Mephenytoin stereoselective elimination in the rat: III. Stereoselective time course of induction during chronic hepatic portal vein administration.
The blood concentrations of R- and S-mephenytoin were followed in seven rats over a 5-8 day period during a hepatic portal vein infusion of racemic mephenytoin. In all but two rats, both of the enantiomers achieved an initial steady-state level before a measurable change was observed in their blood concentrations. In each case, the decrease in the initial S-mephenytoin steady state blood level occurred after the change in R-mephenytoin was apparent. During the period of study, the mean +/- SD portal vein clearance of S-mephenytoin increased from 96 +/- 33 ml/h to 450 +/- 160 ml/h. The mean +/- SD portal vein clearance of R-mephenytoin increased from 170 +/- 50 ml/h to 2400 +/- 1600 ml/h. The larger increase in the portal vein clearance for the R-enantiomer resulted in the R/S-mephenytoin clearance ratio over this same time period changing from 1.8 +/- 0.2 to 5.2 +/- 1.8. Attempts to describe the time course of change in the clearance of S- or R-mephenytoin using a previously reported model of induction were unsuccessful. The induction time course did suggest, however, that the rate of induction may be similar for each enantiomer.
Akrawi
S H
SH
College of Pharmacy, University of Baghdad, Iraq.
Wedlund
P J
PJ
D000818:Animals; D006706:Homeostasis; D007262:Infusions, Intravenous; D007700:Kinetics; D008297:Male; D008617:Mephenytoin / Q000008:administration & dosage / Q000097:blood*; D008657:Metabolic Clearance Rate; D011169:Portal Vein; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013997:Time Factors
D008617:Mephenytoin