Mephenytoin stereoselective elimination in the rat: II. Comparison of mephenytoin stereoselective clearance during chronic intravenous and hepatic portal vein administration.
The stereoselective clearances of R- and S-mephenytoin were determined in rats receiving either an intravenous or hepatic portal vein infusion of racemic mephenytoin. The mean +/- SD intravenous clearances of R- and S-mephenytoin were 1630 +/- 250 ml/hr and 630 +/- 250 ml/hr, respectively. The corresponding portal vein clearances for these enantiomers were 2560 +/- 1230 ml/hr (R-mephenytoin) and 540 +/- 230 ml/hr (S-mephenytoin). In spite of the slightly higher clearance for R-mephenytoin following portal vein administration, the difference between the intravenous and portal vein clearances for R- or S-mephenytoin were not found to be significant. Subsequent computer simulations of the data indicated there was less than a 5% probability that this result could be attributed solely to interanimal variability in drug clearance. The estimated extraction ratio of R-mephenytoin by the liver was modest and suggested mephenytoin may undergo a substantial degree of extrahepatic elimination in the rat.
Akrawi
S H
SH
College of Pharmacy, University of Baghdad, Iraq.
Wedlund
P J
PJ
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002849:Chromatography, Gas; D006827:Hydantoins / Q000378:metabolism* / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D008297:Male; D008617:Mephenytoin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism* / Q000493:pharmacokinetics*; D011169:Portal Vein; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D001798:Blood Proteins; D006827:Hydantoins; C014544:ethylphenylhydantoin; D008617:Mephenytoin