The effect of nonadherence on phenobarbital concentrations and recommendations on the replacement dose using Monte Carlo simulation.

Q2 Pharmacology, Toxicology and Pharmaceutics

Drug metabolism and personalized therapy Pub Date : 2022-06-17 DOI:10.1515/dmdi-2022-0104

Janthima Methaneethorn

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引用次数: 0

Abstract

Objectives: To determine the impacts of missed phenobarbital (PB) doses on its pharmacokinetics and to investigate the appropriate replacement dosing scheme for various PB missed dose scenarios.

Methods: Monte Carlo simulations were performed using parameters from the selected population pharmacokinetic study. The impacts of missed PB dose and the proper replacement dosing scheme were assessed based on the percent deviation of simulated concentrations outside the reference range from the full adherence scenario.

Results: The impact of missed PB dose on its concentrations depended on the daily dose. The replacement with a respective regular dose and one and a half regular dose was appropriate for the one and two missed doses scenarios for patients receiving PB monotherapy. For patients receiving PB with valproic acid or phenytoin, the same replacement scheme was still appropriate. The results also indicated that weight did not influence the proper replacement dosing scheme.

Conclusions: The impacts of missed PB doses on its pharmacokinetics were identified and the proper replacement dosing schemes for different missed dose scenarios were proposed. These schemes should be implemented based on the clinician's justification of the patient's seizure control.

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使用蒙特卡洛模拟法研究不遵医嘱对苯巴比妥浓度的影响以及对替代剂量的建议。

目的确定苯巴比妥（PB）漏服对其药代动力学的影响，并研究各种苯巴比妥漏服情况下的适当替代剂量方案：使用所选人群药代动力学研究的参数进行蒙特卡罗模拟。方法：使用所选人群药代动力学研究的参数进行蒙特卡洛模拟，根据完全依从情况下模拟浓度超出参考范围的百分比偏差，评估 PB 漏服的影响和适当的替代给药方案：错过 PB 剂量对其浓度的影响取决于每日剂量。对于接受丙戊酸钠单药治疗的患者，在漏服一次和两次的情况下，分别用一次常规剂量和一次半常规剂量替代是合适的。对于接受 PB 与丙戊酸或苯妥英联合治疗的患者，同样的替代方案仍然适用。结果还表明，体重并不影响适当的替代剂量方案：结论：确定了 PB 漏服对其药代动力学的影响，并提出了不同漏服情况下的适当替代剂量方案。这些方案应根据临床医生对患者癫痫发作控制情况的判断来实施。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug metabolism and personalized therapy Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)

CiteScore

2.30

自引率

0.00%

发文量

期刊介绍： Drug Metabolism and Personalized Therapy (DMPT) is a peer-reviewed journal, and is abstracted/indexed in relevant major Abstracting Services. It provides up-to-date research articles, reviews and opinion papers in the wide field of drug metabolism research, covering established, new and potential drugs, environmentally toxic chemicals, the mechanisms by which drugs may interact with each other and with biological systems, and the pharmacological and toxicological consequences of these interactions and drug metabolism and excretion. Topics: drug metabolizing enzymes, pharmacogenetics and pharmacogenomics, biochemical pharmacology, molecular pathology, clinical pharmacology, pharmacokinetics and drug-drug interactions, immunopharmacology, neuropsychopharmacology.