Mephenytoin stereoselective elimination in the rat: II. Comparison of mephenytoin stereoselective clearance during chronic intravenous and hepatic portal vein administration

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Abstract
Summary 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.

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