ENANTIOSELECTIVE PHARMACOKINETICS OF HOMOCHLORCYCLIZINE .2. DISPOSITION AND METABOLISM OF (+)-, (-)- AND RACEMIC HOMOCHLORCYCLIZINE AFTER ORAL-ADMINISTRATION TO MAN

被引:6
作者
NISHIKATA, M
NOMURA, A
ISEKI, K
MIYAZAKI, K
NAKAI, A
FUSHIDA, H
MIYAKE, K
ARITA, T
机构
[1] HOKKAIDO UNIV,SCH MED,DEPT CARDIOVASC MED,SAPPORO,HOKKAIDO 060,JAPAN
[2] MUKOGAWA WOMENS UNIV,FAC PHARMACEUT SCI,NISHINOMIYA,HYOGO 663,JAPAN
关键词
HOMOCHLORCYCLIZINE; ENANTIOSELECTIVE; METABOLISM; PHARMACOKINETICS; PROTEIN BINDING; SIDE EFFECTS;
D O I
10.1007/BF02285097
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:533 / 538
页数:6
相关论文
共 13 条
[1]   LAMOTRIGINE, A NEW ANTICONVULSANT - PHARMACOKINETICS IN NORMAL HUMANS [J].
COHEN, AF ;
LAND, GS ;
BREIMER, DD ;
YUEN, WC ;
WINTON, C ;
PECK, AW .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1987, 42 (05) :535-541
[2]  
HUCKER HB, 1978, DRUG METAB DISPOS, V6, P659
[3]   ENANTIOSELECTIVE ASPECTS OF DRUG-ACTION AND DISPOSITION - THERAPEUTIC PITFALLS [J].
JAMALI, F ;
MEHVAR, R ;
PASUTTO, FM .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1989, 78 (09) :695-715
[4]  
KUNTZMAN R, 1965, J PHARMACOL EXP THER, V149, P29
[5]   CHIRALITY - CLINICAL PHARMACOKINETIC AND PHARMACODYNAMIC CONSIDERATIONS [J].
LEE, EJD ;
WILLIAMS, KM .
CLINICAL PHARMACOKINETICS, 1990, 18 (05) :339-345
[6]  
NISHIKATA M, 1992, CHEM PHARM BULL, V40, P1341
[7]   CLINICAL PHARMACOKINETICS OF H-1-RECEPTOR ANTAGONISTS (THE ANTIHISTAMINES) [J].
PATON, DM ;
WEBSTER, DR .
CLINICAL PHARMACOKINETICS, 1985, 10 (06) :477-497
[8]  
PORTER CC, 1975, DRUG METAB DISPOS, V3, P189
[9]  
TSUTSUMI J, 1970, YAKUZAIGAKU, V30, P258
[10]   IMPORTANCE OF DRUG ENANTIOMERS IN CLINICAL-PHARMACOLOGY [J].
WILLIAMS, K ;
LEE, E .
DRUGS, 1985, 30 (04) :333-354