In vitro metabolism of alachlor by human liver microsomes and human cytochrome P450 isoforms

1999 ◽  
Vol 122 (1) ◽  
pp. 27-39 ◽  
Author(s):  
Scott Coleman ◽  
Siming Liu ◽  
Russell Linderman ◽  
Ernest Hodgson ◽  
Randy L Rose
2004 ◽  
Vol 27 (2) ◽  
pp. 239-245 ◽  
Author(s):  
Hye Young Ji ◽  
Seung-Seok Lee ◽  
Sung-Eun Yoo ◽  
Hosoon Kim ◽  
Dong Ha Lee ◽  
...  

2006 ◽  
Vol 34 (7) ◽  
pp. 1090-1095 ◽  
Author(s):  
Hwa-Kyung Lee ◽  
Joon-Kwan Moon ◽  
Chul-Hee Chang ◽  
Hoon Choi ◽  
Hee-Won Park ◽  
...  

2003 ◽  
Vol 47 (11) ◽  
pp. 3464-3469 ◽  
Author(s):  
Ji-Young Park ◽  
Kyoung-Ah Kim ◽  
Su-Lyun Kim

ABSTRACT The inhibitory effect of chloramphenicol on human cytochrome P450 (CYP) isoforms was evaluated with human liver microsomes and cDNA-expressed CYPs. Chloramphenicol had a potent inhibitory effect on CYP2C19-catalyzed S-mephytoin 4′-hydroxylation and CYP3A4-catalyzed midazolam 1-hydroxylation, with apparent 50% inhibitory concentrations (inhibitory constant [Ki ] values are shown in parentheses) of 32.0 (7.7) and 48.1 (10.6) μM, respectively. Chloramphenicol also weakly inhibited CYP2D6, with an apparent 50% inhibitory concentration (Ki ) of 375.9 (75.8) μM. The mechanism of the drug interaction reported between chloramphenicol and phenytoin, which results in the elevation of plasma phenytoin concentrations, is clinically assumed to result from the inhibition of CYP2C9 by chloramphenicol. However, using human liver microsomes and cDNA-expressed CYPs, we showed this interaction arises from the inhibition of CYP2C19- not CYP2C9-catalyzed phenytoin metabolism. In conclusion, inhibition of CYP2C19 and CYP3A4 is the probable mechanism by which chloramphenicol decreases the clearance of coadministered drugs, which manifests as a drug interaction with chloramphenicol.


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