Comparative Effects of Azithromycin, Telithromycin and Levofloxacin on Drug Metabolizing Enzymes
Status:
Completed
Trial end date:
2005-06-01
Target enrollment:
Participant gender:
Summary
Studies have previously shown that a broad drug interaction screening can be performed using
enzyme specific probes such as oral caffeine for CYP1A2, N-acetyltrasferase-2 (NAT-2), and
xanthine oxidase (XO), warfarin plus vitamin K for CYP2C9, omeprazole for CYP 2C19,
dextromethorphan for CYP2D6, and midazolam for CYP3A4/5. This combination of probes has been
validated in the Cooperstown 5+1 Cocktail (5+1).1 The use of the 5+1 cocktail provides
information on the drug metabolizing enzymes that metabolize 90% of hepatically eliminated
drugs for a fraction of the costs of the individual studies. Using a cocktail of biomarkers
reduces the overall cost of drug interaction screening. The purpose of this study is to
evaluate the effects of three Food and Drug Administration (FDA) approved oral antibiotics
(azithromycin, telithromycin, and levofloxacin) on metabolism of other medications when taken
together. This will be determined by the measuring the activity of drug metabolizing enzymes
following administration of certain drug probes (caffeine, dextromethorphan, omeprazole,
midazolam, and warfarin with vitamin K). A total of 16 subjects will complete four phases of
the study: 1) Cooperstown 5+1 alone, 2) Azithromycin plus Cooperstown 5+1, 3) Telithromycin
plus Cooperstown 5+1, and 4) Levofloxacin plus Cooperstown 5+1.