Quantitative Prediction of the Impact of Drug Interactions and Genetic Polymorphisms on Cytochrome P450 2C9 Substrate Exposure

2013 ◽  
Vol 52 (3) ◽  
pp. 199-209 ◽  
Author(s):  
Anne-Charlotte Castellan ◽  
◽  
Michel Tod ◽  
François Gueyffier ◽  
Mélanie Audars ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Genetic Polymorphisms ◽  
Quantitative Prediction ◽  
Cytochrome P450 2C9 ◽  
The Impact

High Confidence Predictions of Drug−Drug Interactions: Predicting Affinities for Cytochrome P450 2C9 with Multiple Computational Methods

2008 ◽  
Vol 51 (3) ◽  
pp. 648-654 ◽  
Author(s):  
Matthew G. Hudelson ◽  
Nikhil S. Ketkar ◽  
Lawrence B. Holder ◽  
Timothy J. Carlson ◽  
Chi-Chi Peng ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Computational Methods ◽  
Cytochrome P450 2C9 ◽  
High Confidence

Quantitative Prediction of Cytochrome P450 (CYP) 2D6-Mediated Drug Interactions

2011 ◽  
Vol 50 (8) ◽  
pp. 519-530 ◽  
Author(s):  
Michel Tod ◽  
Sylvain Goutelle ◽  
Fannie Clavel-Grabit ◽  
Grégoire Nicolas ◽  
Bruno Charpiat
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Quantitative Prediction ◽  
Cyp 2D6

Role of Genetic Polymorphisms of Cytochrome P450 2C19 in Pantoprazole Metabolism and Pantoprazole-based Helicobacter pylori Eradication Regimens

2020 ◽  
Vol 21 (11) ◽  
pp. 830-837 ◽  
Author(s):  
Paulius Jonaitis ◽  
Laimas Jonaitis ◽  
Juozas Kupcinskas
Keyword(s):  
Helicobacter Pylori ◽  
Cytochrome P450 ◽  
Genetic Polymorphisms ◽  
Gene Polymorphisms ◽  
Routine Practice ◽  
Therapeutic Effects ◽  
Helicobacter Pylori Eradication ◽  
P450 Gene ◽  
The Impact

Background: Cytochrome P450 (CYP450) enzymes play an important role in the metabolism of 70-80% of the currently used medications, including proton pump inhibitors. There are some data analyzing the impact of gene polymorphisms of CYP450 enzymes on most widely used PPIs, such as omeprazole, however, the data on pantoprazole are highly lacking. Objective: To summarize the most recent publications and studies on the role of polymorphisms of the genes encoding CYP450 enzyme 2C19 in the metabolism of pantoprazole and pantoprazole based Helicobacter pylori eradication regimens. Methods: We performed a non-systematic search of the available literature on the selected topic. Results and conclusion: The data on cytochrome P450 gene polymorphisms and their role in pantoprazole metabolism and pantoprazole based Helicobacter pylori eradication remain conflicting. Individual differences in pantoprazole metabolism might be partly related to genetic polymorphisms of CYP450 enzymes. Most of the studies support the observation that cytochrome 2C19 polymorphisms have an impact on the pharmacokinetics of pantoprazole and its therapeutic effects: poor metabolizers of PPIs are more likely to have a better response to pantoprazole therapy and achieve better H. pylori eradication rates compared to rapid metabolizers. The determination of alleles that are associated with decreased (e.g., *2, *3 alleles) or increased (e.g., *17 allele) cytochrome 2C19 enzyme activity might be used as predictive factors for the potential of acid suppression and the success of Helicobacter pylori eradication. Overall, currently available data do not provide robust evidence, therefore, the application of genetic polymorphisms of cytochrome enzymes in clinical practice still cannot be recommended as routine practice for personalized pantoprazole prescription strategies.

scholarly journals Combined Impact of Inflammation and Pharmacogenomic Variants on Voriconazole Trough Concentrations: A Meta-Analysis of Individual Data

2021 ◽  
Vol 10 (10) ◽  
pp. 2089
Author(s):  
Léa Bolcato ◽  
Charles Khouri ◽  
Anette Veringa ◽  
Jan Willem C. Alffenaar ◽  
Takahiro Yamada ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Genetic Polymorphisms ◽  
Protein Level ◽  
Cytochromes P450 ◽  
Individual Data ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Cytochrome P450 2C19 ◽  
Trough Concentrations ◽  
The Impact

Few studies have simultaneously investigated the impact of inflammation and genetic polymorphisms of cytochromes P450 2C19 and 3A4 on voriconazole trough concentrations. We aimed to define the respective impact of inflammation and genetic polymorphisms on voriconazole exposure by performing individual data meta-analyses. A systematic literature review was conducted using PubMed to identify studies focusing on voriconazole therapeutic drug monitoring with data of both inflammation (assessed by C-reactive protein level) and the pharmacogenomics of cytochromes P450. Individual patient data were collected and analyzed in a mixed-effect model. In total, 203 patients and 754 voriconazole trough concentrations from six studies were included. Voriconazole trough concentrations were independently influenced by age, dose, C-reactive protein level, and both cytochrome P450 2C19 and 3A4 genotype, considered individually or through a combined genetic score. An increase in the C-reactive protein of 10, 50, or 100 mg/L was associated with an increased voriconazole trough concentration of 6, 35, or 82%, respectively. The inhibitory effect of inflammation appeared to be less important for patients with loss-of-function polymorphisms for cytochrome P450 2C19. Voriconazole exposure is influenced by age, inflammatory status, and the genotypes of both cytochromes P450 2C19 and 3A4, suggesting that all these determinants need to be considered in approaches of personalization of voriconazole treatment.

scholarly journals EFFECT OF CYTOCHROME P450 2C9 GENE POLYMORPHISMS ON INDIVIDUAL SENSITIVITY TO GLICLAZIDE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

2015 ◽  
Vol 7 (1) ◽  
pp. 28-33
Author(s):  
M Abulula ◽  
V L Baranov ◽  
N V Vorokhobina
Keyword(s):  
Type 2 Diabetes ◽  
Cytochrome P450 ◽  
Effective Dose ◽  
Dose Titration ◽  
Cytochrome P450 2C9 ◽  
Individual Sensitivity ◽  
Polymorphic Allele ◽  
Target Values ◽  
The Impact

Cytochrome P450 2C9, encoded by the gene CYP2C9 , is a key enzyme for the metabolism of most sulfonylurea (SU). It is known that the polymorphisms CYP2C9*2 and CYP2C9*3 are associated with decreased activity of cytochrome, which leads to an increase in plasma concentrations of SU and reduction in its clearance. The aim of the study was to assess the impact CYP2C9 polymorphisms on individual sensitivity to gliclazide in patients with type 2 diabetes. The study included 74 patients with newly diagnosed diabetes. For all patients gliclazide in a dose of 30 or 60 mg/day was prescribed. Dose titration was carried out for 6 months of observation. If necessary other glucose-lowering therapy (a combination of drugs or insulin) were prescribed. Following the results of study, all patients had achieved the target values of Hb A1c. In comparison with patients who had a polymorphic allele in the gene, patients with wild-type CYP2C9 had lower effective dose of gliclazide, more often required prescription of large (90-120 mg) doses of drug or other antihyperglycemic therapy. Conclusion: The presence of a polymorphic allele in the gene CYP2C9 in homo- or heterozygous state is associated with a decrease in the effective dose of gliclazide, used as monotherapy in patients with type 2 diabetes.

Genetic polymorphisms of cytochrome P450 2C9 causing reduced phenprocoumon (S)-7-hydroxylationin vitroandin vivo

Xenobiotica ◽  
2004 ◽  
Vol 34 (9) ◽  
pp. 847-859 ◽  
Author(s):  
M. Ufer ◽  
B. Kammerer ◽  
R. Kahlich ◽  
J. Kirchheiner ◽  
ü. Yasar ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Genetic Polymorphisms ◽  
Cytochrome P450 2C9

Pharmacokinetics of glimepiride and cytochrome P450 2C9 genetic polymorphisms

2005 ◽  
Vol 78 (1) ◽  
pp. 90-92 ◽  
Author(s):  
R WANG ◽  
K CHEN ◽  
S WEN ◽  
J LI ◽  
S WANG
Keyword(s):  
Cytochrome P450 ◽  
Genetic Polymorphisms ◽  
Cytochrome P450 2C9

A Refined 3-Dimensional QSAR of Cytochrome P450 2C9:  Computational Predictions of Drug Interactions

2000 ◽  
Vol 43 (15) ◽  
pp. 2789-2796 ◽  
Author(s):  
Sreedhara Rao ◽  
Ron Aoyama ◽  
Michael Schrag ◽  
William F. Trager ◽  
Allan Rettie ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Cytochrome P450 2C9 ◽  
3 Dimensional ◽  
Computational Predictions
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