Cytochrome P450 1A1, 2C9, 2C19, and 3A4 Polymorphisms Account for Interindividual Variability of Toxicological Drug Metabolism in Cynomolgus Macaques

2018 ◽  
Vol 31 (12) ◽  
pp. 1373-1381 ◽  
Author(s):  
Yasuhiro Uno ◽  
Shotaro Uehara ◽  
Norie Murayama ◽  
Hiroshi Yamazaki
2015 ◽  
Vol 44 (3) ◽  
pp. 343-351 ◽  
Author(s):  
T. S. Tracy ◽  
A. S. Chaudhry ◽  
B. Prasad ◽  
K. E. Thummel ◽  
E. G. Schuetz ◽  
...  

2016 ◽  
Vol 67 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Valon Krasniqi ◽  
Aleksandar Dimovski ◽  
Iva Klarica Domjanović ◽  
Ivan Bilić ◽  
Nada Božina

Abstract Interindividual variability in drug metabolism is an important cause of adverse drug reactions and variability in drug efficiency. Polymorphisms of cytochrome P450 (CYPs) genes have a significant effect on drug metabolism and toxicity. This review brings an update about how genetic polymorphisms of CYP2C8 and CYP2C9 enzymes affect the disposition and clinical outcomes of ibuprofen and diclofenac, two of the most common pain relievers. The most common side effects associated with the influence of CYP2C8*3 and CYP2C9*2*3 variants on ibuprofen and diclofenac pharmacokinetics are hepatotoxicity and gastrointestinal bleeding. CYP genotyping may therefore identify patients at increased risk of these adverse reactions, and these patients could have their doses adjusted or start receiving another NSAID that does not share the same metabolic pathways with ibuprofen or diclofenac. However, before genotyping is introduced into regular clinical practice, more research is needed to evaluate the effectiveness of this strategy in improving treatment with ibuprofen and diclofenac.


PEDIATRICS ◽  
2016 ◽  
Vol 137 (Supplement 3) ◽  
pp. 507A-507A
Author(s):  
Sudeepta K Basu ◽  
Renjithkumar Kalikkot Thekkeveedu ◽  
Chun Chu ◽  
Paramhamsa Maturu ◽  
Weiwu Jiang ◽  
...  

2019 ◽  
Vol 18 (23) ◽  
pp. 2042-2055 ◽  
Author(s):  
Neeraj Kumar ◽  
Heerak Chugh ◽  
Damini Sood ◽  
Snigdha Singh ◽  
Aarushi Singh ◽  
...  

Heme is central to functions of many biologically important enzymes (hemoproteins). It is an assembly of four porphyrin rings joined through methylene bridges with a central Fe (II). Heme is present in all cells, and its synthesis and degradation balance its amount in the cell. The deregulations of heme networks and incorporation in hemoproteins lead to pathogenic state. This article addresses the detailed structure, biosynthesis, degradation, and transportation associated afflictions to heme. The article is followed by its roles in various diseased conditions where it is produced mainly as the cause of increased hemolysis. It manifests the symptoms in diseases as it is a pro-oxidant, pro-inflammatory and pro-hemolytic agent. We have also discussed the genetic defects that tampered with the biosynthesis, degradation, and transportation of heme. In addition, a brief about the largest hemoprotein group of enzymes- Cytochrome P450 (CYP450) has been discussed with its roles in drug metabolism.


2004 ◽  
Vol 69 (3) ◽  
pp. 659-673 ◽  
Author(s):  
Petr Hodek ◽  
Tomáš Koblas ◽  
Helena Rýdlová ◽  
Božena Kubíčková ◽  
Miroslav Šulc ◽  
...  

Using chicken antibodies IgY (purified from egg yolks) against mammalian cytochromes P450 and by means of cytochrome P450 marker substrates, we found for the first time the presence of hepatopancreatic cytochrome P450 in crayfishOrconectes limosus(an inducible cytochrome P450 2B-like enzyme) and we were able to detect and quantify cytochrome P450 1A1 in microsomes of human livers. Expression levels of cytochrome P450 1A1 in human livers constituted less than 0.6% of the total hepatic cytochrome P450 complement. The results obtained in our study are clear examples that chicken IgY are suitable for cytochrome P450 detection and quantification. Due to the evolutionary distance, chicken IgY reacts with more epitopes on a mammalian antigen, which gives an amplification of the signal. Moreover, this approach offers many advantages over common mammalian antibody production since chicken egg is an abundant source of antibodies (about 100 mg IgY/yolk) and the egg collection is a non-invasive technique. In the case of antibodies against cytochrome P450 2B4, we documented fast and steady production of highly specific immunoglobulins. Thus, chicken antibodies should be considered as a good alternative to and/or superior substitute for conventional polyclonal antibody produced in mammals.


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