Stereoselective mephobarbital hydroxylation cosegregates with mephenytoin hydroxylation

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Abstract
The 8-hour urinary recovery of 4-hydroxy-mephobarbital has been measured after oral administration of racemic mephobarbital (90 mg) in 17 extensive (EM) and six poor (PM) metabolizer phenotypes of mephenytoin. The recovery of this metabolite was measurable in every EM and ranged from 2.5% to 48% (10.9% .+-. 1.9% of dose), but was not detected in any PM (< 1% of dose). In EMs, the 8-hour urine recovery of 4-OH-mephobarbital after mephobarbital was approximately half that of 4-OH-mephenytoin over the same time after mephenytoin administration. One EM received similar doses of R- and S-mephobarbital on separate occasions. Urinary recovery of 4-OH-mephobarbital was 33% and < 1%, respectively. These results suggest that mephobarbital is stereoselectively hydroxylated by the same drug metabolizing enzyme that is responsible for the stereoselective aromatic hydroxylation of mephenytoin.