Rates of in vivo methylation of desipramine and nortriptyline

被引:7
作者
Kurpius, MP
Alexander, B
机构
[1] Univ Iowa, Coll Pharm, Iowa City, IA USA
[2] Univ Iowa, Coll Med, Iowa City, IA USA
[3] Iowa City Dept Vet Affairs Med Ctr, Dept Pharmacol & Psychiat, Iowa City, IA USA
来源
PHARMACOTHERAPY | 2006年 / 26卷 / 04期
关键词
methylation; tricyclic antidepressants; desipramine; nortriptyline; clinical monitoring;
D O I
10.1592/phco.26.4.505
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Routine monitoring of an 81-year-old man receiving treatment with nortriptyline for generalized anxiety disorder and depression revealed plasma concentrations of both amitriptyline and nortriptyline. In humans, the tricyclic antidepressant (TCA) tertiary amines imipramine and amitriptyline are typically metabolized by demethylation to the secondary active metabolites desipramine and nortriptyline, respectively. However, to our knowledge, methylation of secondary amine TCAs has been reported in only one case report of nortriptyline overdose and in two studies involving desipramine. In a retrospective analysis of patients from five Veterans Affairs medical centers, the rate of methylation of desipramine and nortriptyline was 8.9 % (five of 56 patients) and 14.6% (36 of 247), respectively. Possible explanations for methylation include genetic polymorphisms in cytochrome P450 metabolizing enzymes, polymorphism of amine N-methyltransferase enzyme, drug-drug interactions, smoking, and alcohol consumption. However, the mechanism by which methylation occurs is unclear and warrants further investigation. Awareness of the phenomenon could help in discouraging repeated laboratory tests and unnecessary adjustments of drug therapies, resulting in cost savings and better patient outcomes.
引用
收藏
页码:505 / 510
页数:6
相关论文
共 31 条
[1]  
Ansher S. S., 1990, CONJUGATION REACTION, P233
[2]  
ANSHER SS, 1986, J BIOL CHEM, V261, P3996
[3]  
Baumann P, 2002, PHARMACOGENETICS OF PSYCHOTROPIC DRUGS, P181, DOI 10.1017/CBO9780511543944.009
[4]   Polymorphic cytochromes P450 and drugs used in psychiatry [J].
Coutts, RT ;
Urichuk, LJ .
CELLULAR AND MOLECULAR NEUROBIOLOGY, 1999, 19 (03) :325-354
[5]  
FRIEDEL RO, 1982, J CLIN PSYCHIAT, V43, P37
[6]   PHARMACOGENETICS .1. [J].
GIBALDI, M .
ANNALS OF PHARMACOTHERAPY, 1992, 26 (01) :121-126
[7]   Dextromethorphan O-demethylation polymorphism in an African-American population [J].
He, N ;
Daniel, HI ;
Hajiloo, L ;
Shockley, D .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1999, 55 (06) :457-459
[8]   Polymorphic human cytochrome P450 enzymes: an opportunity for individualized drug treatment [J].
Ingelman-Sundberg, M ;
Oscarson, M ;
McLellan, RA .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1999, 20 (08) :342-349
[9]   Drug metabolism and ageing [J].
Kinirons, MT ;
O'Mahony, MS .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2004, 57 (05) :540-544
[10]  
Lemke T., 2002, FOYES PRINCIPLES MED, V5th, P174