The importance of cytochrome P450 monooxygenase CYP2D6 in palliative medicine

被引:45
作者
Davis, MP [1 ]
Homsi, J [1 ]
机构
[1] Cleveland Clin Fdn, Harry R Horvitz Ctr Palliat Med, Cleveland, OH 44195 USA
关键词
CYP2D6; palliative medicine; drug metabolism; drug interactions; ethnic differences; pharmacokinetics;
D O I
10.1007/s005200000222
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The enzymes in the cytochrome p450 monooxygenase system (CYP) are the major enzymes responsible for metabolizing medications. The CYP2D6 isomer is responsible for metabolizing certain opioids, neuroleptics, antidepressants and cardiac medications. Owing to CYP2D6's low capacity and high affinity it is easily saturated by substrate and/or inhibited, resulting in pharmacokinetic interactions. Polymorphisms of the structural gene are common, leading to wide inter-individual and ethnic differences in drug metabolism. Clinically important drug interactions, which may be anticipated in the palliative medicine population, are reviewed.
引用
收藏
页码:442 / 451
页数:10
相关论文
共 105 条
[81]   Influence of hydroxychloroquine on the bioavailability of oral metoprolol [J].
Somer, M ;
Kallio, J ;
Pesonen, U ;
Pyykkö, K ;
Huupponen, R ;
Scheinin, M .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2000, 49 (06) :549-554
[82]   The effect of cytochrome P450 2D6 genotypes on haloperidol metabolism: A preliminary study in a psychiatric population [J].
Someya, T ;
Suzuki, Y ;
Shimoda, K ;
Hirokane, G ;
Morita, S ;
Yokono, A ;
Inoue, Y ;
Takahashi, S .
PSYCHIATRY AND CLINICAL NEUROSCIENCES, 1999, 53 (05) :593-597
[83]   CYP2D6 inhibition in patients treated with sertraline [J].
Sproule, BA ;
Otton, SV ;
Cheung, SW ;
Zhong, XH ;
Romach, MK ;
Sellers, EM .
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY, 1997, 17 (02) :102-106
[84]  
Steijns LSW, 1998, CLIN CHEM, V44, P914
[85]   Phenotyping of drug-metabolizing enzymes in adults: a review of in-vivo cytochrome P450 phenotyping probes [J].
Streetman, DS ;
Bertino, JS ;
Nafziger, AN .
PHARMACOGENETICS, 2000, 10 (03) :187-216
[86]   Gender-related differences in pharmacokinetics and their clinical significance [J].
Tanaka, E .
JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS, 1999, 24 (05) :339-346
[87]   Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism [J].
Thummel, KE ;
OShea, D ;
Paine, MF ;
Shen, DD ;
Kunze, KL ;
Perkins, JD ;
Wilkinson, GR .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1996, 59 (05) :491-502
[88]   Enzyme-catalyzed processes of first-pass hepatic and intestinal drug extraction [J].
Thummel, KE ;
Kunze, KL ;
Shen, DD .
ADVANCED DRUG DELIVERY REVIEWS, 1997, 27 (2-3) :99-127
[89]   Clinical pharmacokinetics of mirtazapine [J].
Timmer, CJ ;
Sitsen, JMA ;
Delbressine, LP .
CLINICAL PHARMACOKINETICS, 2000, 38 (06) :461-474
[90]  
Tomkins DM, 1997, J PHARMACOL EXP THER, V280, P1374