RT Journal Article
SR Electronic
T1 In Vitro and in Vivo Induction of Cytochrome P450: A Survey of the Current Practices and Recommendations: A Pharmaceutical Research and Manufacturers of America Perspective
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1339
OP 1354
DO 10.1124/dmd.109.027029
VO 37
IS 7
A1 Chu, Valeria
A1 Einolf, Heidi J.
A1 Evers, Raymond
A1 Kumar, Gondi
A1 Moore, David
A1 Ripp, Sharon
A1 Silva, Jose
A1 Sinha, Vikram
A1 Sinz, Michael
A1 Skerjanec, Andrej
YR 2009
UL http://dmd.aspetjournals.org/content/37/7/1339.abstract
AB Cytochrome P450 (P450) induction is one of the factors that can affect the pharmacokinetics of a drug molecule upon multiple dosing, and it can result in pharmacokinetic drug-drug interactions with coadministered drugs causing potential therapeutic failures. In recent years, various in vitro assays have been developed and used routinely to assess the potential for drug-drug interactions due to P450 induction. There is a desire from the pharmaceutical industry and regulatory agencies to harmonize assay methodologies, data interpretation, and the design of clinical drug-drug interaction studies. In this article, a team of 10 scientists from nine Pharmaceutical Research and Manufacturers of America (PhRMA) member companies conducted an anonymous survey among PhRMA companies to query current practices with regards to the conduct of in vitro induction assays, data interpretation, and clinical induction study practices. The results of the survey are presented in this article, along with reviews of current methodologies of in vitro assays and in vivo studies, including modeling efforts in this area. A consensus recommendation regarding common practices for the conduct of P450 induction studies is included.