title: The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective.
abstract: 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.
authors.affiliation: Wyeth, Collegeville, Pennsylvania, USA.
authors.forename: Thorir D
authors.initials: TD
authors.lastname: Bjornsson
authors.forename: John T
authors.initials: JT
authors.lastname: Callaghan
authors.forename: Heidi J
authors.initials: HJ
authors.lastname: Einolf
authors.forename: Volker
authors.initials: V
authors.lastname: Fischer
authors.forename: Lawrence
authors.initials: L
authors.lastname: Gan
authors.forename: Scott
authors.initials: S
authors.lastname: Grimm
authors.forename: John
authors.initials: J
authors.lastname: Kao
authors.forename: S Peter
authors.initials: SP
authors.lastname: King
authors.forename: Gerald
authors.initials: G
authors.lastname: Miwa
authors.forename: Lan
authors.initials: L
authors.lastname: Ni
authors.forename: Gondi
authors.initials: G
authors.lastname: Kumar
authors.forename: James
authors.initials: J
authors.lastname: McLeod
authors.forename: R Scott
authors.initials: RS
authors.lastname: Obach
authors.forename: Stanley
authors.initials: S
authors.lastname: Roberts
authors.forename: Amy
authors.initials: A
authors.lastname: Roe
authors.forename: Anita
authors.initials: A
authors.lastname: Shah
authors.forename: Fred
authors.initials: F
authors.lastname: Snikeris
authors.forename: John T
authors.initials: JT
authors.lastname: Sullivan
authors.forename: Donald
authors.initials: D
authors.lastname: Tweedie
authors.forename: Jose M
authors.initials: JM
authors.lastname: Vega
authors.forename: John
authors.initials: J
authors.lastname: Walsh
authors.forename: Steven A
authors.initials: SA
authors.lastname: Wrighton
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000145:classification / Q000378:metabolism; D004345:Drug Industry; D004347:Drug Interactions; D012107:Research Design
chemical_list: D003577:Cytochrome P-450 Enzyme System