Biotransformations and plasma-level curves of chiral 1,4-benzodiazepine-2-ones.
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.
D000818:Animals; D001569:Benzodiazepines / Q000097:blood* / Q000378:metabolism; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D002855:Chromatography, Thin Layer; D002942:Circular Dichroism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D001569:Benzodiazepines