Cytochromes P450 are major metabolic enzymes involved in the biotransformation of xenobiotics. The majority of xenobiotics are metabolized in the liver, in which the highest levels of cytochromes P450 are expressed. Flavonoids are natural compounds t...
Background/Objectives: In Ecuador, the prevalence of type 2 diabetes mellitus (T2DM) is the second leading cause of death after ischemic heart disease. Genetic variability in protein-coding genes, single nucleotide variants (SNVs), influences the res...
Background/Aims: across protein-coding genes, single nucleotide allelic variants (SNVs) affect antidiabetic drug pharmacokinetics, thus contributing to interindividual variability in drug response. SNV frequencies vary across different populations. S...
The antiplatelet agent clopidogrel is listed by the FDA as a strong clinical index inhibitor of cytochrome P450 (CYP) 2C8 and weak clinical inhibitor of CYP2B6. Moreover, clopidogrel is a substrate of—among others—CYP2C19 and CYP3A4. This...
Cytochrome P450 2C8 (CYP2C8) epoxygenase is responsible for the metabolism of over 60 clinically relevant drugs, notably the anticancer drug Taxol (paclitaxel, PAC). Specifically, there are naturally occurring polymorphisms, CYP2C8*2 and CYP2C8*3, th...
Pharmaceutical excipients (PEs) are substances included in drug formulations. Recent studies have revealed that some PEs can affect the activity of metabolic enzymes and drug transporters; however, the effects of PEs on CYP2C8 and its interaction pot...
Background/Objectives: Research on pharmacogenetic variability in response to prescribed drugs and across ethnic groups is essential for personalized medicine, particularly in admixed and unstudied populations. For the first time, this study examines...
Background: Recent studies have associated the presence of the CYP2C:TG haplotype with increased metabolism of CYP2C19 substrates such as escitalopram and sertraline, suggesting a potential regulatory interaction between CYP2C18 and CYP2C19. However,...
Phenytoin (PHT) oxidative route leads to its main metabolite p-hydroxyphenytoin (p-HPPH), by means of CYP2C9 and CYP2C19. Formation of p-HPPH proceeds via a reactive arene-oxide intermediate. This intermediate can also be converted into PHT dihydrodi...
Background/Objective: Cerivastatin (Cer), a cholesterol-lowering statin, was withdrawn from the market due to fatal cases of rhabdomyolysis, particularly when co-administered with gemfibrozil (Gem), a strong CYP2C8 inhibitor. However, the pharmacokin...
Background/Objectives: Epilepsy is characterized by recurrent, unprovoked, self-limiting seizures of genetic, acquired, or unknown origin. It affects more than 50 million people worldwide. The prevalence in Peru is 11.9–32.1 per 1000 people. Ou...
In the Amazon, the treatment for Plasmodium vivax is chloroquine plus primaquine. However, this regimen is limited due to the risk of acute hemolytic anemia in glucose-6-phosphate dehydrogenase deficiency. Primaquine is a prodrug that requires conver...
Trimethoprim is a frequently-prescribed antibiotic and therefore likely to be co-administered with other medications, but it is also a potent inhibitor of multidrug and toxin extrusion protein (MATE) and a weak inhibitor of cytochrome P450 (CYP) 2C8....
Background/Objectives: Venlafaxine has been reported to exhibit significant interindividual pharmacokinetic heterogeneity across populations, which has been linked to cytochrome P450 polymorphisms and clinical factors. This study aimed to assess the...
Background and Objective. VKORC1, CYP2C9, and CYP4F2 are known to be responsible for the metabolism of warfarin. The aim was to explore the frequencies of these genotypes in the Russian population and compare the results with those for other populati...
CYP2D6 and CYP2C19 enzymes are essential in the metabolism of antidepressants and antipsychotics. Genetic variation in these genes may increase risk of adverse drug reactions. Antidepressants and antipsychotics have previously been associated with ri...
CYP2D6 and CYP2C19 are enzymes of essential significance for the pharmacokinetics of a multitude of commonly used antidepressants, antipsychotics, antiemetics, β-blockers, opioids, antiestrogen, antacids, etc. Polymorphisms in the respective gen...
A recently discovered haplotype—CYP2C:TG—determines the ultrarapid metabolism of several CYP2C19 substrates. The platelet inhibitor clopidogrel requires CYP2C19-mediated activation: the risk of ischemic events is increased in patients wit...
The Punica granatum L. (pomegranate) fruit juice contains large amounts of polyphenols, mainly tannins such as ellagitannin, punicalagin, and punicalin, and flavonoids such as anthocyanins, flavan-3-ols, and flavonols. These constituents have high an...
CYP2C9 and CYP2C19 are major CYP450 enzymes that heavily influence the hepatic metabolism and bioactivation of many medications, including over-the-counter and narrow therapeutic index drugs. Compared to the wild-type alleles, genetic variants in eit...
Background: Helicobacter pylori eradication containing the potassium-competitive acid blocker, vonoprazan, achieves a higher eradication rate than therapy with proton pump inhibitors (PPIs). Because vonoprazan is mainly metabolized by CYP3A4/5, CYP g...
Background/Objectives: Cirrhosis significantly alters physiological function and drug metabolism, particularly for medications primarily metabolized by CYP2C19 and CYP3A4. This study aims to establish a physiologically based pharmacokinetic (PBPK) mo...
Background: A promoter variable number tandem repeat polymorphism (pVNTR) of CYP2C9 is described with three types of fragments: short (pVNTR-S), medium (pVNTR-M) and long (pVNTR-L). The pVNTR-S allele reduces the CYP2C9 mRNA level in the human liver,...
Genetic variability in CYP2C19 may be associated with both lack of efficacy and toxicity of drugs due to its different metabolic status based on the presence of particular alleles. This literature review summarizes current knowledge relative to the a...
Single nucleotide polymorphisms in drug-metabolizing genes may affect tacrolimus pharmacokinetics. Here, we investigated the influence of genotypes of CYP3A5, CYP2C19, and POR on the concentration/dose (C/D) ratio of tacrolimus and episodes of acute...
CYP2C9 is the most abundant CYP2C subfamily enzyme in human liver and the most important contributor from this subfamily to drug metabolism. Polymorphisms resulting in decreased enzyme activity are common in the CYP2C9 gene and this, combined with na...
Of the Cytochrome P450 enzymes, the CYP2C9 variant is very important in the metabolism of several human drugs, acting as a natural bioscavenger. Previously, CYP2C9 was shown to convert the thion (P=S) to the oxon (P=O) form for some organophosphorus...
Pharmacogenomic (PGx) testing to inform antidepressant medication selection and dosing is gaining attention from healthcare professionals, patients, and payors in Australia. However, there is often uncertainty regarding which test is most suitable fo...
Variability in response to antiplatelet therapy can be explained in part by pharmacogenomics, particularly of the CYP450 enzyme encoded by CYP2C19. Loss-of-function and gain-of-function variants help explain these interindividual differences. Individ...
Cytochromes P450 (CYP) are the main actors in the oxidation of xenobiotics and play a crucial role in drug safety, persistence, bioactivation, and drug-drug/food-drug interaction. This work aims to develop Quantitative Structure-Activity Relationship...
Carbon nanostructures have recently gained significant interest from scientists due to their unique physicochemical properties and low toxicity. They can accumulate in the liver, which is the main expression site of cytochrome P450 (CYP450) enzymes....
The antidiabetic drug gliclazide is partly metabolized by CYP2C19, the main enzyme involved in omeprazole metabolism. The aim of the study was to explore the interaction between omeprazole and gliclazide in relation to CYP2C19 phenotype using physiol...
CYP2C19 is a highly polymorphic gene responsible for the metabolism of commonly used drugs. CYP2C19*1, the wild-type allele, is associated with normal enzyme activity, whereas CYP2C19*2 and CYP2C19*17 lead to null and increased enzyme activity, respe...
Polymorphism in cytochrome P450 (CYP) 2C9 enzyme is known to cause significant inter-individual differences in drug response and occurrence of adverse drug reactions. Different alleles of the CYP2C9 gene have been identified, but the notable alleles...
Diazepam is a benzodiazepine widely prescribed for the management of patients with severe alcohol withdrawal syndrome to prevent agitation, withdrawal seizures, and delirium tremens. Despite standard dosing of diazepam, a subset of patients experienc...
Currently, the therapeutic effect of clopidogrel differs considerably among individuals and is thought to be closely related to the genetic polymorphism of CYP2C19. The CYP2C19*2 gene can reduce the antiplatelet aggregation effect of clopidogrel, whi...
CYP2C9 metabolizes approximately 20% of clinically administered drugs. Several single-nucleotide polymorphisms (SNPs) of CYP2C9 (e.g., *2, *3, *8, and rs12777823) are used as biomarkers to predict CYP2C9 activity. However, a large proportion of varia...
CYP2C19 polymorphisms are important factors for proton pump inhibitor-based therapy. We examined the CYP2C19 genotypes and analyzed the distribution among ethnicities and clinical outcomes in Indonesia. We employed the polymerase chain reaction-restr...
The risk factors for stroke, a fatal disease, include type two diabetes, hypertension, and genetic influences. Small vessel occlusion (SVO) can be affected by epigenetic alterations, but an association between SVO and the methylation of cytochrome P4...
A clinical effect of warfarin depends on highly polymorphic drug-metabolizing (CYP2C9) and drug-target (VKORC1) enzymes. The objective of this study was to investigate the impact of CYP2C9*2, CYP2C9*3, and VKORC1 (G-1639A) polymorphisms on the variab...
The effectiveness of lipid-lowering therapies may be insufficient in high-risk cardiovascular patients and depends on the genetic variability of drug-metabolizing enzymes. Customizing statin therapy, including treatment with atorvastatin, may improve...
Major depressive disorder (MDD) affects over 300 million people globally and has a multifactorial etiology. The CYP2C19 enzyme, involved in metabolizing certain antidepressants, can influence treatment response. Following the PRISMA protocol and PECO...
A variable number tandem repeat polymorphism has been described in the CYP2C9 promoter (pVNTR) with three types of fragments: short (pVNTR-S), medium (pVNTR-M), and long (pVNTR-L). The pVNTR-S allele appears in strong linkage disequilibrium (LD) with...
Background and objectives: Warfarin is a commonly used anticoagulant with a narrow therapeutic index that requires a precise dose to achieve efficacy and safety. Genetic variations in the CYP2C9 and VKORC1 genes significantly contribute to individual...
Although the functional roles of M1 and M2 macrophages in the immune response and drug resistance are important, the expression and role of cytochrome P450s (CYPs) in these cells remain largely unknown. Differential expression of the 12 most common C...
This study aimed to investigate the influence of CYP2C9 genetic polymorphisms on the pharmacokinetics of losartan and its active metabolite, E-3174, through a systematic review and meta-analysis. Eight studies published before March 2021 were include...
Warfarin is an oral anticoagulant frequently used in the treatment of different cardiovascular diseases. Genetic polymorphisms in the CYP2C9 and VKORC1 genes have produced variants with altered catalytic properties. A total of 212 cardiovascular pati...
Polymorphisms in CYP2C9 can significantly interfere with the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of nonsteroidal anti-inflammatory drugs (NSAIDs), including naproxen. The present research aimed to study the PK/PD parameters of na...
During the past decades, there have been continuous attempts in the prediction of metabolism mediated by cytochrome P450s (CYP450s) 3A4, 2D6, and 2C9. However, it has indeed remained a huge challenge to accurately predict the metabolism of xenobiotic...
Background/Objectives: Hypertension is a pathological condition characterized by elevated systolic and/or diastolic blood pressure. A range of pharmacotherapeutic agents are available to treat this condition and prevent complications, including the a...
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