Direct high pressure liquid chromatographic analysis and preliminary pharmacokinetics of enantiomers of oxazepam and temazepam with their corresponding glucuronide conjugates.
Three high pressure liquid chromatographic systems for the separation of oxazepam, temazepam and their glucuronides (system A), the separation of their R,S glucuronide diastereomers (system B) and the chiral separation of the parent drugs (system C) are described. Preliminary pharmacokinetics of R,S-oxazepam and R,S-temazepam in a human volunteer reveal that the protein binding of the glucuronides is lower than that of the parent drugs, but that there is no difference in protein binding between the R-oxazepam/temazepam and S-oxazepam/temazepam and their corresponding glucuronides. The S-glucuronide is the main metabolite formed and excreted by man. The plasma ratio R/S-glucuronide is 1:1 for both oxazepam and temazepam. The renal clearance of R-temazepam, and S-temazepam are similar, and those of R-oxazepam and S-oxazepam tend to be different.
Vree
T B
TB
Department of Clinical Pharmacy, University Hospital Nijmegen, The Netherlands.
Baars
A M
AM
Wuis
E W
EW
D002851:Chromatography, High Pressure Liquid; D005965:Glucuronates / Q000097:blood / Q000378:metabolism / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D010076:Oxazepam / Q000493:pharmacokinetics*; D011485:Protein Binding; D013237:Stereoisomerism; D013693:Temazepam / Q000493:pharmacokinetics*
D005965:Glucuronates; D010076:Oxazepam; D013693:Temazepam