New era in drug interaction evaluation: US Food and Drug Administration update on CYP enzymes, transporters, and the guidance process.
Predicting clinically significant drug interactions during drug development is a challenge for the pharmaceutical industry and regulatory agencies. Since the publication of the US Food and Drug Administration's (FDA's) first in vitro and in vivo drug interaction guidance documents in 1997 and 1999, researchers and clinicians have gained a better understanding of drug interactions. This knowledge has enabled the FDA and the industry to progress and begin to overcome these challenges. The FDA has continued its efforts to evaluate methodologies to study drug interactions and communicate recommendations regarding the conduct of drug interaction studies, particularly for CYP-based and transporter-based drug interactions, to the pharmaceutical industry. A drug interaction Web site was established to document the FDA's current understanding of drug interactions (http://www.fda.gov/cder/drug/drugInteractions/default.htm). This report provides an overview of the evolution of the drug interaction guidances, includes a synopsis of the steps taken by the FDA to revise the original drug interaction guidance documents, and summarizes and highlights updated sections in the current guidance document, Drug Interaction Studies-Study Design, Data Analysis, and Implications for Dosing and Labeling.
Huang
Shiew-Mei
SM
Office of Clinical Pharmacology, CDER, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
Strong
John M
JM
Zhang
Lei
L
Reynolds
Kellie S
KS
Nallani
Srikanth
S
Temple
Robert
R
Abraham
Sophia
S
Habet
Sayed Al
SA
Baweja
Raman K
RK
Burckart
Gilbert J
GJ
Chung
Sang
S
Colangelo
Philip
P
Frucht
David
D
Green
Martin D
MD
Hepp
Paul
P
Karnaukhova
Elena
E
Ko
Hon-Sum
HS
Lee
Jang-Ik
JI
Marroum
Patrick J
PJ
Norden
Janet M
JM
Qiu
Wei
W
Rahman
Atiqur
A
Sobel
Solomon
S
Stifano
Toni
T
Thummel
Kenneth
K
Wei
Xiao-Xiong
XX
Yasuda
Sally
S
Zheng
Jenny H
JH
Zhao
Hong
H
Lesko
Lawrence J
LJ
D001692:Biological Transport / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D015195:Drug Design; D004347:Drug Interactions; D017408:Guidelines as Topic; D006801:Humans; D014481:United States; D014486:United States Food and Drug Administration
D003577:Cytochrome P-450 Enzyme System