Pj. Marroum et al., In vivo drug-drug interaction studies - A survey of all new molecular entities approved from 1987 to 1997, CLIN PHARM, 68(3), 2000, pp. 280-285
Ninety-eight new molecular entities applications approved between 1987 to 1
991 (period I) and 193 applications for new molecular entities between 1992
to 1997 (period II) were surveyed for drug-drug interaction studies. In pe
riod I (used as a comparator), 32 applications contained drug-drug interact
ion studies for a total of 117 studies. In period II, 106 applications repo
rted drug-drug interaction studies, and the number of studies per new molec
ular entity ranged from 0 to 15. Most studies (77%) were performed in healt
hy subjects, with 44% using crossover designs, 7% using parallel designs, a
nd the remaining using fixed sequence designs, The most common dosing schem
e for new molecular entities/interacting drug was multiple dose (47%), wher
eas single dose/multiple dose was used in 31% of studies, and single dose/s
ingle dose was used in 18% of studies. Of the 540 drug-drug interaction stu
dies submitted in period II, 80 (15%) resulted in clinically significant la
beling statements, Submissions for new molecular entities to the Center for
Drug Evaluation and Research divisions most likely to include drug-drug in
teraction studies were neuropharmacology, cardiorenal, antiviral, and antii
nfective drugs, Some drug classes such as oncology drug products and radioi
maging products were least likely to include drug-drug interaction studies
in their submissions. We conclude that the use of drug-drug interaction stu
dies in the drug development process has increased between the two periods.