Predicting Drug Candidate Victims of Drug-Drug Interactions, using Microdosing
Clinical Pharmacokinetics February 16, 2012 Marie Croft, Brendan J. Keely, Ian D. Morris et al. 42 citations
A crossover study in healthy male volunteers tested whether microdosing (25 μg each of midazolam, tolbutamide, caffeine, and fexofenadine) can detect drug-drug interactions. After administering pharmacological doses of ketoconazole (400 mg) and fluvoxamine (100 mg) to inhibit key metabolic enzymes and transporters, the microdosed compounds showed significant pharmacokinetic changes: area under the curve increased 12.8-fold for midazolam, 8.1-fold for caffeine, and 3.2-fold for fexofenadine (all p < 0.01), and 1.8-fold (not significant) for tolbutamide. These changes matched those reported in conventional drug-drug interaction studies, demonstrating microdosing's utility for assessing whether development drugs are victims of interactions.