CYP2C19 Gene Profiling as a Tool for Personalized Stress Ulcer Prophylaxis With Proton Pump Inhibitors in Critically Ill Patients - Recommendations Proposal

Abstract

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 CYP2C19 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 CYP2C19*17 allele associated with the overexpression of the CYP2C19 gene and ultrarapid degradation of PPIs. We propose the CYP2C19 gene profiling as a tool for personalized SUP with PPI in critically ill patients.

Safety, Tolerability, and Pharmacokinetics of Anaprazole, a Novel Proton Pump Inhibitor, in Healthy Chinese Subjects

“…These PPIs are extensively used in the management of both acute and chronic gastric acid‐related diseases, including peptic ulcers, gastroesophageal reflux disease, upper gastrointestinal bleeding, and Zollinger‐Ellison syndrome, as well as for eradicating infection with Helicobacter pylori 4,5 . Given that PPIs are primarily metabolized by hepatic cytochrome 450 (CYP) 2C19, the genetic polymorphism of CYP2C19 can influence the pharmacokinetics of PPIs, leading to interindividual variability of drug efficacy, toxicity, and even adverse drug‐drug interactions 6,7 . Rabeprazole, a new generation of PPI, exhibits unique pharmacokinetic characteristics.…”