Biotransformations and plasma-level curves of chiral 1,4-benzodiazepine-2-ones

Abstract

Biotransformations of chiral 1,4-benzodiazepine-2-ones, (S)- and (R)-1 (7-chloro-1,3-dihydro-3 (S and R)-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one) in untreated and phenobarbital-pretreated rats were investigated. In urine, a 4'-oxygenated metabolite (compound 2) was identified as the biotransformation product from both enantiomers, (S)-2 being present in much higher amounts than (R)-2. Unchanged parent compounds were not found in urine. In plasma, 3'- and 4'-oxygenated metabolites were identified after administration of (S)-1 and (R)-1, respectively. The metabolite possessing an R-configuration was present in much lower amounts. The maximum concentrations of (R)-1 in plasma, following a single dose, was about 6 time as high as the maximum plasma concentration of (S)-1. Faster biotransformation and elimination of (S)-1 is assumed to be the explanation of these findings.

Unequal Disposition of Enantiomers of the Organic Cation Oxyphenonium in the Rat Isolated Perfused Liver

“…Enantioselective hydroxylations have been described for many compounds (Honma et a1 1985;Vukusic et al 1985;Ochs et al 1986). The product [2], after oxidative metabolism of oxyphenonium may have an &value close to that of oxyphenonium, but it can be hydrolysed.…”