Effect of esomeprazole on pharmacokinetics of phenytoin in rabbits.
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Date
2012-10
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Abstract
Esomeprazole is commonly prescribed proton pump inhibitor for
gastritis and peptic ulcer disease. Most of the time in clinical practice,
phenytoin and esomeprazole are prescribed for patients of generalized
seizures with concomitant peptic ulcer. Hence there are chances of drugdrug
interaction because of modulations of isoenzymes CYP2C9 and
CYP2C19, are involved in metabolism of phenytoin and esomeprazole. But
it is important to maintain the therapeutic level of phenytoin in plasma for
effective seizures control. So, the aim of the study was to determine the
effect of esomeprazole on the pharmacokinetics of phenytoin in rabbits. In
a parallel design study, phenytoin, 30 mg/kg/day per oral was given daily
for 14 days. On day 15, blood samples were taken at various time intervals
between 0-24 hours. In esomeprazole-phenytoin group, phenytoin was
administered for seven days as mentioned earlier and from day 8th onward,
esomeprazole 2.8 mg/kg along with phenytoin 30 mg/kg/day was administered
till 14th days and blood samples were drawn as above on 15th day. Plasma
phenytoin levels were assayed by HPLC and pharmacokinetic parameters
were calculated. In esomeprazole-phenytoin group, there was a significant
increase of t½el than phenytoin alone group and significant increase in
AUC0-24 was also observed in the esomeprazole and phenytoin treated
group. These results suggest that esomeprazole alters the pharmacokinetics
of phenytoin. Confirmation of these results in further clinical studies will
warrant changes in phenytoin dose or frequency when esomeprazole is
co-administered.
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Keywords
phenytoin, esomeprazole, rabbits, pharmacokinetics
Citation
Medhi B, Prakash A, Joshi Rupa, Byrav D S Prasad. Effect of esomeprazole on pharmacokinetics of phenytoin in rabbits. Indian Journal of Physiology and Pharmacology. 2012 Oct-Dec; 56(4): 382-387.