title: Membrane transporters in drug development.
abstract: Membrane transporters can be major determinants of the pharmacokinetic, safety and efficacy profiles of drugs. This presents several key questions for drug development, including which transporters are clinically important in drug absorption and disposition, and which in vitro methods are suitable for studying drug interactions with these transporters. In addition, what criteria should trigger follow-up clinical studies, and which clinical studies should be conducted if needed. In this article, we provide the recommendations of the International Transporter Consortium on these issues, and present decision trees that are intended to help guide clinical studies on the currently recognized most important drug transporter interactions. The recommendations are generally intended to support clinical development and filing of a new drug application. Overall, it is advised that the timing of transporter investigations should be driven by efficacy, safety and clinical trial enrolment questions (for example, exclusion and inclusion criteria), as well as a need for further understanding of the absorption, distribution, metabolism and excretion properties of the drug molecule, and information required for drug labelling.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Giacomini
authors.forename: Shiew-Mei
authors.initials: SM
authors.lastname: Huang
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Tweedie
authors.forename: Leslie Z
authors.initials: LZ
authors.lastname: Benet
authors.forename: Kim L R
authors.initials: KL
authors.lastname: Brouwer
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chu
authors.forename: Amber
authors.initials: A
authors.lastname: Dahlin
authors.forename: Raymond
authors.initials: R
authors.lastname: Evers
authors.forename: Volker
authors.initials: V
authors.lastname: Fischer
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Hillgren
authors.forename: Keith A
authors.initials: KA
authors.lastname: Hoffmaster
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Dietrich
authors.initials: D
authors.lastname: Keppler
authors.forename: Richard B
authors.initials: RB
authors.lastname: Kim
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Lee
authors.forename: Mikko
authors.initials: M
authors.lastname: Niemi
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Polli
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Peter W
authors.initials: PW
authors.lastname: Swaan
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Ware
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Wright
authors.forename: Sook Wah
authors.initials: SW
authors.lastname: Yee
authors.forename: Maciej J
authors.initials: MJ
authors.lastname: Zamek-Gliszczynski
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003198:Computer Simulation; D003663:Decision Trees; D017277:Drug Approval; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004347:Drug Interactions; D006801:Humans; D026901:Membrane Transport Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D055553:Prescription Drugs / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D026901:Membrane Transport Proteins; D055553:Prescription Drugs