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Effects of uptake and efflux transporter inhibition on erythromycin breath test results.

Author(s): Frassetto LA, Poon S, Tsourounis C, Valera C, Benet LZ

Affiliation(s): Clinical Research Center and Department of Medicine, University of California at San Francisco, San Francisco, CA, USA. Leslie.Benet@ucsf.edu

Publication date & source: 2007-06, Clin Pharmacol Ther., 81(6):828-32. Epub 2007 Mar 14.

Publication type: Randomized Controlled Trial; Research Support, N.I.H., Extramural

The erythromycin breath test (EBT) is a standard test used to evaluate the extent of CYP3A4 activity. This study examines whether presumed changes in CYP3A4 activity are in fact related to inhibition of an uptake organic anion transporter using rifampin and inhibition of the efflux hepatic P-glycoprotein transporter using lansoprazole. Three EBT tests in healthy adults were conducted: EBT alone, with lansoprazole, and with rifampin. For all subjects, lansoprazole treatment increased respiratory (14)C excretion by +0.25+/-0.51 met/h (P=0.07) and rifampin decreased (14)C excretion by -0.44+/-0.40 met/h (P<0.001) compared with baseline. Comparing lansoprazole to rifampin, (14)C excretion increased by +0.69+/-0.50 met/h (P<0.001). Only women had significant changes after drug infusion: (14)C excretion after rifampin -0.40+/-0.36 met/h (P=0.018) and +0.47+/-0.44 met/h (P=0.018) after lansoprazole. Relying on EBT without considering transporter interactions can lead to errors in interpreting the degree of CYP3A4 metabolism.

Page last updated: 2007-08-04

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