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Molecules 2012, 17(1), 851-860; doi:10.3390/molecules17010851
Article

Effect of Efavirenz on UDP-Glucuronosyltransferase 1A1, 1A4, 1A6, and 1A9 Activities in Human Liver Microsomes

1,†, 1,2,†, 1, 2 and 1,*
Received: 28 October 2011; in revised form: 9 January 2012 / Accepted: 10 January 2012 / Published: 17 January 2012
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Abstract: Efavirenz is a non-nucleoside reverse transcriptase inhibitor used for the treatment of human immunodeficiency virus type 1 infections. Drug interactions of efavirenz have been reported due to in vitro inhibition of CYP2C9, CYP2C19, CYP3A4, and UDP-glucuronosyltransferase 2B7 (UGT2B7) and in vivo CYP3A4 induction. The inhibitory potentials of efavirenz on the enzyme activities of four major UDP-glucuronosyltransferases (UGTs), 1A1, 1A4, 1A6, and 1A9, in human liver microsomes were investigated using liquid chromatography-tandem mass spectrometry. Efavirenz potently inhibited UGT1A4-mediated trifluoperazine N-glucuronidation and UGT1A9-mediated propofol glucuronidation, with Ki values of 2.0 and 9.4 μM, respectively. [I]/Ki ratios of efavirenz for trifluoperazine N-glucuronidation and propofol glucuronidation were 6.5 and 1.37, respectively. Efavirenz also moderately inhibited UGT1A1-mediated 17β-estradiol 3-glucuronidation, with a Ki value of 40.3 μM, but did not inhibit UGT1A6-mediated 1-naphthol glucuronidation. Those in vitro results suggest that efavirenz should be examined for potential pharmacokinetic drug interactions in vivo due to strong inhibition of UGT1A4 and UGT1A9.
Keywords: efavirenz; UDP-glucuronosyltransferase inhibition; human liver microsomes; drug-drug interaction efavirenz; UDP-glucuronosyltransferase inhibition; human liver microsomes; drug-drug interaction
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Ji, H.Y.; Lee, H.; Lim, S.R.; Kim, J.H.; Lee, H.S. Effect of Efavirenz on UDP-Glucuronosyltransferase 1A1, 1A4, 1A6, and 1A9 Activities in Human Liver Microsomes. Molecules 2012, 17, 851-860.

AMA Style

Ji HY, Lee H, Lim SR, Kim JH, Lee HS. Effect of Efavirenz on UDP-Glucuronosyltransferase 1A1, 1A4, 1A6, and 1A9 Activities in Human Liver Microsomes. Molecules. 2012; 17(1):851-860.

Chicago/Turabian Style

Ji, Hye Young; Lee, Hyeri; Lim, Sae Rom; Kim, Jeong Han; Lee, Hye Suk. 2012. "Effect of Efavirenz on UDP-Glucuronosyltransferase 1A1, 1A4, 1A6, and 1A9 Activities in Human Liver Microsomes." Molecules 17, no. 1: 851-860.



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