Cytochrome P-450 CYP2B6

Publication Title: 
British Journal of Clinical Pharmacology

AIMS: The study aimed to identify the specific human cytochrome P450 (CYP450) enzymes involved in the metabolism of artemisinin. METHODS: Microsomes from human B-lymphoblastoid cell lines transformed with individual CYP450 cDNAs were investigated for their capacity to metabolize artemisinin. The effect on artemisinin metabolism in human liver microsomes by chemical inhibitors selective for individual forms of CYP450 was investigated.

Author(s): 
Svensson, U. S.
Ashton, M.
Publication Title: 
European Journal of Clinical Pharmacology

OBJECTIVE: Cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of artemisinin drugs, a novel series of antimalarials. Our aim was to analyze the prevalence of the most commonly observed CYP2B6 alleles in malaria-endemic populations of West Africa (WA) and Papua New Guinea (PNG). METHODS: Using a post-PCR ligation detection reaction-fluorescent microsphere assay, frequencies of CYP2B6*1A, *2, *3, *4, *5, *6, *7, and *9 were determined in WA (n=166) and PNG (n=174).

Author(s): 
Mehlotra, Rajeev K.
Ziats, Mark N.
Bockarie, Moses J.
Zimmerman, Peter A.
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

Artemether (AM) is one of the most effective antimalarial drugs. The elimination half-life of AM is very short, and it shows large interindividual variability in pharmacokinetic parameters. The aim of this study was to identify cytochrome P450 (P450) isozymes responsible for the demethylation of AM and to evaluate functional differences between 26 CYP2B6 allelic variants in vitro. Of 14 recombinant P450s examined in this study, CYP2B6 and CYP3A4 were primarily responsible for production of the desmethyl metabolite dihydroartemisinin.

Author(s): 
Honda, Masashi
Muroi, Yuka
Tamaki, Yuichiro
Saigusa, Daisuke
Suzuki, Naoto
Tomioka, Yoshihisa
Matsubara, Yoichi
Oda, Akifumi
Hirasawa, Noriyasu
Hiratsuka, Masahiro
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

Artemisinin drugs have become the first-line antimalarials in areas of multidrug resistance. However, monotherapy with artemisinin drugs results in comparatively high recrudescence rates. Autoinduction of cytochrome P450 (P450)-mediated metabolism, resulting in reduced exposure, has been supposed to be the underlying mechanism.

Author(s): 
Xing, Jie
Kirby, Brian J.
Whittington, Dale
Wan, Yakun
Goodlett, David R.
Publication Title: 
PloS One

In this study, we investigated the influence of single nucleotide polymorphisms on the conformation of mutated cytochrome P450 (CYP) 2B6 proteins using molecular dynamics (MD) simulation. Some of these mutations influence drug metabolism activities, leading to individual variations in drug efficacy and pharmacokinetics. Using computational docking, we predicted the structure of the complex between the antimalarial agent artemether and CYP2B6 whose conformations were obtained by MD simulation.

Author(s): 
Kobayashi, Kana
Takahashi, Ohgi
Hiratsuka, Masahiro
Yamaotsu, Noriyuki
Hirono, Shuichi
Watanabe, Yurie
Oda, Akifumi
Publication Title: 
Malaria Journal

BACKGROUND: Artequick is a relatively inexpensive artemisinin (Qing-hao-su; QHS)-based combination therapy (ACT) that contains QHS and piperaquine (PQ), which has not been widely used because of the decreased concentration level of QHS after repeated oral administrations for five to seven days as a monotherapy. This study was designed to evaluate the potential auto-induction metabolism of QHS in healthy Chinese adults after a two-day oral administration of QHS-PQ. The effect of QHS-PQ on the activity of the CYP2B6 and CYP3A4 was also investigated.

Author(s): 
Zang, Meitong
Zhu, Fanping
Li, Xinxiu
Yang, Aijuan
Xing, Jie
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

CYP2A6, CYP2B6, and UGT1A9 genetic polymorphisms and treatment response after a three-day course of artesunate-mefloquine was investigated in 71 Burmese patients with uncomplicated Plasmodium falciparum malaria. Results provide evidence for the possible link between CYP2A6 and CYP2B6 polymorphisms and plasma concentrations of artesunate/dihydroartemisinin and treatment response.

Author(s): 
Phompradit, Papichaya
Muhamad, Poonuch
Cheoymang, Anurak
Na-Bangchang, Kesara
Publication Title: 
Archives of Iranian Medicine

BACKGROUND: Genetic polymorphisms in the cytochrome P450 2B6 (CYP2B6) gene could influence therapeutic outcomes of CYP2B6-metabolized drugs such as artemisinin, nevirapine (NVP), and efavirenz (EFV). The main objective of the present study was to analyze the frequency of the most common allele of CYP2B6*1 to *7 and *9 in Iranian Baluchi population and also to compare the frequencies of these polymorphisms with those reported in different ethnic groups. METHODS: A total of 206 healthy, unrelated, subjects were participated in this study.

Author(s): 
Zakeri, Sedigheh
Amiri, Nasrin
Pirahmadi, Sakineh
Dinparast Djadid, Navid
Publication Title: 
Antimicrobial Agents and Chemotherapy

Malaria patients are frequently coinfected with HIV and mycobacteria causing tuberculosis, which increases the use of coadministered drugs and thereby enhances the risk of pharmacokinetic drug-drug interactions. Activation of the pregnane X receptor (PXR) by xenobiotics, which include many drugs, induces drug metabolism and transport, thereby resulting in possible attenuation or loss of the therapeutic responses to the drugs being coadministered. While several artemisinin-type antimalarial drugs have been shown to activate PXR, data on nonartemisinin-type antimalarials are still missing.

Author(s): 
Piedade, Rita
Traub, Stefanie
Bitter, Andreas
Nüssler, Andreas K.
Gil, José P.
Schwab, Matthias
Burk, Oliver
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