Abstract:
PURPOSE:Our aim was to develop an optimal sampling strategy for the description of the pharmacokinetics of rubitecan and its active metabolite 9-aminocamptothecin (9-AC) for use in phase II/III studies with oral rubitecan administered in a daily times five schedule. METHODS:Concentration-time data of rubitecan and 9-AC were obtained from 14 patients who had received 1.5 mg/m(2) per day rubitecan orally. Population pharmacokinetic analysis of both the parent and the metabolite was performed using the nonlinear mixed effect modelling program (NONMEM). Optimal sampling points were selected on the basis of the assessed population pharmacokinetic parameters using a D-optimality algorithm. RESULTS:The pharmacokinetics of both rubitecan and 9-AC were adequately described with a one-compartment model. The absorption rate constant, apparent volume of distribution and apparent clearance of rubitecan were 0.81 h(-1), 50 l and 1.7 l/h, respectively. For 9-AC the corresponding values of the apparent volume of distribution and the elimination rate constant were 51 l and 0.102 h(-1). Interindividual variability of the pharmacokinetic parameters ranged from 38% to 49%. For the first dose, optimal sampling points were 1, 3, 5, 8 and 24 h after dosing. Monte Carlo simulations indicated that the sampling schedule produced parameter estimates which were unbiased and precise. CONCLUSIONS:An optimal sampling schedule was derived which allowed assessment of the pharmacokinetic parameters of both the parent compound and its metabolite 9-AC after oral administration of rubitecan.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Schoemaker NE,Mathôt RA,Schöffski P,Rosing H,Schellens JH,Beijnen JHdoi
10.1007/s00280-002-0516-5keywords:
subject
Has Abstractpub_date
2002-12-01 00:00:00pages
514-7issue
6eissn
0344-5704issn
1432-0843journal_volume
50pub_type
临床试验,杂志文章,随机对照试验abstract:PURPOSE:The purpose of this study was to assess the therapeutic and toxicological effects of cesium chloride (CsCl) administration in mice bearing prostate cancer tumors. METHODS:Three CsCl dose titration studies were completed in tumor-bearing and non-tumor-bearing athymic nude mice. All mice were administered either...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0429-4
更新日期:2007-11-01 00:00:00
abstract::In this review of the management of invasive carcinoma of the bladder the results of primary and systemic therapies are evaluated in the light of the natural history of the disease. The clinical and pathological causes of treatment failure are assessed in an attempt to identify new approaches that may be used in the f...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/BF00254978
更新日期:1979-01-01 00:00:00
abstract::The metabolic disposition and pharmacokinetics of TNP-470 were investigated in rhesus monkeys following intravenous administration of 5 mg/kg of [3H]-TNP-470. Rapid and extensive metabolism of parent drug to six metabolites occurred as demonstrated by the absence of unchanged drug in plasma and urine at time points as...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050458
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:Some clinical studies on etoposide (Eto) have shown marked schedule dependency of the effect (starting at about 1 mg/l) and toxicity (over about 10 mg/l) whereas other studies have not confirmed these results. What are the conclusions we can draw from these inconsistent results when developing new low-dose (LD)...
journal_title:Cancer chemotherapy and pharmacology
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doi:10.1007/s00280-001-0418-y
更新日期:2002-04-01 00:00:00
abstract:PURPOSE:Abiraterone acetate (AA) was recently approved for castration-resistant prostate cancer in Japan. Two phase 1 studies were conducted to assess the pharmacokinetics of abiraterone after single-dose administration in Japanese healthy men and to evaluate the effects of food timing on abiraterone pharmacokinetics a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/s00280-014-2616-4
更新日期:2015-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
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更新日期:2009-02-01 00:00:00
abstract:PURPOSE:Gemcitabine/cisplatin combination therapy has been the standard palliative chemotherapy for patients with advanced biliary tract cancer (BTC). We aimed to evaluate the efficacy and safety of adding S-1 to gemcitabine/cisplatin combination therapy for patients with advanced BTC. METHODS:Patients with histologic...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
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abstract::A four-fold (P less than 0.001) mean increase in iron levels was found in 18 patients (a total of 36 courses of therapy) with ovarian cancer at the end of a 5-day course of cisplatin (40 mg/m2 per day every 4-5 weeks). The kinetics of these modifications began very early (24-48 h after initiation of therapy): they rea...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
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journal_title:Cancer chemotherapy and pharmacology
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abstract:PURPOSE:The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib (ZD1839, Iressa) is approved for cancer treatment. We investigated whether gefitinib treatment can enhance human EGF (hEGF) uptake in vitro, thereby increasing the potential of hEGF as a vehicle for EGFR-targeted therapy. METHODS:W...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,meta分析
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更新日期:2009-06-01 00:00:00
abstract:PURPOSE:The purpose of this study was to evaluate the expression of ser-miRNAs at different periods during treatment and analyze their relationship with therapeutic response and prognosis in HER2-positive breast cancer patients receiving neoadjuvant chemotherapy combined with trastuzumab (NCCT). METHODS:Venous blood w...
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更新日期:2019-11-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
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doi:10.1007/s00280-005-1014-3
更新日期:2005-12-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
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abstract::The activity of CD437¿6-[3-(1-adamantyl)-4 hydroxyphenyl]-2-naphthalene carboxylic acid¿, a relatively selective activator of RAR-gamma, was evaluated against four human ovarian-carcinoma cell lines : PE01, PE04 (a Pt-resistant in vivo-derived counterpart of PE01), PE01CDDP (a Pt-resistant in vitro-derived model of PE...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
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abstract:PURPOSE:The observation that the orphan drug dichloroacetate (DCA) selectively promotes mitochondria-regulated apoptosis and inhibits tumour growth in preclinical models by shifting the glucose metabolism in cancer cells from anaerobic to aerobic glycolysis attracted not only scientists', clinicians' but also patients'...
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
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更新日期:2007-01-01 00:00:00
abstract::When tumor cell density increases, the cytotoxic activity of certain anticancer agents, such as vincristine (VCR) and doxorubicin (DXR), progressively decreases. This phenomenon is termed the inoculum effect. Since VCR and DXR are less active in an acidic environment, we questioned whether the inoculum effects could h...
journal_title:Cancer chemotherapy and pharmacology
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
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更新日期:1998-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
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更新日期:2015-03-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
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更新日期:2005-02-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2468-y
更新日期:2014-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:2017-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2011-08-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2005-10-01 00:00:00
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pub_type: 杂志文章,随机对照试验
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更新日期:2018-07-01 00:00:00