THE GENETIC-POLYMORPHISM OF DEBRISOQUINE SPARTEINE METABOLISM - CLINICAL ASPECTS

被引:361
作者
EICHELBAUM, M
GROSS, AS
机构
[1] Dr Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, D-7000 Stuttgart 50
关键词
D O I
10.1016/0163-7258(90)90025-W
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
It has been established that the metabolism of more than twenty drugs, including antiarrhythmics, β-adrenoceptor antagonists, antidepressants, opiates and neuroleptics is catalyzed by cytochrome P-450dbl. The activity of this P-450 isozyme is under genetic rather than environmental control. This article discusses the therapeutic implications for each of the classes of drugs affected by this genetic polymorphism in drug metabolism. Not only are the problems associated with poor metabolizers who are unable to metabolize the compounds discussed, but it is also emphasized that it is difficult to attain therapeutic plasma concentrations for some drugs in high activity extensive metabolizers. © 1990.
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页码:377 / 394
页数:18
相关论文
共 125 条
  • [91] METABOLISM OF METHOXYPHENAMINE IN EXTENSIVE AND POOR METABOLIZERS OF DEBRISOQUIN
    ROY, SD
    HAWES, EM
    MCKAY, G
    KORCHINSKI, ED
    MIDHA, KK
    [J]. CLINICAL PHARMACOLOGY & THERAPEUTICS, 1985, 38 (02) : 128 - 133
  • [92] PHARMACODYNAMICS AND SIDE-EFFECTS OF FLECAINIDE ACETATE
    SALERNO, DM
    GRANRUD, G
    SHARKEY, P
    KREJCI, J
    LARSON, T
    ERLIEN, D
    BERRY, D
    HODGES, M
    [J]. CLINICAL PHARMACOLOGY & THERAPEUTICS, 1986, 40 (01) : 101 - 107
  • [93] POLYMORPHIC DEXTROMETHORPHAN METABOLISM - CO-SEGREGATION OF OXIDATIVE O-DEMETHYLATION WITH DEBRISOQUIN HYDROXYLATION
    SCHMID, B
    BIRCHER, J
    PREISIG, R
    KUPFER, A
    [J]. CLINICAL PHARMACOLOGY & THERAPEUTICS, 1985, 38 (06) : 618 - 624
  • [94] SCHWARTZKOPFF B, 1983, ARZNEIMITTEL-FORSCH, V33-1, P153
  • [95] IMPAIRED OXIDATION OF DEBRISOQUINE IN PATIENTS WITH PERHEXILINE NEUROPATHY
    SHAH, RR
    OATES, NS
    IDLE, JR
    SMITH, RL
    LOCKHART, JDF
    [J]. BRITISH MEDICAL JOURNAL, 1982, 284 (6312) : 295 - 299
  • [96] PREDICTION OF SUBCLINICAL PERHEXILINE NEUROPATHY IN A PATIENT WITH INBORN ERROR OF DEBRISOQUINE HYDROXYLATION
    SHAH, RR
    OATES, NS
    IDLE, JR
    SMITH, RL
    LOCKHART, JDF
    [J]. AMERICAN HEART JOURNAL, 1983, 105 (01) : 159 - 161
  • [97] POLYMORPHISM OF PROPAFENONE METABOLISM AND DISPOSITION IN MAN - CLINICAL AND PHARMACOKINETIC CONSEQUENCES
    SIDDOWAY, LA
    THOMPSON, KA
    BRENDANMCALLISTER, C
    WANG, T
    WILKINSON, GR
    RODEN, DM
    WOOSLEY, RL
    [J]. CIRCULATION, 1987, 75 (04) : 785 - 791
  • [98] WHY HYPERTENSIVE PATIENTS VARY IN THEIR RESPONSE TO ORAL DEBRISOQUINE
    SILAS, JH
    LENNARD, MS
    TUCKER, GT
    SMITH, AJ
    MALCOLM, SL
    MARTEN, TR
    [J]. BRITISH MEDICAL JOURNAL, 1977, 1 (6058) : 422 - 425
  • [99] SJOQVIST F, 1986, ETHNIC DIFFERENCES R, P169
  • [100] 2 MUTANT ALLELES OF THE HUMAN CYTOCHROME-P-450DB1 GENE (P450C2D1) ASSOCIATED WITH GENETICALLY DEFICIENT METABOLISM OF DEBRISOQUINE AND OTHER DRUGS
    SKODA, RC
    GONZALEZ, FJ
    DEMIERRE, A
    MEYER, UA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (14) : 5240 - 5243