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Date of Award


Document Type

Thesis - Pacific Access Restricted

Degree Name

Master of Science (M.S.)


Pharmaceutical and Chemical Sciences

First Advisor

Miki Park

First Committee Member

William Chan

Second Committee Member

Liang Xue


Many people like to drink caffeinated beverages, such as coffee or tea, but are sensitive to effects of caffeine. Therefore, they either avoid drinking caffeinated beverages altogether, or they avoid drinking them close to bedtime to prevent caffeine from interfering with their sleep. Ruta Cleanse and Ruta Sleep are natural supplements containing rutaecarpine that are designed to speed up the removal of caffeine from the blood. The recommendation is to take two capsules (equivalent to 100 mg rutaecarpine), as needed, to reduce caffeine level. Customers have reported positive effects, when taken 30 minutes to 2 hours prior. However, there is no scientific data to show how soon Ruta Cleanse and Ruta Sleep need to be taken in order for it to work. Therefore, we tested in rats the effect of single dose after 3, 6, 12, 24 hour and 7 doses (once a day, for seven days) of oral 100 mg/kg rutaecarpine (in suspension) induction on caffeine pharmacokinetics upon 15 mg/kg intravenous bolus and 20 mg/kg oral caffeine doses. The MROD data showed that as early as 3 hours after oral rutaecarpine administration, CYP1A2 activity in the liver tissue is increased by almost 3-fold compared to control rats and highest activity (9-fold compared to control) is found in the liver of rats administered with daily oral dose of rutaecarpine, for seven days. A suspension form of 100 mg/kg orally administered rutaecarpine significantly decreases the oral systemic exposure and mean residence time of caffeine and its metabolites (paraxanthine, theophylline and theobromine), as early as 3 hours before oral caffeine administration. The oral caffeine bioavailability (F) decreases by about 50% for the 3, 6 and 12-hour, 70% for the 24 hour and 80% for the one week daily rutaecarpine treatment groups. Currently we do not know the mechanism by which rutaecarpine significantly decreases the F values of caffeine upon oral administration. The systemic exposure of caffeine and its metabolites are also decreased when caffeine is given intravenously, though the effect is less pronounced compared to when caffeine is given orally. Interestingly, rutaecarpine achieves this effect without achieving detectable plasma level (less than 10 ng/mL). However, since the target organ for rutaecarpine is the liver, rutaecarpine can still induce CYP1A2 enzyme in the liver (as indicated by MROD data), without having to get absorbed into blood circulation.





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