Comparative study on the para-metabolic oxidation of phenytoin and decadeuteriophenytoin.

The in-vivo metabolic conversion of equal mixture of phenytoin and decadeuteriophenytoin to the para-hydroxy metabolite in rat was investigated in order to verify a possible role of an insertion or abstraction mechanisms in the hydroxylation process. Determination of kH/k2H values of urine samples at 2 h intervals for 24 h indicated that there was no isotope effect during in-vivo para-hydroxylation of phenytoin. This gives evidence of the arene oxide intermediacy possibly being the sole pathway for para-hydroxylation of phenytoin.