title: In vivo drug-drug interaction studies--a survey of all new molecular entities approved from 1987 to 1997.
abstract: Ninety-eight new molecular entities applications approved between 1987 to 1991 (period I) and 193 applications for new molecular entities between 1992 to 1997 (period II) were surveyed for drug-drug interaction studies. In period I (used as a comparator), 32 applications contained drug-drug interaction studies for a total of 117 studies. In period II, 106 applications reported drug-drug interaction studies, and the number of studies per new molecular entity ranged from 0 to 15. Most studies (77%) were performed in healthy subjects, with 44% using crossover designs, 7% using parallel designs, and the remaining using fixed sequence designs. The most common dosing scheme for new molecular entities/interacting drug was multiple dose (47%), whereas single dose/multiple dose was used in 31% of studies, and single dose/single dose was used in 18% of studies. Of the 540 drug-drug interaction studies submitted in period II, 80 (15%) resulted in clinically significant labeling statements. Submissions for new molecular entities to the Center for Drug Evaluation and Research divisions most likely to include drug-drug interaction studies were neuropharmacology, cardiorenal, antiviral, and antiinfective drugs. Some drug classes such as oncology drug products and radioimaging products were least likely to include drug-drug interaction studies in their submissions. We conclude that the use of drug-drug interaction studies in the drug development process has increased between the two periods.
authors.affiliation: Office of Clinical Pharmacology and Biopharmaceutics, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD 20857, USA. marroump@cder.fda.gov
authors.forename: P J
authors.initials: PJ
authors.lastname: Marroum
authors.forename: R S
authors.initials: RS
authors.lastname: Uppoor
authors.forename: T
authors.initials: T
authors.lastname: Parmelee
authors.forename: F
authors.initials: F
authors.lastname: Ajayi
authors.forename: A
authors.initials: A
authors.lastname: Burnett
authors.forename: R
authors.initials: R
authors.lastname: Yuan
authors.forename: R
authors.initials: R
authors.lastname: Svadjian
authors.forename: L J
authors.initials: LJ
authors.lastname: Lesko
authors.forename: J D
authors.initials: JD
authors.lastname: Balian
mesh_terms: D001702:Biopharmaceutics; D002986:Clinical Trials as Topic; D018592:Cross-Over Studies; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D006801:Humans; D014481:United States; D014486:United States Food and Drug Administration