scholarly journals Cytochrome P450 2C8

2020 ◽  
Author(s):  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 2C8

scholarly journals Influence of Cytochrome P450 (CYP) 2C8 Polymorphisms on the Efficacy and Tolerability of Artesunate-Amodiaquine Treatment of Uncomplicated Plasmodium Falciparum Malaria in Zanzibar

2020 ◽  
Author(s):  
Leyre Pernaute-Lau ◽  
Ulrika Morris ◽  
Mwinyi Msellem ◽  
Andreas Mårtensson ◽  
Anders Björkman ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cytochrome P450 ◽  
Randomized Clinical Trials ◽  
Plasmodium Falciparum Malaria ◽  
Serious Adverse Events ◽  
Cytochrome P450 2C8 ◽  
Significant Difference ◽  
Minor Alleles ◽  
Long Acting ◽  
Parasitological Response

Abstract Background The antimalarial drug amodiaquine, a commonly used long acting partner drug in artemisinin-based combination therapy, is metabolized to active desethyl-amodiaquine (DEAQ) by cytochrome P450 2C8 (CYP2C8). The CYP2C8 gene carries several polymorphisms including the more frequent minor alleles CYP2C8*2 and CYP2C8*3. These minor alleles have been associated with decreased enzymatic activity, slowing the amodiaquine biotransformation towards DEAQ. This study aimed to assess the influence of CYP2C8 polymorphisms on the efficacy and tolerability of artesunate-amodiaquine treatment for uncomplicated Plasmodium falciparum malaria in Zanzibar.Methods We analysed data from 618 children <5 years with uncomplicated P. falciparum malaria enrolled in two randomized clinical trials comparing artesunate-amodiaquine and artemether-lumefantrine in 2002-2005 in Zanzibar. CYP2C8*2 and CYP2C8*3 genotypes were determined by PCR-restriction fragment length polymorphism and assessed in relation to clinical data on treatment outcome and tolerance. Results The allele frequencies of CYP2C8*2 and CYP2C8*3 were 17.5% (95% CI 15.4-19.7%) and 2.7% (95% CI 1.8-3.7%), respectively. There was no significant difference in the proportion of subjects carrying either CYP2C8*2 or CYP2C8*3 alleles amongst those with reinfections (44.1 %; 95% CI 33.8-54.8) or those with recrudescent infections (48.3%; 95% CI 29.4-67.5), compared to those with adequate clinical and parasitological response (36.7 %; 95% CI 30.0-43.9) (P = 0.25 and P = 0.31, respectively). However, patients carrying either the CYP2C8*2 or CYP2C8*3 allele were significantly associated with increased occurrence of non-serious adverse events compare with CYP2C8 *1/*1 wildtype homozygotes (44.9%; 95% CI 36.1-54.0 versus 28.1%; 95% CI 21.9-35.0, respectively; P = 0.003). Conclusions CYP2C8 genotypes did not influence treatment efficacy directly, but the tolerability to ASAQ may be reduced in subjects carrying the CYP2C8*3 and CYP2C8*2 alleles. The importance of this non-negligible association with regards to amodiaquine-based malaria chemotherapy warrants further investigation.

Differential Contribution of Active Site Residues in Substrate Recognition Sites 1 and 5 to Cytochrome P450 2C8 Substrate Selectivity and Regioselectivity†

Biochemistry ◽  
2004 ◽  
Vol 43 (24) ◽  
pp. 7834-7842 ◽  
Author(s):  
Oranun Kerdpin ◽  
David J. Elliot ◽  
Sanford L. Boye ◽  
Donald J. Birkett ◽  
Krongtong Yoovathaworn ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Active Site ◽  
Substrate Recognition ◽  
Substrate Selectivity ◽  
Active Site Residues ◽  
Recognition Sites ◽  
Cytochrome P450 2C8 ◽  
Differential Contribution

Inhibition of Cytochrome P450 2C8-mediated Drug Metabolism by the Flavonoid Diosmetin

2011 ◽  
Vol 26 (6) ◽  
pp. 559-568 ◽  
Author(s):  
Luigi Quintieri ◽  
Pietro Palatini ◽  
Stefano Moro ◽  
Maura Floreani
Keyword(s):  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Cytochrome P450 2C8

Examination of 209 Drugs for Inhibition of Cytochrome P450 2C8

2005 ◽  
Vol 45 (1) ◽  
pp. 68-78 ◽  
Author(s):  
Robert L. Walsky ◽  
Emily A. Gaman ◽  
R. Scott Obach
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 2C8

CYP2C8 polymorphism among the Portuguese

2006 ◽  
Vol 44 (2) ◽  
Author(s):  
Isa Cavaco ◽  
Rita Piedade ◽  
J. Pedro Gil ◽  
Vera Ribeiro
Keyword(s):  
Cytochrome P450 ◽  
Phase I ◽  
Vascular Tone ◽  
Therapeutic Drugs ◽  
Cytochrome P450 2C8 ◽  
Regulation Of Vascular Tone

AbstractCytochrome P450 2C8 (CYP2C8) is a polymorphic phase I drug-metabolising enzyme involved in the metabolism of a wide variety of xenobiotics, as well as a proposed player in the regulation of vascular tone. Polymorphisms in this gene may have an impact on the metabolism of therapeutic drugs such as paclitaxel and verapamil. In this report we have determined the frequencies of the main non-synonymous

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