HYDROXYLATION POLYMORPHISMS OF DEBRISOQUINE AND MEPHENYTOIN IN EUROPEAN POPULATIONS

被引:415
作者
ALVAN, G
BECHTEL, P
ISELIUS, L
GUNDERTREMY, U
机构
[1] SOUTHAMPTON GEN HOSP,GENET EPIDEMIOL RES GRP,SOUTHAMPTON SO9 4XY,HANTS,ENGLAND
[2] CHU BESANCON,HOP JEAN MINJOZ,DEPT CLIN PHARMACOL,F-25030 BESANCON,FRANCE
[3] BUNDESGESUNDHEITSAMT,INST ARZNEIMITTEL,W-1000 BERLIN 33,GERMANY
关键词
debrisoquine; dextromethorphan; Genetic polymorphism; mephenytoin; meta-analysis; oxidative drug metabolism; pharmacogenetics; sparteine;
D O I
10.1007/BF00316090
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
European data on the polymorphic metabolism of debrisoquine, sparteine, dextromethorphan and mephenytoin have been collected. No significant difference in phenotype frequencies was found between the separate series for debrisoquine, sparteine and dextromethorphan, which supports the claim that these probe drugs reflect the same enzyme polymorphism. The mean frequency of the phenotype slow debrisoquine metaboliser was 7.65% based on 5005 determinations. The overall mean reflecting all three drugs and 8764 determinations was 7.40%. This is consistent with a gene frequency of 0.27 (95% confidence interval 0.26-0.28). The overall mean of the phenotype slow metaboliser of mephenytoin was 3.52% corresponding to a gene frequency of 0.19 (confidence interval 0.17-0.20). The incidence of slow metabolism of debrisoquine and possibly also of S-mephenytoin was homogeneous in the samples from European populations. This is of considerable interest as interethnic differences are now being found both in the phenotypic characters as well as the genotypes of polymorphic drug oxidation. © 1990 Springer-Verlag.
引用
收藏
页码:533 / 537
页数:5
相关论文
共 39 条
[1]   POLYMORPHISM OF DEBRISOQUINE HYDROXYLATION AMONG FINNS AND LAPPS [J].
ARVELA, P ;
KIRJARINTA, M ;
KIRJARINTA, M ;
KARKI, N ;
PELKONEN, O .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1988, 26 (05) :601-603
[2]  
BECHTEL P, 1986, ANN BIOL CLIN-PARIS, V44, P361
[3]   DEBRISOQUIN OXIDATION POLYMORPHISM IN A SPANISH POPULATION [J].
BENITEZ, J ;
LLERENA, A ;
COBALEDA, J .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1988, 44 (01) :74-77
[4]  
BERTILSSON L, 1989, TOPICS PHARM SCI
[5]  
BREIMER DD, 1988, MICROSOMES DRUG OXID, P232
[6]  
BROSEN K, 1985, ACTA PHARMACOL TOX, V57, P357
[7]   CLINICAL-SIGNIFICANCE OF THE SPARTEINE-DEBRISOQUINE OXIDATION POLYMORPHISM [J].
BROSEN, K ;
GRAM, LF .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1989, 36 (06) :537-547
[8]   MEPHENYTOIN AND SPARTEINE OXIDATION - GENETIC POLYMORPHISMS IN DENMARK [J].
DROHSE, A ;
BATHUM, L ;
BROSEN, K ;
GRAM, LF .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1989, 27 (05) :620-625
[9]   THE INFLUENCE OF ENZYME-INDUCTION ON POLYMORPHIC SPARTEINE OXIDATION [J].
EICHELBAUM, M ;
MINESHITA, S ;
OHNHAUS, EE ;
ZEKORN, C .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1986, 22 (01) :49-53
[10]   DEFECTIVE N-OXIDATION OF SPARTEINE IN MAN - NEW PHARMACOGENETIC DEFECT [J].
EICHELBAUM, M ;
SPANNBRUCKER, N ;
STEINCKE, B ;
DENGLER, HJ .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1979, 16 (03) :183-187