Use of microdosing to predict pharmacokinetics at the therapeutic dose: Experience with 5 drugs
Clinical Pharmacology & Therapeutics September 1, 2006 Graham Lappin, W. Kuhnz, R. Jochemsen et al. 242 citations
A volunteer trial compared how five drugs—warfarin, ZK253, diazepam, midazolam, and erythromycin—are handled by the body when given as a microdose (100 micrograms) versus a standard therapeutic dose. For diazepam, midazolam, and ZK253, the microdose closely matched the therapeutic dose in key measures such as half-life, clearance, volume of distribution, and oral bioavailability. Warfarin's clearance was reasonably predicted from the microdose, but its volume of distribution differed, likely due to high-affinity, low-capacity tissue binding. The oral microdose of erythromycin produced no detectable blood levels, possibly because stomach acid destroyed it. Overall, microdosing can help select promising drug candidates early, if used appropriately.