根据厄洛替尼群体药动学(PPK)模型,应用蒙特卡洛模拟(MCS)评价肿瘤患者厄洛替尼漏服及补服方案。方法:根据厄洛替尼PPK模型,以口服150 mg qd为给药方案,应用非线性混合效应动力学模型(NONMEM)软件对患者漏服及不同时间段补服方案(6 h,12 h,18 h,24 h双倍剂量补服)进行10 000次MCS,计算漏服及补服方案下个体治疗窗(ITW)外人群比例和ITW外持续时间(>5%人群),评估各场景下补服方案的合理性。结果:患者漏服厄洛替尼时,血药浓度持续下降至下次用药时间,且影响次日的血药浓度,ITW以下持续时间分别为25.1 h和6.6 h;随着补服时间的延长,ITW以下人群比例从6.82%增加到14.55%,持续时间从5.9 h增加到23.6 h;ITW以上人群比例从5.99%增加到10.74%,持续时间从3.7 h增加到9.7 h。结论:根据MCS结果,患者应提高厄洛替尼用药依从性,避免漏服。一旦出现漏服,可考虑尽快补服,但不建议接近下次给药时间时进行补服或加倍剂量补服,以免增加药物不良反应。

Missed and remedial dosage regimens of erlotinib by Monte Carlo simulation

AIM: To evaluate the missed and remedial dosage regimens in cancer patients using erlotinib population pharmacokinetics (PPK) model by Monte Carlo simulation (MCS). METHODS: According to erlotinib PPK model (150 mg po qd), 10 000 MCS were estimated for missed doses and remedial dosage regimens (6 h, 12 h, 18 h, and 24 h double doses) by NONMEM. The proportion of people outside the individual treatment window (ITW) and duration outside the ITW (>5%) under the missed and remedial regimens were calculated, and the rationality of the supplemental regimen in each scenario were analyzed. RESULTS: When missed taking erlotinib, the drug concentration continued to drop to the next medication time and affected the next day's concentration. The durations below the ITW were 25.1 h and 6.6 h, respectively. The proportion of people below ITW increased from 6.82% to 14.55%, and the duration time increased from 5.9 h to 23.6 h; the proportion of people above ITW increased from 5.99% to 10.74%, and the duration time increased from 3.7 h to 9.7 h. CONCLUSION: According to MCS results, patients should improve erlotinib medication compliance and avoid missed doses. In case of missed dose, remedial should be given as soon as possible, but it is not recommended to take remedial or double dosage near the next administration time to avoid increased adverse drug reactions.