title: Why clinical modulation of efflux transport at the human blood-brain barrier is unlikely: the ITC evidence-based position.
abstract: Drug interactions due to efflux transport inhibition at the blood-brain barrier (BBB) have been receiving increasing scrutiny because of the theoretical possibility of adverse central nervous system (CNS) effects identified in preclinical studies. In this review, evidence from pharmacokinetic, pharmacodynamic, imaging, pharmacogenetic, and pharmacovigilance studies, along with drug safety reports, is presented supporting a low probability of modulating transporters at the human BBB by currently marketed drugs.
authors.affiliation: Experimental Kinetics and Analysis, Abbott Laboratories, Abbott Park, Illinois, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Kalvass
authors.forename: J W
authors.initials: JW
authors.lastname: Polli
authors.forename: D L
authors.initials: DL
authors.lastname: Bourdet
authors.forename: B
authors.initials: B
authors.lastname: Feng
authors.forename: S-M
authors.initials: SM
authors.lastname: Huang
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: Q R
authors.initials: QR
authors.lastname: Smith
authors.forename: L K
authors.initials: LK
authors.lastname: Zhang
authors.forename: M J
authors.initials: MJ
authors.lastname: Zamek-Gliszczynski
mesh_terms: D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000378:metabolism*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D004364:Pharmaceutical Preparations; D010599:Pharmacokinetics
chemical_list: D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations