Abstract：
BACKGROUND: Delayed or missed doses are inevitable in epilepsy pharmacotherapy. The current remedial measures recommended by the United States Food and Drug Administration (FDA) for non-adherence are generic and lack clinical evidence.
OBJECTIVE: To assess remedial strategies for delayed or missed pregabalin doses in patients with epilepsy using Monte Carlo simulations.
METHODS: Monte Carlo simulations were performed using a published population pharmacokinetic model for pregabalin. The applicability of five proposed remedial regimens as well as FDA recommendations was evaluated by simulating various poor adherence scenarios in eight populations, including those with renal dysfunction.
RESULTS: All proposed remedial strategies were associated with delay duration and renal function. When delays are relatively short, an immediate regular dose is advised. The cut-off time points for taking the regular dose as a remedial regimen were 1, 2, 4, and 12 h for patients with mild renal impairment and normal renal function, moderate renal impairment, severe renal impairment, and end-stage renal disease, respectively. However, when delay aligns closely with a dosing interval, a regular dose combined with a partial dose proves effective. Generally, supplementing 1.3-fold the regular dose at the next scheduled time adequately compensates for the missed dose.
CONCLUSIONS: Model-based simulations provided quantitative evidence for the effectiveness and feasibility of remedial strategies for missed or delayed pregabalin doses.
OBJECTIVE: To assess remedial strategies for delayed or missed pregabalin doses in patients with epilepsy using Monte Carlo simulations.
METHODS: Monte Carlo simulations were performed using a published population pharmacokinetic model for pregabalin. The applicability of five proposed remedial regimens as well as FDA recommendations was evaluated by simulating various poor adherence scenarios in eight populations, including those with renal dysfunction.
RESULTS: All proposed remedial strategies were associated with delay duration and renal function. When delays are relatively short, an immediate regular dose is advised. The cut-off time points for taking the regular dose as a remedial regimen were 1, 2, 4, and 12 h for patients with mild renal impairment and normal renal function, moderate renal impairment, severe renal impairment, and end-stage renal disease, respectively. However, when delay aligns closely with a dosing interval, a regular dose combined with a partial dose proves effective. Generally, supplementing 1.3-fold the regular dose at the next scheduled time adequately compensates for the missed dose.
CONCLUSIONS: Model-based simulations provided quantitative evidence for the effectiveness and feasibility of remedial strategies for missed or delayed pregabalin doses.
摘要：
背景：在癫痫药物治疗中，延迟或错过剂量是不可避免的。美国食品和药物管理局（FDA）针对不依从性建议的当前补救措施是通用的，缺乏临床证据。
目的：使用蒙特卡洛模拟评估癫痫患者延迟或错过普瑞巴林剂量的治疗策略。
方法：使用已发表的普瑞巴林群体药代动力学模型进行蒙特卡罗模拟。通过模拟八个人群的各种不良依从性情况，评估了五个拟议的治疗方案以及FDA建议的适用性。包括肾功能不全的患者.
结果：所有建议的治疗策略均与延迟持续时间和肾功能相关。当延迟相对较短时，建议立即定期剂量。对于轻度肾功能损害和肾功能正常的患者，采取常规剂量作为治疗方案的截止时间点为1、2、4和12h，中度肾功能损害,严重肾功能损害，和终末期肾病，分别。然而,当延迟与给药间隔密切相关时，常规剂量与部分剂量相结合证明是有效的。一般来说,在下一个预定时间补充1.3倍的常规剂量可以充分补偿错过的剂量.
结论：基于模型的模拟为普瑞巴林剂量缺失或延迟的治疗策略的有效性和可行性提供了定量证据。
目的：使用蒙特卡洛模拟评估癫痫患者延迟或错过普瑞巴林剂量的治疗策略。
方法：使用已发表的普瑞巴林群体药代动力学模型进行蒙特卡罗模拟。通过模拟八个人群的各种不良依从性情况，评估了五个拟议的治疗方案以及FDA建议的适用性。包括肾功能不全的患者.
结果：所有建议的治疗策略均与延迟持续时间和肾功能相关。当延迟相对较短时，建议立即定期剂量。对于轻度肾功能损害和肾功能正常的患者，采取常规剂量作为治疗方案的截止时间点为1、2、4和12h，中度肾功能损害,严重肾功能损害，和终末期肾病，分别。然而,当延迟与给药间隔密切相关时，常规剂量与部分剂量相结合证明是有效的。一般来说,在下一个预定时间补充1.3倍的常规剂量可以充分补偿错过的剂量.
结论：基于模型的模拟为普瑞巴林剂量缺失或延迟的治疗策略的有效性和可行性提供了定量证据。
