title: Drug transporters in HIV Therapy.
abstract: Drug transporter proteins play a crucial role in drug disposition. The P-glycoprotein drug efflux transporter is a determinant of oral bioavailability and central nervous system (CNS) penetration of protease inhibitors (PIs), and may affect drug penetration to other tissue compartments that can serve as sanctuaries for HIV. Potent and selective inhibitors of P-glycoprotein can dramatically increase PI CNS penetration. Polymorphisms in the MDR1 gene regulating P-glycoprotein expression are associated with differences in drug disposition, with some data indicating that different genotypes are associated with differences in plasma PI levels and magnitudes of CD4+ cell count recovery under therapy. The activity of drug transporters in modulating antiretroviral drug effects and the potential for exploiting this activity to maximize therapeutic benefit and minimize drug toxicity are the subjects of ongoing study. In addition, inhibition of transporter proteins may increase the risk of hepatotoxicity and other adverse drug effects and is being investigated. This article summarizes a presentation given by Richard B. Kim, MD, at the March 2003 International AIDS Society-USA course in Atlanta.
authors.affiliation: Division of Clinical Pharmacology at Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Kim
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D001812:Blood-Brain Barrier / Q000502:physiology; D018791:CD4 Lymphocyte Count; D056486:Chemical and Drug Induced Liver Injury; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D024882:Drug Resistance, Viral / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D019450:Genes, MDR / Q000502:physiology*; D005838:Genotype; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D008107:Liver Diseases / Q000517:prevention & control; D026901:Membrane Transport Proteins / Q000502:physiology*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000502:physiology; D013997:Time Factors; D014018:Tissue Distribution / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D026901:Membrane Transport Proteins; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A