Bořilová Linhartová Petra, Zendulka Ondřej, Janošek Jaroslav, Mlčůchová Natálie, Cvanová Michaela, Daněk Zdeněk, Kroupa Radek, Bartošová Ladislava, Lipový Břetislav
RECETOX, Faculty of Science, Masaryk University, Brno, Czechia.
Clinic of Maxillofacial Surgery, Faculty of Medicine, Institution Shared With University Hospital Brno, Masaryk University, Brno, Czechia.
Front Med (Lausanne). 2022 Jul 11;9:854280. doi: 10.3389/fmed.2022.854280. eCollection 2022.
To this date, there are no recommendations for personalized stress ulcer prophylaxis (SUP) in critical care that would take the patient's individual genetic predispositions into account. Of drugs used for this purpose, proton pump inhibitors (PPIs) are the first-choice drugs in intensive care unit patients. The degradation of proton pump inhibitors is mediated by cytochrome P450 (CYP) enzymes; in particular, CYP2C19 and, to a lesser extent, CYP3A4 are involved. Expression and metabolic activity of, namely in, CYP2C19 is significantly affected by single nucleotide polymorphisms, the drug metabolization rate varies greatly from ultrarapid to poor and likely influences the optimal dosage. As these CYP2C19 predictive phenotypes via haplogenotypes (rs12248560/rs4244285) can be relatively easily determined using the current standard equipment of hospital laboratories, we prepared a set of recommendations for personalized PPI-based stress ulcer prophylaxis taking into account the patient's CYP2C19 predictive phenotype determined in this way. These recommendations are valid, in particular, for European, American and African populations, because these populations have the high representations of the 21917 allele associated with the overexpression of the gene and ultrarapid degradation of PPIs. We propose the gene profiling as a tool for personalized SUP with PPI in critically ill patients.
迄今为止,在重症监护中尚无考虑患者个体遗传易感性的个性化应激性溃疡预防(SUP)建议。在此目的所使用的药物中,质子泵抑制剂(PPI)是重症监护病房患者的首选药物。质子泵抑制剂的降解由细胞色素P450(CYP)酶介导;特别是CYP2C19,以及程度较轻的CYP3A4参与其中。CYP2C19的表达和代谢活性,尤其是在其中,受单核苷酸多态性的显著影响,药物代谢率从超快速到缓慢差异很大,并可能影响最佳剂量。由于使用医院实验室的现有标准设备可以相对容易地通过单倍型(rs12248560/rs4244285)确定这些CYP2C19预测表型,我们在考虑以这种方式确定的患者CYP2C19预测表型的情况下,制定了一套基于个性化PPI的应激性溃疡预防建议。这些建议尤其适用于欧洲、美洲和非洲人群,因为这些人群中与该基因过表达和PPI超快速降解相关的21917等位基因比例较高。我们提议将基因谱分析作为危重症患者使用PPI进行个性化SUP的工具。