Stereoselectivity in the urinary excretion of the mercapturates of (R-) and (S-) alpha-bromoisovalerylurea in man.
1. alpha-Bromoisovalerylurea (BIU) is a racemic drug that is metabolized by glutathione conjugation. The urinary excretion of the separate diastereomeric mercapturates formed from (S)- and (R)-BIU in healthy young human volunteers was investigated. 2. A pronounced stereoselectivity was observed: the mercapturate formed from R-BIU was excreted with a t1/2 of 1.5 +/- 0.4 h, while that from S-BIU showed a t1/2 of 3.1 +/- 1.3 h. Moreover, 22.5 +/- 4.3 and 5.7 +/- 1.6% of the dose, respectively, was excreted as each mercapturate diastereomer in 24 h. 3. This is the first example of stereoselectivity in the elimination of a substrate for glutathione conjugation in man.
te Koppele
J M
JM
Division of Toxicology, University of Leiden, The Netherlands.
Schipper
C
C
Breimer
D D
DD
Mulder
G J
GJ
D000111:Acetylcysteine / Q000032:analysis* / Q000493:pharmacokinetics; D000328:Adult; D001968:Bromisovalum / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D005978:Glutathione / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D008297:Male; D012463:Saliva / Q000378:metabolism; D013237:Stereoisomerism; D014508:Urea / Q000031:analogs & derivatives*
D001968:Bromisovalum; D014508:Urea; D005978:Glutathione; D000111:Acetylcysteine