Codeine intoxication associated with ultrarapid CYP2D6 metabolism

被引：458

作者：

Gasche, Y

Daali, Y

Fathi, M

Chiappe, A

Cottini, S

Dayer, P

Desmeules, J

机构：

[1] Univ Hosp Geneva, Div Med Intens Care, CH-1211 Geneva, Switzerland

[2] Univ Hosp Geneva, Div Clin Pharmacol & Toxicol, CH-1211 Geneva, Switzerland

[3] Univ Hosp Geneva, Div Clin Chem, CH-1211 Geneva, Switzerland

[4] Univ Hosp Geneva, Dept Anesthesiol Pharmacol & Surg Intens Care, Div Surg Intens Care, CH-1211 Geneva, Switzerland

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2004年 / 351卷 / 27期

关键词：

D O I：

10.1056/NEJMoa041888

中图分类号：

R5 [内科学];

学科分类号：

1002 [临床医学]; 100201 [内科学];

摘要：

Life-threatening opioid intoxication developed in a patient after he was given small doses of codeine for the treatment of a cough associated with bilateral pneumonia. Codeine is bioactivated by CYP2D6 into morphine, which then undergoes further glucuronidation. CYP2D6 genotyping showed that the patient had three or more functional alleles, a finding consistent with ultrarapid metabolism of codeine. We attribute the toxicity to this genotype, in combination with inhibition of CYP3A4 activity by other medications and a transient reduction in renal function.

引用

收藏

页码：2827 / 2831

页数：5

相关论文

共 16 条

[1]

Molecular genetics of CYP2D6:: Clinical relevance with focus on psychotropic drugs [J].

Bertilsson, L ;

Dahl, ML ;

Dalén, P ;

Al-Shurbaji, A .

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2002, 53 (02) :111-122

[2]

Caraco Y, 1999, J PHARMACOL EXP THER, V290, P413

[3]

DAHL ML, 1995, J PHARMACOL EXP THER, V274, P516

[4]

BIOACTIVATION OF THE NARCOTIC DRUG CODEINE IN HUMAN-LIVER IS MEDIATED BY THE POLYMORPHIC MONOOXYGENASE CATALYZING DEBRISOQUINE 4-HYDROXYLATION (CYTOCHROME-P-450 DBL/BUFI) [J].

DAYER, P ;

DESMEULES, J ;

LEEMANN, T ;

STRIBERNI, R .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1988, 152 (01) :411-416

[5]

IMPACT OF ENVIRONMENTAL AND GENETIC-FACTORS ON CODEINE ANALGESIA [J].

DESMEULES, J ;

GASCON, MP ;

DAYER, P ;

MAGISTRIS, M .

EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1991, 41 (01) :23-26

[6]

The effect of grapefruit juice and seville orange juice on the pharmacokinetics of dextromethorphan: The role of gut CYP3A and P-glycoprotein [J].

Di Marco, MP ;

Edwards, DJ ;

Wainer, IW ;

Ducharme, MP .

LIFE SCIENCES, 2002, 71 (10) :1149-1160

[7]

INHERITED AMPLIFICATION OF AN ACTIVE GENE IN THE CYTOCHROME-P450 CYP2D LOCUS AS A CAUSE OF ULTRARAPID METABOLISM OF DEBRISOQUINE [J].

JOHANSSON, I ;

LUNDQVIST, E ;

BERTILSSON, L ;

DAHL, ML ;

SJOQVIST, F ;

INGELMANSUNDBERG, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (24) :11825-11829

[8]

Incidence of adverse drug reactions in hospitalized patients - A meta-analysis of prospective studies [J].

Lazarou, J ;

Pomeranz, BH ;

Corey, PN .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1998, 279 (15) :1200-1205

[9]

Pharmacogenetics and adverse drug reactions [J].

Meyer, UA .

LANCET, 2000, 356 (9242) :1667-1671

[10]

Optimized strategy for rapid cytochrome P450 2D6 genotyping by real-time long PCR [J].

Müller, B ;

Zöpf, K ;

Bachofer, J ;

Steimer, W .

CLINICAL CHEMISTRY, 2003, 49 (10) :1624-1631