Membrane transporters in drug development.
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.
Giacomini
Kathleen M
KM
Huang
Shiew-Mei
SM
Tweedie
Donald J
DJ
Benet
Leslie Z
LZ
Brouwer
Kim L R
KL
Chu
Xiaoyan
X
Dahlin
Amber
A
Evers
Raymond
R
Fischer
Volker
V
Hillgren
Kathleen M
KM
Hoffmaster
Keith A
KA
Ishikawa
Toshihisa
T
Keppler
Dietrich
D
Kim
Richard B
RB
Lee
Caroline A
CA
Niemi
Mikko
M
Polli
Joseph W
JW
Sugiyama
Yuichi
Y
Swaan
Peter W
PW
Ware
Joseph A
JA
Wright
Stephen H
SH
Yee
Sook Wah
SW
Zamek-Gliszczynski
Maciej J
MJ
Zhang
Lei
L
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*
D026901:Membrane Transport Proteins; D055553:Prescription Drugs