Mephenytoin stereoselective elimination in the rat: I. Enantiomeric disposition following intravenous administration.

The stereoselective disposition of mephenytoin was characterized after an intravenous bolus dose of racemic mephenytoin to rats being infused with 50% polyethylene glycol 400/50% saline via the jugular and hepatic portal vein. No significant influence on mephenytoin disposition was noted due to the site selected for the administration of the 50% polyethylene glycol 400 solution. The mean (+/- SD) clearance of R- and S-mephenytoin were 171 +/- 58 ml/hr (R) and 110 +/- 37 ml/hr (S), and the mean (+/- SD) volumes of distribution were 325 +/- 75 ml (R) and 359 +/- 72 ml (S). The clearance of R-mephenytoin was significantly larger than the clearance of S-mephenytoin, but this stereoselective difference is of opposite stereochemistry and of much smaller magnitude than the stereoselective difference reported for these enantiomers in man. The difference in the volumes of distribution of R- and S-mephenytoin was not significant.