PHARMACOGENETIC CHARACTERISTICS OF THE EOSINOPHILIA-MYALGIA-SYNDROME

被引：26

作者：

FLOCKHART, DA ^{[1
]}

CLAUW, DJ ^{[1
]}

SALE, EB ^{[1
]}

HEWETT, J ^{[1
]}

WOOSLEY, RL ^{[1
]}

机构：

[1] GEORGETOWN UNIV, MED CTR, DEPT MED, DIV RHEUMATOL, WASHINGTON, DC 20007 USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 1994年 / 56卷 / 04期

关键词：

D O I：

10.1038/clpt.1994.154

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

This study tested the hypothesis that patterns of xenobiotic metabolism in patients with eosinophilia-myalgia syndrome (EMS) differed from healthy control subjects. We determined the genotypes of 27 EMS patients with EMS and 114 control subjects for the cytochrome P450 CYP2D6 polymorphism. The metabolic phenotypes of patients with EMS for S-mephenytoin hydroxylation (n = 17) and dapsone acetylation (n = 19) were determined and compared with 29 healthy control subjects. The incidence of the CYP2D6 poor metabolizer genotype (mutant/mutant) was 0.185 in patients with EMS and 0.061 in control subjects (Mantel-Haenszel, chi(2) = 7.213, p = 0.007). The mephenytoin S/R ratios were 0.39 +/- 0.23 in patients with EMS versus 0.18 +/- 0.13 in control subjects (p less than or equal to 0.005). There was no difference in dapsone acetylation between the two groups. A pattern of xenobiotic metabolism may play a role in the pathogenesis of EMS, but the precise role that it plays remains unclear.

引用

页码：398 / 405

页数：8

共 40 条

[1] CLINICAL CONSEQUENCES OF POLYMORPHIC DRUG OXIDATION [J].

ALVAN, G .

FUNDAMENTAL & CLINICAL PHARMACOLOGY, 1991, 5 (03) :209-228

[2] ALTERED DISTRIBUTION OF DEBRISOQUINE OXIDATION PHENOTYPES IN PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS [J].

BAER, AN ;

MCALLISTER, CB ;

WILKINSON, GR ;

WOOSLEY, RL ;

PINCUS, T .

ARTHRITIS AND RHEUMATISM, 1986, 29 (07) :843-850

[3] AN INVESTIGATION OF THE CAUSE OF THE EOSINOPHILIA-MYALGIA SYNDROME ASSOCIATED WITH TRYPTOPHAN USE [J].

BELONGIA, EA ;

HEDBERG, CW ;

GLEICH, GJ ;

WHITE, KE ;

MAYENO, AN ;

LOEGERING, DA ;

DUNNETTE, SL ;

PIRIE, PL ;

MACDONALD, KL ;

OSTERHOLM, MT .

NEW ENGLAND JOURNAL OF MEDICINE, 1990, 323 (06) :357-365

[4] QUANTIFICATION AND MECHANISM OF THE FLUOXETINE AND TRICYCLIC ANTIDEPRESSANT INTERACTION [J].

BERGSTROM, RF ;

PEYTON, AL ;

LEMBERGER, L .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 1992, 51 (03) :239-248

[5] IMPORTANCE OF GENETIC-FACTORS IN THE REGULATION OF DIAZEPAM METABOLISM - RELATIONSHIP TO S-MEPHENYTOIN, BUT NOT DEBRISOQUIN, HYDROXYLATION PHENOTYPE [J].

BERTILSSON, L ;

HENTHORN, TK ;

SANZ, E ;

TYBRING, G ;

SAWE, J ;

VILLEN, T .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 1989, 45 (04) :348-355

[6] ACTIVITY OF OXIDATIVE ROUTES OF METABOLISM OF DEBRISOQUIN, MEPHENYTOIN, AND DAPSONE IS UNRELATED TO THE PATHOGENESIS OF VINYL-CHLORIDE INDUCED DISEASE [J].

BLACK, C ;

CSUKA, ME ;

LUPOLI, S ;

WILKINSON, GR ;

BRANCH, RA .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 1992, 52 (06) :659-667

[7] DEBRISOQUINE SPARTEINE HYDROXYLATION GENOTYPE AND PHENOTYPE - ANALYSIS OF COMMON MUTATIONS AND ALLELES OF CYP2D6 IN A EUROPEAN POPULATION [J].

BROLY, F ;

GAEDIGK, A ;

HEIM, M ;

EICHELBAUM, M ;

MORIKE, K ;

MEYER, UA .

DNA AND CELL BIOLOGY, 1991, 10 (08) :545-558

[8] ROLE OF P450IID6, THE TARGET OF THE SPARTEINE-DEBRISOQUIN OXIDATION POLYMORPHISM, IN THE METABOLISM OF IMIPRAMINE [J].

BROSEN, K ;

ZEUGIN, T ;

MEYER, UA .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 1991, 49 (06) :609-617

[9] FLUOXETINE AND NORFLUOXETINE ARE POTENT INHIBITORS OF P450IID6 - THE SOURCE OF THE SPARTEINE DEBRISOQUINE OXIDATION POLYMORPHISM [J].

BROSEN, K ;

SKJELBO, E .

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1991, 32 (01) :136-137

[10] RELATIONSHIP OF CYP2D6 (DEBRISOQUINE HYDROXYLASE) GENOTYPE TO BREAST-CANCER SUSCEPTIBILITY [J].

BUCHERT, ET ;

WOOSLEY, RL ;

SWAIN, SM ;

OLIVER, SJ ;

COUGHLIN, SS ;

PICKLE, L ;

TROCK, B ;

RIEGEL, AT .

PHARMACOGENETICS, 1993, 3 (06) :322-327

← 1 2 3 4 →