Enantioselective pharmacokinetics of homochlorcyclizine. II: Disposition and metabolism of (+)-, (-)- and racemic homochlorcyclizine after oral administration to man.
The pharmacokinetics of a single oral dose of 20 mg (+)-, (-)- and racemic homochlorcyclizine (HCZ) have been studied in humans. The formation of the quarternary ammonium-linked glucuronide was an important metabolic pathway, and the metabolic process was enantioselective as a result of differing urinary excretion rates of (+)-, (-)- and racemic glucuronide. There were significant differences between (+)-, (-)- and racemic HCZ in AUC (0-14 h) and plasma protein binding, but all HCZ enantiomers were slowly absorbed and eliminated (elimination half-lives about 11 h). The results shows help to establish a more efficient dosage regimen for HCZ therapy.
Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
M
M
Nishikata
A
A
Nomura
K
K
Iseki
K
K
Miyazaki
A
A
Nakai
H
H
Fushida
K
K
Miyake
T
T
Arita
D000284:Administration, Oral; D000328:Adult; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003501:Cyclizine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D004912:Erythrocytes / Q000378:metabolism; D005965:Glucuronates / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D011485:Protein Binding; D012016:Reference Values; D013237:Stereoisomerism
D001798:Blood Proteins; D005965:Glucuronates; D006634:Histamine H1 Antagonists; C034022:homochlorocyclizine; D003501:Cyclizine