Pharmacokinetics and metabolism of halazepam in naive and dependent dogs.
The pharmacokinetic profiles of halazepam (HL) and its metabolites, desmethyldiazepam (DMDZ), oxazepam (OX), 3-hydroxyhalazepam (OH-HL), and conjugates of oxazepam (OX-CONJ) and 3-hydroxyhalazepam (OH-HL-CONJ) were studied in 4 naive dogs following single intravenous (2 mg/kg) and oral (112.5 mg/kg) administrations of HL and in 5 dependent dogs chronically dosed with HL (450 mg/kg/day q.i.d.). HL is rapidly metabolized to DMDZ as the principal metabolite but appreciable levels of HL, OX and OH-HL were measured in plasma and the brain tissue. High levels of conjugated metabolites were measured in plasma. The steady-state plasma concentrations of HL and its unconjugated metabolites can be predicted from the single dose study. Halazepam does not serve as a simple prodrug for DMDZ in producing physical dependence in dogs.
Department of Anesthesiology, University of Kentucky, Lexington 40536.
E P
EP
Wala
J W
JW
Sloan
W R
WR
Martin
T
T
Pruitt
D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism* / Q000493:pharmacokinetics; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000378:metabolism* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005260:Female; D015394:Molecular Structure; D012015:Reference Standards; D012016:Reference Values; D019966:Substance-Related Disorders / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D001569:Benzodiazepines; C010175:halazepam