Abstract:
:Although activity of cytochrome P450 isoenzymes (CYPs) plays a major role in the fate of anticancer agents in patients, there are relatively few clinical studies that evaluate drug metabolism with therapeutic outcome. Nevertheless, many clinical reports in various non-oncology fields have shown the dramatic importance of CYP activity in therapeutic efficacy, safety and interindividual variability of drug pharmacokinetics. Moreover, variability of drug metabolism in the liver as well as in cancer cells must also be considered as a potential factor mediating cancer resistance. This review underlines the role of drug metabolism mediated by CYPs in pharmacokinetic variability, drug resistance and safety. As examples, biotransformation pathways of tamoxifen, paclitaxel and imatinib are reviewed. This review emphasises the key role of therapeutic drug monitoring as a complementary tool of investigation to in vitro data. For instance, pharmacokinetic data of anticancer agents have not often been published within subpopulations of patients who show ultra-rapid, extensive or poor metabolism (e.g. due to CYP2D6 and CYP2C19 genotypes). Besides kinetic variability in the systemic circulation, induction of CYP activity may participate in creating drug resistance by speeding up the cancer agent degradation specifically in the target cells. For one cancer agent, various mechanisms of resistance are usually identified within different cell clones. This review also tries to emphasise that drug resistance mediated by CYP activity in cancer cells should be taken into consideration to a greater degree. The unequivocal identification of the metabolising enzymes involved in clinical conditions will eventually allow improvement and individualisation of anticancer agent therapy, i.e. drug dosage and selection. In addition, a more complete understanding of the metabolism of anticancer agents will assist in the prediction of drug-drug interactions, as anticancer agent combinations are becoming more prevalent.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Rochat Bdoi
10.2165/00003088-200544040-00002keywords:
subject
Has Abstractpub_date
2005-01-01 00:00:00pages
349-66issue
4eissn
0312-5963issn
1179-1926pii
4442journal_volume
44pub_type
杂志文章,评审abstract::Following administration of equivalent oral doses (30mg) of either prednisone or prednisolone to 5 patients with chronic active liver disease who had failed to respond to therapy, 5 patients with chronic active liver disease in remission induced by prednisone, and 7 healthy volunteers, corticosteroid concentrations we...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198207050-00005
更新日期:1982-09-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Febuxostat is a xanthine oxidase inhibitor indicated for gout and hyperuricemia. This work investigates potential clinically relevant covariates for febuxostat pharmacokinetics with a special focus on Asian race and bodyweight. METHODS:Febuxostat plasma concentrations from 141 male subjects we...
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journal_title:Clinical pharmacokinetics
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更新日期:2007-01-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-199325060-00008
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199528020-00006
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journal_title:Clinical pharmacokinetics
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abstract:BACKGROUND:Reducing the dose of efavirenz can improve safety, reduce costs, and increase access for patients with HIV infection. According to the World Health Organization, a similar dosing strategy for all patient populations is desirable for universal roll-out; however, it remains unknown whether the 400 mg daily dos...
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journal_title:Clinical pharmacokinetics
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更新日期:1999-04-01 00:00:00
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journal_title:Clinical pharmacokinetics
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
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更新日期:1994-01-01 00:00:00
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doi:10.2165/00003088-200847020-00007
更新日期:2008-01-01 00:00:00
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journal_title:Clinical pharmacokinetics
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更新日期:1994-08-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198713010-00003
更新日期:1987-07-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-200140030-00006
更新日期:2001-01-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-200443140-00004
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Abemaciclib, a dual inhibitor of cyclin-dependent kinases 4 and 6, has demonstrated clinical activity in a number of different cancer types. The objectives of this study were to characterize the pharmacokinetics of abemaciclib in cancer patients using population pharmacokinetic (popPK) modelin...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,多中心研究
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更新日期:2018-03-01 00:00:00
abstract::Mifepristone is a steroidal antiprogestin and antiglucocorticoid acting at the receptor level. The aromatic dimethylaminophenyl side chain in position 11 of the steroid structure is essential for the antagonistic properties of mifepristone. The pharmacokinetics of mifepristone are characterised by rapid absorption, a ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-199733010-00002
更新日期:1997-07-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2002-01-01 00:00:00
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更新日期:2017-07-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198308020-00004
更新日期:1983-03-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
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更新日期:2018-09-01 00:00:00
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journal_title:Clinical pharmacokinetics
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doi:10.2165/00003088-199835020-00003
更新日期:1998-08-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199120010-00002
更新日期:1991-01-01 00:00:00
abstract::Uncertainty exists as to the most suitable pharmacokinetic parameter sets for propofol target-controlled infusions (TCI). The pharmacokinetic parameter sets currently employed are clearly not universally applicable, particularly when patient attributes differ from those of the subjects who participated in the original...
journal_title:Clinical pharmacokinetics
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doi:10.2165/11596980-000000000-00000
更新日期:2012-03-01 00:00:00
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journal_title:Clinical pharmacokinetics
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更新日期:2018-08-01 00:00:00
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journal_title:Clinical pharmacokinetics
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doi:10.2165/00003088-199834050-00003
更新日期:1998-05-01 00:00:00
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journal_title:Clinical pharmacokinetics
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更新日期:2017-10-01 00:00:00
abstract::Since 1989 there has been an exponential introduction of new antiepileptic drugs (AEDs) into clinical practice and these include eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, retigabine (ezogabine), rufinamide, stiripentol, tiagabine, top...
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更新日期:2013-11-01 00:00:00
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journal_title:Clinical pharmacokinetics
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doi:10.2165/00003088-199500291-00006
更新日期:1995-01-01 00:00:00