Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.
Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China.
Int J Clin Pract. 2022 Aug 23;2022:2786914. doi: 10.1155/2022/2786914. eCollection 2022.
Children admitted to intensive care units (ICUs) often require multiple medications due to the complexity and severity of their disease, which put them at an increased risk for drug interactions. This study examined cytochrome P450-mediated drug-drug interactions (DDIs) based on the Pediatric Intensive Care (PIC) database, with the aim of analyzing the incidence of clinically significant potential drug-drug interactions (pDDIs) and exploring the occurrence of actual adverse reactions.
The Lexicomp database was used to screen cytochrome P450-mediated DDI pairings with good levels of reliability and clear clinical phenotypes. Patients exposed to the above drug pairs during the same period were screened in the PIC database. The incidence of clinically significant pDDIs was calculated, and the occurrence of adverse reactions was explored based on laboratory measurements.
In total, 84 (1.21%) of 6920 children who used two or more drugs were exposed to at least one clinically significant pDDI. All pDDIs were based on CYP3A4, with nifedipine + voriconazole (39.60%) being the most common drug pair, and the most frequent being the J02 class of drugs. Based on laboratory measurements, 15 adverse reactions were identified in 12 patients.
Clinically significant cytochrome P450-mediated pDDIs existed in the children admitted to ICUs, and some of the pDDIs led to adverse clinical outcomes. The use of clinical decision support systems can guide clinical medication use, and clinical monitoring of patients' needs has to be enhanced.
入住重症监护病房（ICU）的儿童常因疾病的复杂性和严重性需要使用多种药物，这使他们面临更高的药物相互作用风险。本研究基于儿科重症监护（PIC）数据库，考察细胞色素 P450 介导的药物-药物相互作用（DDI），旨在分析临床上显著的潜在药物-药物相互作用（pDDI）的发生率，并探讨实际不良反应的发生情况。
使用 Lexicomp 数据库筛选细胞色素 P450 介导的 DDI 对，这些对具有良好的可靠性和明确的临床表型。在 PIC 数据库中筛选同期暴露于上述药物对的患者。计算临床上显著的 pDDI 的发生率，并根据实验室测量结果探索不良反应的发生情况。
共 6920 例使用两种或两种以上药物的儿童中，有 84 例（1.21%）至少发生了一种临床上显著的 pDDI。所有 pDDI 均基于 CYP3A4，硝苯地平+伏立康唑（39.60%）是最常见的药物对，最常涉及的药物类别为 J02 类。根据实验室测量结果，在 12 例患者中发现了 15 例不良反应。
入住 ICU 的儿童存在临床上显著的细胞色素 P450 介导的 pDDI，其中一些 pDDI 导致了不良的临床结局。临床决策支持系统的使用可以指导临床用药，还需要加强对患者需求的临床监测。
