title: Drug and xenobiotic biotransformation in the blood-brain barrier: a neglected issue.
abstract: Drug biotransformation is a crucial mechanism for facilitating the elimination of chemicals from the organism and for decreasing their pharmacological activity. Published evidence suggests that brain drug metabolism may play a role in the development of adverse drug reactions and in the clinical response to drugs and xenobiotics. The blood-brain barrier (BBB) has been regarded mainly as a physical barrier for drugs and xenobiotics, and little attention has been paid to the BBB as a drug-metabolizing barrier. The presence of drug-metabolizing enzymes in the BBB is likely to have functional implications because local metabolism may inactivate drugs or may modify the drug's ability to cross the BBB, thus modifying drug response and the risk of developing adverse drug reactions. In this perspective paper, we discuss the expression of relevant xenobiotic metabolizing enzymes in the brain and in the BBB, and we cover current advances and future directions on the potential role of these BBB drug-metabolizing enzymes as modifiers of drug response.
authors.affiliation: Department of Pharmacology, University of Extremadura Cáceres, Spain ; ISCIII Research Network of Adverse Reactions to Allergens and Drugs Madrid, Spain.
authors.forename: José A G
authors.initials: JA
authors.lastname: Agúndez
authors.affiliation: Section of Neurology, Hospital Universitario del Sureste Madrid, Spain.
authors.forename: Félix J
authors.initials: FJ
authors.lastname: Jiménez-Jiménez
authors.affiliation: Section of Neurology, Hospital Universitario del Sureste Madrid, Spain.
authors.forename: Hortensia
authors.initials: H
authors.lastname: Alonso-Navarro
authors.affiliation: ISCIII Research Network of Adverse Reactions to Allergens and Drugs Madrid, Spain ; Department of Biochemistry, Molecular Biology and Genetics, University of Extremadura Cáceres, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: García-Martín
keywords: CNS drug; blood–brain barrier; drug metabolizing enzymes; drug response; expression profiling