Background: Clobazam (CLBZ) metabolized primarily by Cytochrome P-450 isoenzyme CYP3A4 than
with CYP2C19, Whereas Levetiracetam (LEV) is metabolized by hydrolysis of the acetamide group. Few CYP enzymes
are inhibited by Proton Pump Inhibitors (PPIs) Pantoprazole, Esomeprazole, and Rabeprazole in different
extents that could affect drug concentrations in blood. The aim of the present study was to evaluate the effect of these
PPIs on the plasma concentrations of LEV and CLBZ.
Methods: Blood samples from 542 patients were included out of which 343 were male and 199 were female patients
and were categorized as control and test. Plasma samples analyzed using an HPLC-UV method. Plasma concentrations
were measured and compared to those treated and those not treated with PPIs. One way ANOVA and games
Howell post hoc test used by SPSS 20 software.
Results: CLBZ concentrations were significantly 10 folds higher in patients treated with Pantoprazole (P=0.000) and
07 folds higher in patients treated with Esmoprazole and Rabeprazole (P=0.00). Whereas plasma concentration of
LEV control group has no statistical and significant difference when compared to pantoprazole (P=0.546) and with
rabeprazole and esomeprazole was P=0.999.
Conclusion: The effect of comedication with PPIs on the plasma concentration of clobazam is more pronounced for
pantoprazole to a greater extent when compared to esomeprazole and rabeprazole. When pantoprazole is used in
combination with clobazam, dose reduction of clobazam should be considered, or significance of PPIs is seen to
avoid adverse effects.