ITC Commentary on the Prediction of Digoxin Clinical Drug-Drug Interactions from In Vitro Transporter Assays

被引：25

作者：

Lee, C. A. ^{[1
]}

Kalvass, J. C. ^{[2
]}

Galetin, A. ^{[3
]}

Zamek-Gliszczynski, M. J. ^{[4
]}

机构：

[1] QPS DMPK Hepat Biosci, Res Triangle Pk, NC USA

[2] AbbVie, Drug Metab & Pharmacokinet, N Chicago, IL USA

[3] Univ Manchester, Ctr Appl Pharmacokinet Res, Manchester Pharm Sch, Manchester, Lancs, England

[4] GlaxoSmithKline, Drug Metab & Pharmacokinet, Res Triangle Pk, NC 27709 USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2014年 / 96卷 / 03期

关键词：

P-GLYCOPROTEIN; PARAMETER; CELLS;

D O I：

10.1038/clpt.2014.94

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The"P-glycoprotein"IC50 working group reported an 18- to 796-fold interlaboratory range in digoxin transport IC50 (inhibitor concentration achieving 50% of maximal inhibition), raising concerns about the predictability of clinical transporter-based drug-drug interactions (DDIs) from in vitro data. This Commentary describes complexities of digoxin transport, which involve both uptake and efflux processes. We caution against attributing digoxin transport IC50 specifically to P-glycoprotein (P-gp) or extending this composite uptake/efflux IC50 variability to individual transporters. Clinical digoxin interaction studies should be interpreted as evaluation of digoxin safety, not P-gp DDIs.

引用

页码：298 / 301

页数：4

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