1. ¹Clinical Research Center and Department of Medicine, University of California at San Francisco, San Francisco, CA, USA
2. ²Department of Clinical Pharmacy, University of California at San Francisco, San Francisco, CA, USA
3. ³Department of Biopharmaceutical Sciences, University of California at San Francisco, San Francisco, CA, USA

Correspondence: LZ Benet, (Leslie.Benet@ucsf.edu)

Received 18 October 2006; Accepted 21 January 2007; Published online 14 March 2007.

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 ¹⁴C excretion by +0.250.51 met/h (P=0.07) and rifampin decreased ¹⁴C excretion by -0.440.40 met/h (P<0.001) compared with baseline. Comparing lansoprazole to rifampin, ¹⁴C excretion increased by +0.690.50 met/h (P<0.001). Only women had significant changes after drug infusion: ¹⁴C excretion after rifampin –0.400.36 met/h (P=0.018) and +0.470.44 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.