scholarly journals Estimation of polymorphisms in the drug-metabolizing enzyme, cytochrome P450 2C19 gene in six major ethnicities of Pakistan

Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 4442-4451
Author(s):  
Sagheer Ahmed ◽  
Saima Gul ◽  
Muhammad Akhlaq ◽  
Abrar Hussain ◽  
Sidrah Tariq Khan ◽  
...  
2002 ◽  
Vol 18 (5) ◽  
pp. 248-253 ◽  
Author(s):  
Janyce F Rogers ◽  
Robert S Kidd

Objective: Genetic code governs cytochrome P450 activity as a consequence, it may influence an individual's response to medications metabolized by these enzymes. Pharmacists have a prominent role in providing education concerning adverse drug reactions and variability in drug response. This investigation assessed the knowledge of a group of pharmacists regarding cytochrome P450 pharmacogenetics. Methods: This observational, cross-sectional study presented a Web–based questionnaire available for completion by pharmacists contacted via E-mail. Fifty-two pharmacists involved with a nationwide home-care facility participated in the study on a volunteer basis. The main outcome measure was percentage score on a 10-question examination. Results: Fifty-two of 171 contacted pharmacists participated in the study, yielding a response rate of 30%. The mean percentage questionnaire score ± SD was 17.5 ± 15.1. Scores were slightly higher for pharmacists with 2 or more pharmacokinetic classes in their formal education (p < 0.02). Conclusions: Understanding the principles of pharmacogenetics will allow pharmacists to appreciate that patients respond differently to certain medications as influenced by genetic variations encoding drug-metabolizing enzyme activity. As a consequence, some patients will have a normal therapeutic response, whereas others may experience drug toxicity or therapeutic inefficacy when given the same dose of a drug. This study determined, albeit with many limitations, that there is likely a need for improved availability of pharmacogenetic continuing education programs.


2007 ◽  
Vol 19 (Supplement) ◽  
pp. 210-210
Author(s):  
Aya Katsuura ◽  
Satoshi Matsuo ◽  
Yoshiko Nagata ◽  
Hideko Kanazawa

Author(s):  
Przemysław J. Danek ◽  
Agnieszka Basińska-Ziobroń ◽  
Jacek Wójcikowski ◽  
Władysława A. Daniel

2018 ◽  
Vol 7 (4) ◽  
pp. 29 ◽  
Author(s):  
Yee Ung ◽  
Chin Ong ◽  
Yan Pan

Cytochrome P450 (CYP) is a critical drug-metabolizing enzyme superfamily. Modulation of CYP enzyme activities has the potential to cause drug–drug/herb interactions. Drug–drug/herb interactions can lead to serious adverse drug reactions (ADRs) or drug failures. Therefore, there is a need to examine the modulatory effects of new drug entities or herbal preparations on a wide range of CYP isoforms. The classic method of quantifying CYP enzyme activities is based on high-performance liquid chromatography (HPLC), which is time- and reagent-consuming. In the past two decades, high-throughput screening methods including fluorescence-based, luminescence-based, and mass-spectrometry-based assays have been developed and widely applied to estimate CYP enzyme activities. In general, these methods are faster and use lower volume of reagents than HPLC. However, each high-throughput method has its own limitations. Investigators may make a selection of these methods based on the available equipment in the laboratory, budget, and enzyme sources supplied. Furthermore, the current high-throughput systems should look into developing a reliable automation mechanism to accomplish ultra-high-throughput screening in the near future.


2014 ◽  
Vol 17 (3) ◽  
pp. 294 ◽  
Author(s):  
Teresa W Tam ◽  
Rui Liu ◽  
Ammar Saleem ◽  
John Thor Arnason ◽  
Anthony Krantis ◽  
...  

PURPOSE: Thirty-five commercially available Camellia sinensis (black and green) and herbal leisure teas and an assortment of Traditional Chinese medicinal teas were randomly selected and examined for their potential to inhibit the drug metabolizing enzyme cytochrome P450 3A4 (CYP3A4). The study was then extended to examine CYP2D6*1 and CYP2D6*10. METHODS: Microtiter fluorometric assays were utilized to examine the potential for the teas to inhibit CYP-mediated metabolism. Aqueous or alcoholic extracts of the dried tea plant material were examined. METHODS: Most of the black and green leisure teas generally inhibited CYP3A4 more than the Chinese medicinal teas. The medicinal Chinese teas were generally more inhibitory towards CYP3A4 compared to the CYP2D6 isozymes, and the aqueous extracts displayed more potency than the alcoholic extracts. CONCLUSIONS: Tea whether used for leisure or medicinal purposes has the potential to inhibit CYP3A4-mediated drug metabolism particularly black tea.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.


2019 ◽  
Vol 20 (17) ◽  
pp. 4245 ◽  
Author(s):  
Irina F. Sevrioukova

Human cytochrome P450 3A4 (CYP3A4) is the most important drug-metabolizing enzyme. Some drugs and natural compounds can act as suicide (mechanism-based) inactivators of CYP3A4, leading to unanticipated drug-drug interactions, toxicity and therapeutic failures. Despite significant clinical and toxicological implications, the mechanism-based inactivation remains incompletely understood. This study provides the first direct insights into the interaction of CYP3A4 with three suicide substrates: mibefradil, an antihypertensive drug quickly withdrawn from the market; a semi-synthetic antibiotic azamulin; and a natural furanocoumarin, 6′,7′-dihydroxybergamottin. Novel structural findings help better understand the suicide substrate binding and inhibitory mechanism, and can be used to improve the predictability of the binding ability, metabolic sites and inhibitory/inactivation potential of newly developed drugs and other chemicals relevant to public health.


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