Lopinavir: acute exposure inhibits P-glycoprotein; extended exposure induces P-glycoprotein

AIDS. 2003 May 2;17(7):1092-4. doi: 10.1097/01.aids.0000060380.78202.b5.

Abstract

The effect of lopinavir on P-glycoprotein-mediated rhodamine 123 efflux was studied in Caco-2 monolayer cells. Lopinavir is a potent inhibitor of Rh123 efflux in Caco-2 monolayers (IC50 1.7 microM). Chronic lopinavir exposure (72 h) in LS 180V cells reduced the content of intracellular Rh123 by approximately 50%, indicating increased efflux activity. In LS 180V cells, lopinavir induced P-glycoprotein immunoreactive protein (up to threefold) and messenger RNA levels in a concentration-dependent fashion.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • Anti-HIV Agents / pharmacology*
  • Blotting, Western
  • Caco-2 Cells
  • Dose-Response Relationship, Drug
  • Fluorescent Dyes / metabolism
  • HIV Protease Inhibitors / pharmacology*
  • Humans
  • Lopinavir
  • Pyrimidinones / pharmacology*
  • RNA, Messenger / metabolism
  • RNA, Viral / metabolism
  • Rhodamine 123 / antagonists & inhibitors
  • Time Factors

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anti-HIV Agents
  • Fluorescent Dyes
  • HIV Protease Inhibitors
  • Pyrimidinones
  • RNA, Messenger
  • RNA, Viral
  • Rhodamine 123
  • Lopinavir