PT  - JOURNAL ARTICLE
AU  - Thorir D. Bjornsson
AU  - John T. Callaghan
AU  - Heidi J. Einolf
AU  - Volker Fischer
AU  - Lawrence Gan
AU  - Scott Grimm
AU  - John Kao
AU  - S. Peter King
AU  - Gerald Miwa
AU  - Lan Ni
AU  - Gondi Kumar
AU  - James McLeod
AU  - R. Scott Obach
AU  - Stanley Roberts
AU  - Amy Roe
AU  - Anita Shah
AU  - Fred Snikeris
AU  - John T. Sullivan
AU  - Donald Tweedie
AU  - Jose M. Vega
AU  - John Walsh
AU  - Steven A. Wrighton
TI  - THE CONDUCT OF IN VITRO AND IN VIVO DRUG-DRUG INTERACTION STUDIES: A PHARMACEUTICAL RESEARCH AND MANUFACTURERS OF AMERICA (PhRMA) PERSPECTIVE
AID  - 10.1124/dmd.31.7.815
DP  - 2003 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 815--832
VI  - 31
IP  - 7
4099  - http://dmd.aspetjournals.org/content/31/7/815.short
4100  - http://dmd.aspetjournals.org/content/31/7/815.full
SO  - Drug Metab Dispos2003 Jul 01; 31
AB  - Current regulatory guidances do not address specific study designs for in vitro and in vivo drug-drug interaction studies. There is a common desire by regulatory authorities and by industry sponsors to harmonize approaches, to allow for a better assessment of the significance of findings across different studies and drugs. There is also a growing consensus for the standardization of cytochrome P450 (P450) probe substrates, inhibitors and inducers and for the development of classification systems to improve the communication of risk to health care providers and to patients. While existing guidances cover mainly P450-mediated drug interactions, the importance of other mechanisms, such as transporters, has been recognized more recently, and should also be addressed. This article was prepared by the Pharmaceutical Research and Manufacturers of America (PhRMA) Drug Metabolism and Clinical Pharmacology Technical Working Groups and represents the current industry position. The intent is to define a minimal best practice for in vitro and in vivo pharmacokinetic drug-drug interaction studies targeted to development (not discovery support) and to define a data package that can be expected by regulatory agencies in compound registration dossiers. The American Society for Pharmacology and Experimental Therapeutics