Study of Ultra-Sensitive AMS Method to Identify Drug-Drug Interactions between Ciprofloxacin and Microdose ~(14)C-Caffeine

摘要

Identifying drug-drug interactions, potentially affecting efficacy and safety of each drag is essential for drag development. Microdose, administration of a drag at less than 100 μg or 1/100 of its therapeutic dose, is a promising method to safely test drags during development. This paper examines drag-drug interactions between therapeutic doses of ciprofloxacin and trace amounts of C- 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 T_(max). However, the values of T_(1/2), C_(max), and AUC_(inf) 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 drag-drug interactions while conducting relatively safe, small dose studies.