Study of Ultra‐Sensitive AMS Method to Identify Drug–Drug Interactions between Ciprofloxacin and Microdose 14C‐Caffeine

Identifying drug–drug interactions, potentially affecting efficacy and safety of each drug is essential for drug development. Microdose, administration of a drug at less than 100 μg or 1/100 of its therapeutic dose, is a promising method to safely test drugs during development. This paper examines drug–drug interactions between therapeutic doses of ciprofloxacin and trace amounts of 14C‐ caffeine for microdosing in mice using AMS for analysis. The pharmacokinetic (PK) parameters for caffeine with and without administration of ciprofloxacin did not show any change in Tmax. However, the values of T1/2, Cmax, and AUCinf with administration of ciprofloxacin increased by 57, 22, and 42%, respectively. This is in agreement with previous studies that used full prescription doses. It is shown here that microdose techniques combined with AMS measurements can be used for accurate prediction of drug–drug interactions while conducting relatively safe, small dose studies.