Inhibitory effect of human immunodeficiency virus protease inhibitors on multidrug resistance transporter P-glycoproteins

Biol Pharm Bull. 2000 Dec;23(12):1528-31. doi: 10.1248/bpb.23.1528.


The objective of this study was to determine whether human immunodeficiency virus (HIV) protease inhibitors (saquinavir, ritonavir and nelfinavir) interact with other HIV protease inhibitors and/or HIV reverse transcriptase inhibitors (zidovudine, didanosine, lamivudine, zalcitabine and sanilvudine). We measured transport of nelfinavir, an HIV protease inhibitor which is known as a substrate for the multidrug resistance transporter P-glycoprotein (P-gp), in an epithelial monolayer model and Ki for P-gp of some drugs by a calcein flux assay. Transport in a basal to apical direction was 2-fold greater than apical to basal flux for nelfinavir, Ki for P-gp of a potent P-gp inhibitor cyclosporin A was 1.09 microM and those of ritonavir and nelfinavir were 111 microM and 28.6 microM, whereas all HIV reverse transcriptase inhibitors gave high K1 values. These data show that nelfinavir, which is a substrate for P-gp, inhibits a P-gp function as a drug efflux pump and that HIV reverse transcriptase inhibitors do not inhibit P-gp.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Anti-HIV Agents / pharmacokinetics
  • Anti-HIV Agents / pharmacology
  • Biological Transport / drug effects
  • Drug Interactions
  • Fluoresceins / pharmacokinetics
  • Fluorescent Dyes / pharmacokinetics
  • HIV Protease Inhibitors / pharmacokinetics
  • HIV Protease Inhibitors / pharmacology*
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • Humans
  • Kinetics
  • LLC-PK1 Cells / drug effects
  • LLC-PK1 Cells / metabolism
  • Nelfinavir / pharmacokinetics
  • Reverse Transcriptase Inhibitors / pharmacology
  • Ritonavir / pharmacokinetics
  • Ritonavir / pharmacology
  • Swine
  • Transfection


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anti-HIV Agents
  • Fluoresceins
  • Fluorescent Dyes
  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors
  • calcein AM
  • HIV Reverse Transcriptase
  • Nelfinavir
  • Ritonavir