Role of pharmacologically active metabolites in drug discovery and development

被引：104

作者：

Fura, A ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Metab & Pharmacokinet, Princeton, NJ 08534 USA

来源：

DRUG DISCOVERY TODAY | 2006年 / 11卷 / 3-4期

关键词：

D O I：

10.1016/S1359-6446(05)03681-0

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Pharmacologically active metabolites can contribute significantly to the overall therapeutic and adverse effects of drugs. Therefore, to fully understand the mechanism of action of drugs, it is important to recognize the role of active metabolites. Active metabolites can also be developed as drugs in their own right. Using illustrative examples, this paper discusses a variety of biotransformation reactions that produce active metabolites and their structure-activity relationships. The paper also describes the role and significance of active metabolites in drug discovery and development, various experimental observations that can be used as indicators of their presence, and methods that can be used to assess their biological activities and contribution to the overall therapeutic and adverse effects of drugs.

引用

页码：133 / 142

页数：10

共 72 条

[1]

ALBANI F, 1984, INT J CLIN PHARM RES, V4, P19

[2] Sulfation of minoxidil by multiple human cytosolic sulfotransferases [J].

Anderson, RJ ;

Kudlacek, PE ;

Clemens, DL .

CHEMICO-BIOLOGICAL INTERACTIONS, 1998, 109 (1-3) :53-67

[3] Drug metabolites in safety testing [J].

Baillie, TA ;

Cayen, MN ;

Fouda, H ;

Gerson, RJ ;

Green, JD ;

Grossman, SJ ;

Klunk, LJ ;

LeBlanc, B ;

Perkins, DG ;

Shipley, LA .

TOXICOLOGY AND APPLIED PHARMACOLOGY, 2002, 182 (03) :188-196

[4] A population approach to enzyme characterization and identification: Application to phenacetin O-deethylation [J].

Belle, DJ ;

Ring, BJ ;

Allerheiligen, SRB ;

Heathman, MA ;

O'Brien, LM ;

Sinha, V ;

Roskos, LK ;

Wrighton, SA .

PHARMACEUTICAL RESEARCH, 2000, 17 (12) :1531-1536

[5] Propafenone and its metabolites preferentially inhibit IKr in rabbit ventricular myocytes [J].

Cahill, SA ;

Gross, GJ .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2004, 308 (01) :59-65

[6] Fluoxetine - A review of its therapeutic potential in the treatment of depression associated with physical illness [J].

Cheer, SM ;

Goa, KL .

DRUGS, 2001, 61 (01) :81-110

[7] The discovery of ezetimibe: A view from outside the receptor [J].

Clader, JW .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (01) :1-9

[8] Association between CYP2C19 genotype and proguanil oxidative polymorphism [J].

Coller, JK ;

Somogyi, AA ;

Bochner, F .

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1997, 43 (06) :659-660

[9] LC-NMR-MS in drug discovery [J].

Corcoran, O ;

Spraul, M .

DRUG DISCOVERY TODAY, 2003, 8 (14) :624-631

[10]

Cusack Barry J, 2004, Am J Geriatr Pharmacother, V2, P274, DOI 10.1016/j.amjopharm.2004.12.005

← 1 2 3 4 5 6 7 8 →