Should patients skip late doses of medication? A pharmacokinetic perspective
Should patients skip late doses of medication? A pharmacokinetic perspective
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DOI：
10.1007/s10928-022-09812-0
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发表时间：
2022-06
影响因子：
2.5
通讯作者：
Elias D. Clark;S. Lawley
中科院分区：
文献类型：
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作者：
Elias D. Clark;S. Lawley
漏服剂量、迟服剂量和其他给药不规则是有效药物治疗的主要障碍，特别是对于慢性疾病的治疗。如果患者没有在规定的时间服用最后一剂药物，应该怎么办？他们是应该晚一点还是跳过？在本文中，我们研究了药物动力学的影响，采取晚剂量。我们考虑了一个单室模型与线性吸收和消除的病人指示采取定期的时间间隔剂量。我们假设患者忘记服用药物，过了一段时间才意识到，必须决定采取什么补救措施。使用数学分析，我们得出了几个指标，量化了晚服用剂量的影响。该度量涉及延迟服用剂量的情况和按时服用剂量的情况下的药物浓度时间过程之间的差异。特别地，度量是在所有时间内的绝对差的积分、差的最大值和在任何单个给药间隔内的差的积分的最大值。我们将这些一般数学公式应用于左旋甲状腺素、阿托伐他汀以及拉莫三嗪的速释和缓释制剂。我们进一步展示了如何将群体变异性立即纳入这些结果。最后，我们使用这种分析，提出处理给药违规行为的一般原则和策略。
Missed doses, late doses, and other dosing irregularities are major barriers to effective pharmacotherapy, especially for the treatment of chronic conditions. What should a patient do if they did not take their last dose at the prescribed time? Should they take it late or skip it? In this paper, we investigate the pharmacokinetic effects of taking a late dose. We consider a single compartment model with linear absorption and elimination for a patient instructed to take doses at regular time intervals. We suppose that the patient forgets to take a dose and then realizes some time later and must decide what remedial steps to take. Using mathematical analysis, we derive several metrics which quantify the effects of taking the dose late. The metrics involve the difference between the drug concentration time courses for the case that the dose is taken late and the case that the dose is taken on time. In particular, the metrics are the integral of the absolute difference over all time, the maximum of the difference, and the maximum of the integral of the difference over any single dosing interval. We apply these general mathematical formulas to levothyroxine, atorvastatin, and immediate release and extended release formulations of lamotrigine. We further show how population variability can be immediately incorporated into these results. Finally, we use this analysis to propose general principles and strategies for dealing with dosing irregularities.