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细胞色素P450诱导剂和抑制剂的处方模式及其在现实世界中的潜在药物相互作用:一项横断面研究

Prescription Patterns of Inducers and Inhibitors of Cytochrome P450 and Their Potential Drug Interactions in the Real World: A Cross-Sectional Study.

作者信息

Valladales-Restrepo Luis Fernando, Ospina-Cano Juan Alberto, Aristizábal-Carmona Brayan Stiven, Machado-Alba Jorge Enrique

机构信息

Grupo de Investigación en Farmacoepidemiología y Farmacovigilancia, Universidad Tecnológica de Pereira-Audifarma S.A, Calle 105 No. 14-140, 660003, Pereira, Risaralda, Colombia.

Grupo de Investigación Biomedicina, Facultad de Medicina, Fundación Universitaria Autónoma de las Américas, Pereira, Colombia.

出版信息

Drugs Real World Outcomes. 2024 Dec;11(4):617-626. doi: 10.1007/s40801-024-00450-1. Epub 2024 Sep 7.

Abstract

INTRODUCTION

Both the induction and inhibition of cytochrome P450 are associated with multiple pharmacological interactions, which can lead to loss of efficacy or increase the risk of adverse drug reactions.

OBJECTIVE

The aim was to determine the prescription patterns of cytochrome P450-inducing and -inhibiting drugs and their contraindicated and major pharmacological interactions in a group of patients from Colombia.

METHODS

This cross-sectional observational study included patients who received drugs that induce or inhibit metabolism and examined their contraindicated and major pharmacological interactions. The patients were identified from a population-based database of drug dispensing. Patients were included between December 1 and December 31, 2021. Inhibitors and inducers of cytochrome P450 were classified based on FDA (Food and Drug Administration) guidelines. Drug interactions were identified using the Micromedex® database. Descriptive, bivariate and multivariable analysis was performed.

RESULTS

A total of 63,433 patients were analyzed. Antiseizure medications (35.9%) and antifungals (27.6%) were the most used inducers and inhibitors. A total of 30.1% of patients had potential contraindicated or greater interactions. The following factors were associated with a higher probability of presenting a potential pharmacological interaction: being male (OR 1.14; 95% CI 1.10-1.19), aged 18-39 years (OR 1.77; 95% CI 1.67-1.89) or 40-64 years (OR 1.64; 95% CI 1.56-1.72), having neurological diseases (OR 1.28; 95% CI 1.21-1.35), having psychiatric diseases (OR 3.84; 95% CI 3.58-4.13), having rheumatologic diseases (OR 1.32; 95% CI 1.23-1.41), receiving comedications with statins (OR 1.14; 95% CI 1.08-1.19), receiving comedications with analgesics (OR 1.33; 95% CI 1.27-1.38), receiving comedications with antiparasitics (OR 2.88; 95% CI 2.66-3.11) and an increase in the number of medications (OR 1.24; 95% CI 1.23-1.25).

CONCLUSION

Among the users of cytochrome P450 inhibitors and inducers, potential contraindications and greater interactions are very common, especially in men under 65 years of age with comorbidities and polypharmacy.

摘要

引言

细胞色素P450的诱导和抑制均与多种药物相互作用相关,这可能导致疗效丧失或增加药物不良反应的风险。

目的

旨在确定哥伦比亚一组患者中细胞色素P450诱导剂和抑制剂的处方模式及其禁忌和主要药物相互作用。

方法

这项横断面观察性研究纳入了接受诱导或抑制代谢药物的患者,并检查了他们的禁忌和主要药物相互作用。患者从基于人群的药物配药数据库中识别。纳入2021年12月1日至12月31日期间的患者。细胞色素P450的抑制剂和诱导剂根据美国食品药品监督管理局(FDA)的指南进行分类。使用Micromedex®数据库识别药物相互作用。进行了描述性、双变量和多变量分析。

结果

共分析了63433名患者。抗癫痫药物(35.9%)和抗真菌药物(27.6%)是最常用的诱导剂和抑制剂。共有30.1%的患者存在潜在禁忌或更大的相互作用。以下因素与出现潜在药物相互作用的可能性较高相关:男性(比值比1.14;95%置信区间1.10 - 1.19)、年龄在18 - 39岁(比值比1.77;95%置信区间1.67 - 1.89)或40 - 64岁(比值比1.64;95%置信区间1.56 - 1.72)、患有神经系统疾病(比值比1.28;95%置信区间1.21 - 1.35)、患有精神疾病(比值比3.84;95%置信区间3.58 - 4.13)、患有风湿性疾病(比值比1.32;95%置信区间1.23 - 1.41)、接受与他汀类药物的合并用药(比值比1.

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