Lopinavir: acute exposure inhibits P-glycoprotein; extended exposure induces P-glycoprotein.
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.
Vishnuvardhan
Daesety
D
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA.
Moltke
Lisa L
LL
Richert
Clemens
C
Greenblatt
David J
DJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D019380:Anti-HIV Agents / Q000494:pharmacology*; D015153:Blotting, Western; D018938:Caco-2 Cells; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D061466:Lopinavir; D011744:Pyrimidinones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D020112:Rhodamine 123 / Q000037:antagonists & inhibitors; D013997:Time Factors
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019380:Anti-HIV Agents; D005456:Fluorescent Dyes; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D012333:RNA, Messenger; D012367:RNA, Viral; D020112:Rhodamine 123; D061466:Lopinavir