Effects of Uptake and Efflux Transporter Inhibition on Erythromycin Breath Test Results

Abstract

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 Ce xcretion byþ 0.2570.51 met/h (P ¼ 0.07) and rifampin decreased 14 Ce xcretion by � 0.4470.40 met/h (Po0.001) compared with baseline. Comparing lansoprazole to rifampin, 14C excretion increased by þ 0.6970.50 met/h (Po0.001). Only women had significant changes after drug infusion: 14C excretion after rifampin -0.4070.36 met/h (P ¼ 0.018) and þ 0.4770.44 met/h (P ¼ 0.018) after lansoprazole. Relying on EBT without considering transporter interactions can lead to errors in interpreting the degree of CYP3A4 metabolism. The cytochrome P450 (CYP450) family is the major metabolic enzyme system in the liver. CYP3A4 alone is responsible for the metabolism of more than 50% of all drugs sold in the US that are metabolized by the P450 system.1