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

被引：44
作者：
Frassetto, L. A.
Poon, S.
Tsourounis, C.
Valera, C.
Benet, L. Z. [1 ]
机构：
[1] Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Clin Res Ctr, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA
来源：
CLINICAL PHARMACOLOGY & THERAPEUTICS | 2007年 / 81卷 / 06期
关键词：
D O I：
10.1038/sj.clpt.6100148
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
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 C-14 excretion by +0.257 +/- 0.51met/ h (P=0.07) and rifampin decreased C-14 excretion by - 0.447 +/- 0.40 met/h ( P < 0.001) compared with baseline. Comparing lansoprazole to rifampin, C-14 excretion increased by -0.697 +/- 0.50met/h ( P < 0.001). Only women had significant changes after drug infusion: C-14 excretion after rifampin -0.407 +/- 0.36met/h ( P < 0.018) and +0.47 +/- 0.44met/h ( P=0.018) after lansoprazole. Relying on EBT without considering transporter interactions can lead to errors in interpreting the degree of CYP3A4 metabolism.
引用
收藏
页码：828 / 832
页数：5
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