%0 Journal Article %A C Tang %A K Zhang %A F Lepage %A R H Levy %A T A Baillie %T Metabolic chiral inversion of stiripentol in the rat. II. Influence of route of administration. %D 1994 %J Drug Metabolism and Disposition %P 554-560 %V 22 %N 4 %X As described in the accompanying study, it was found that when the S enantiomer of stiripentol [(S)-STP] was given orally to rats, blood specimens contained only (S)-STP, whereas following administration of an equivalent dose of (R)-STP, both R and S forms of the drug were detected in the systemic circulation. In the present study, we investigated the influence of route of administration on this apparently unidirectional chiral inversion of (R)-STP in the rat. When (R)-STP was given either intravenously (60 mg kg-1) or intraperitoneally (300 mg kg-1), the inversion phenomenon was not observed, indicating that the process must take place presystemically. Following oral administration of either enantiomer of STP, it was found that the drug present at various points along the gastrointestinal tract became progressively enriched in molecules of R configuration, such that the free STP in cecum, large intestine, and feces consisted largely of the R enantiomer, regardless of the configuration of the administered drug. In a parallel in vitro study, it was demonstrated that STP undergoes acid-catalyzed racemization, the rate of which is appreciable at the pH value of the rat stomach (pH approximately 4). On the basis of these observations, it is proposed that the apparent metabolic chiral inversion of (R)-STP results from the combination of at least two factors: 1) partial acid-catalyzed racemization in gastric acid (that affects both enantiomers equally), and 2) enantioselectivity in one or more of the processes involved in the absorption, first pass metabolism or biliary excretion of STP, such that the S isomer appears selectively in the systemic circulation, whereas the R enantiomer is eliminated preferentially in the feces. %U https://dmd.aspetjournals.org/content/dmd/22/4/554.full.pdf