Abstract:
:The combination of hepatic artery infusion (HAI) of irinotecan, 5-fluorouracil and oxaliplatin with intravenous cetuximab has safely achieved prolonged survival in colorectal cancer patients with extensive liver metastases and prior treatment. Systemic exposure to the drugs or their main metabolites was determined during the first course of chronomodulated triplet HAI in 11 patients and related to toxicities after one or three courses. Consistent trends were found between the area under the plasma concentration-time curve (AUC) values of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN38; a bioactive metabolite), total oxaliplatin and platinum ultrafiltrate (P-UF), on the one hand, and subsequent leukopenia severity, on the other hand. Moreover, the maximum plasma concentration (C max) and the AUC of P-UF significantly predicted grades of diarrhoea (p = 0.004 and 0.017, respectively) and anaemia (p = 0.001 and 0.008, respectively) after the first course. Systemic drug exposure helps explain both the adverse events and the low rate of extrahepatic progression-a usual drawback of HAI chemotherapy-thus supporting upfront testing of the regimen. Systems optimization of chronomodulated HAI delivery could further reduce adverse events.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Lévi F,Karaboué A,Etienne-Grimaldi MC,Paintaud G,Focan C,Innominato P,Bouchahda M,Milano G,Chatelut Edoi
10.1007/s40262-016-0431-2subject
Has Abstractpub_date
2017-02-01 00:00:00pages
165-177issue
2eissn
0312-5963issn
1179-1926pii
10.1007/s40262-016-0431-2journal_volume
56pub_type
临床试验,杂志文章,多中心研究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
abstract:BACKGROUND AND OBJECTIVE:Elagolix is an oral, non-peptide, gonadotropin-releasing hormone receptor antagonist. It is approved for the treatment of moderate-to-severe pain associated with endometriosis and is being investigated for the treatment of heavy menstrual bleeding associated with uterine fibroids. Use of low-do...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-020-00921-y
更新日期:2021-01-01 00:00:00
abstract::Warfarin, like all the 4-hydroxycoumarin compounds, has an asymmetric carbon atom. The clinically available warfarin preparations consist of a racemic mixture of equal amounts of 2 distinct S and R isomers, the former being 4-times more potent as anticoagulant and more susceptible to drug interaction. Warfarin is high...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199630040-00003
更新日期:1996-04-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Tegafur is an oral fluorouracil prodrug used in the treatment of colorectal cancer. The aim of this phase II, crossover, bioequivalence study was to compare the pharmacokinetics (primary objective) and tolerability (secondary objective) of tegafur-uracil (UFT) given as three daily doses (tid, r...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.2165/00003088-200746110-00003
更新日期:2007-01-01 00:00:00
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...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200544040-00002
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Buprenorphine has been shown to be effective in treating infants with neonatal opioid withdrawal syndrome. However, an evidence-based buprenorphine dosing strategy has not been established in the treatment of neonatal opioid withdrawal syndrome because of a lack of exposure-response data. The a...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-020-00939-2
更新日期:2020-09-17 00:00:00
abstract::Beta-adrenoceptor antagonists are among the most commonly prescribed classes of drugs. They are indicated for the treatment of diseases such as hypertension and angina pectoris, in which long term therapy is often required. Since many beta-adrenoceptor antagonists have short plasma elimination half-lives, divided dail...
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
abstract:INTRODUCTION:Bruton tyrosine kinase (BTK) is a key component of B-cell receptor signalling, critical for cell proliferation. Acalabrutinib, a selective, covalent BTK inhibitor, recently received an accelerated approval in relapsed/refractory mantle cell lymphoma. This analysis characterized the population pharmacokinet...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s40262-018-0725-7
更新日期:2019-05-01 00:00:00
abstract:INTRODUCTION:Neglected tropical diseases (NTDs) affect more than one billion people, mainly living in developing countries. For most of these NTDs, treatment is suboptimal. To optimize treatment regimens, clinical pharmacokinetic studies are required where they have not been previously conducted to enable the use of ph...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-016-0467-3
更新日期:2017-06-01 00:00:00
abstract::A pharmacokinetic study of alpha 1-antitrypsin (ATT) was performed in 2 groups of homozygous PiZ-deficient patients (treated and untreated) and 1 group of healthy volunteers. The distribution of the 131I-labelled protein corresponds to a 3-compartment model. The intravenously administered protein diffused quickly to t...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-199223020-00007
更新日期:1992-08-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Oral levodopa-carbidopa (LC-oral) treatment in advanced Parkinson's disease (PD) is associated with motor complications due to large fluctuations in levodopa plasma concentrations. Levodopa-carbidopa intestinal gel (LCIG) provides individualized continuous levodopa-carbidopa delivery through in...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s40262-015-0265-3
更新日期:2015-09-01 00:00:00
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...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-018-0642-9
更新日期:2018-11-01 00:00:00
abstract::Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel approach for the management of type 2 diabetes mellitus. They have proven their efficacy in reducing glycated haemoglobin...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-013-0128-8
更新日期:2014-04-01 00:00:00
abstract:BACKGROUND:Enzyme replacement therapy (ERT) is currently the standard treatment for patients with Gaucher disease type I (GD1), but the pharmacokinetics have hardly been studied. This study aimed to quantify in vivo enzyme activity in peripheral leukocytes from patients receiving long-term treatment with imiglucerase o...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-016-0387-2
更新日期:2016-09-01 00:00:00
abstract::The present article should be read in conjunction with the original review published in the Journal in 1983. There is no new information of major significance about the pharmacokinetics of levonorgestrel, norethisterone (norethindrone) or ethinylestradiol, although it has been shown that the concentrations of these ho...
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::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...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-013-0087-0
更新日期:2013-11-01 00:00:00
abstract::In the original publication, Page 3, Sect. 4.3, the first sentence was incorrectly published. ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,已发布勘误
doi:10.1007/s40262-018-0633-x
更新日期:2018-05-01 00:00:00
abstract::Pegfilgrastim is a sustained-duration form of filgrastim, a recombinant methionyl form of human granulocyte colony-stimulating factor (G-CSF), to which a 20 kDa polyethylene glycol molecule is covalently bound to the N-terminal methionine residue. Similar to filgrastim, pegfilgrastim increases the proliferation and d...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/11586040-000000000-00000
更新日期:2011-05-01 00:00:00
abstract:BACKGROUND:Ovarian cancer is the leading cause of gynaecological cancer-related death in Western countries. Intraperitoneal (IP) peroperative chemotherapy is an interesting therapeutic option. However, very few data are available regarding pharmacokinetics and especially population pharmacokinetics. PATIENTS AND METHO...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200948030-00003
更新日期:2009-01-01 00:00:00
abstract::With the aging population and its rapidly increasing prevalence, dementia has become an important public health concern in developed and developing countries. To date, the pharmacological treatment is symptomatic and based on the observed neurotransmitter disturbances. The four most commonly used drugs are donepezil, ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-013-0038-9
更新日期:2013-04-01 00:00:00
abstract:OBJECTIVE:To investigate the effect of concomitant administration of dairy products on the pharmacokinetics and tolerability of moxifloxacin. DESIGN:This was a single-centre, randomised, controlled, nonblinded, 2-way crossover study in healthy volunteers. PARTICIPANTS:12 healthy men (aged 25 to 46 years) were enrolle...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-200140001-00005
更新日期:2001-01-01 00:00:00
abstract::Although individualised antihypertensive therapy is widely recommended, prospective methods for optimising treatment are hampered by the paucity of basic information about dose-plasma concentration-response relationships for commonly used drugs. Concentration-effect analysis has been applied to a number of therapeutic...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199426060-00005
更新日期:1994-06-01 00:00:00
abstract::Various pharmacokinetic models, both simple and complex, have been developed to describe the way in which the rate of hepatic elimination of drugs depends on hepatic blood flow, hepatic intrinsic clearance and unbound fraction of drug in blood. A model is necessary because it is not possible to measure the average blo...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199018010-00004
更新日期:1990-01-01 00:00:00
abstract:OBJECTIVE:To determine the multiple dose pharmacokinetics of a new extended release (ER) capsule formulation of tolterodine, compared with the existing immediate release (IR) tablet, in healthy volunteers. DESIGN:Nonblind, randomised, 2-way crossover trial. PARTICIPANTS:19 healthy volunteers (7 females, 12 males), me...
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
abstract::The safety profile of any pharmacological agent is defined on the basis of its toxicity, tolerability and potential for pharmacokinetic and/or pharmacodynamic interactions with other compounds, which may belong to the same or to a different pharmacological class. Drug-drug interactions are important in clinical practi...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199835020-00003
更新日期:1998-08-01 00:00:00
abstract::Etodolac is a chiral nonsteroidal anti-inflammatory drug (NSAID) that is marked as the racemate. Currently, the drug is available in several countries for the treatment of arthritis and the alleviation of pain. Etodolac possesses several unique disposition features mainly due to its stereoselective pharmacokinetics. I...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199426040-00003
更新日期:1994-04-01 00:00:00
abstract::A substantial proportion of migraine patients have gastric stasis and suffer severe nausea and/or vomiting during their migraine attack. This may lead to erratic absorption from the gastrointestinal tract and make oral treatment unsatisfactory. For such patients, an intranasal formulation may be advantageous. Sumatrip...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200241110-00002
更新日期:2002-01-01 00:00:00
abstract::The use of liposomal carriers and the modification of therapeutic molecules through the attachment of poly(ethylene glycol) [PEG] moieties ('pegylation') are the most common approaches for enhancing the delivery of parenteral agents. Although 'classical' liposomes (i.e. phospholipid bilayer vehicles) have been effecti...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200140070-00005
更新日期:2001-01-01 00:00:00
abstract::Few of the articles published on antibiotics and pregnancy are concerned with pharmacokinetics. It is particularly difficult to evaluate possible alterations in pharmacokinetic parameters that may be due to pregnancy. Most data available have been obtained in connection with abortion or delivery. Such data may not be ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-197904040-00003
更新日期:1979-07-01 00:00:00
abstract::The plasma protein binding of drugs, particularly those that are highly bound, may have significant clinical implications. Although protein binding is a major determinant of drug action, it is only one of a myriad of factors that influence drug disposition. The extent of protein binding is a function of drug and prote...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200038030-00005
更新日期:2000-03-01 00:00:00