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Effects of Uptake and Efflux Transporter Inhibition on Erythromycin Breath Test Results
Author(s) -
Frassetto L A,
Poon S,
Tsourounis C,
Valera C,
Benet L Z
Publication year - 2007
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100148
Subject(s) - lansoprazole , cyp3a4 , pharmacology , transporter , excretion , chemistry , erythromycin , p glycoprotein , efflux , pharmacokinetics , breath test , medicine , metabolism , antibiotics , biochemistry , cytochrome p450 , omeprazole , multiple drug resistance , gene , helicobacter pylori
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. Clinical Pharmacology & Therapeutics (2007) 81 , 828–832. doi: 10.1038/sj.clpt.6100148 ; published online 14 March 2007