title: Transport of HIV protease inhibitors through the blood-brain barrier and interactions with the efflux proteins, P-glycoprotein and multidrug resistance proteins.
abstract: HIV protease inhibitors (HPIs) have limited penetration into the brain. This poor transport through the blood-brain barrier is mainly due to active efflux by proteins such as P-glycoprotein (P-gp) preventing drugs from clearing the brain of the virus. The present paper focuses on cerebral uptake of HPIs and interactions between HPIs and efflux proteins, either as substrates or modulators. Most of the studies described HPIs as P-gp substrates. Studies are more controversial when investigating HPIs as inhibitors of P-gp. HPIs seem to be able to inhibit efflux proteins of in vitro cell models but with limited consequences in vivo. Moreover, after repeated administrations of HPIs, most of them are also able to induce the expression and functionality of P-gp. For these reasons, certain combinations of HPIs may not efficiently increase brain uptake of HPIs as would combinations of more potent efflux inhibitors.
authors.affiliation: Pharmacie Clinique, Université Paris XI, Châtenay-Malabry, France. francois.gimenez@nck.ap-hop-paris.fr
authors.forename: François
authors.initials: F
authors.lastname: Gimenez
authors.forename: Christine
authors.initials: C
authors.lastname: Fernandez
authors.forename: Aloïse
authors.initials: A
authors.lastname: Mabondzo
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000378:metabolism; D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D011485:Protein Binding
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017320:HIV Protease Inhibitors