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In our PK study where we treated a small number of nonhuman primates
different age groups with phenytoin at a dose of 30 mg/kg for 2 weeks,
phenytoin Cmax and AUC at Tmax of 4 hours were elevated in the 6-month
infants compared to the adult animals although the plasma concentration
levels in the infants eventually declined to near adult levels by the
hour. These findings did not seem to be consistent with the mean CYP2C9
Vmax/Km and Vmax values which appeared to be highest in the infants
to the other age groups. Could there be possible reasons to explain this
Note: Vmax/Km and Vmax values of CYP2C19 (the other enzyme also
be involved in phenytoin metabolism) were lower in all phenytoin-treated
animals (feedback inhibition?). As expected, phenytoin induced CYP3A4 in
terms of Vmax.
I'll be glad to receive your comments/explanations.
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