Abstract:
PURPOSE:To evaluate the plasma protein binding and pharmacokinetics of prednisolone during therapeutic use in children with acute lymphoblastic leukemia (ALL) using the population approach. METHODS:A two-compartment pharmacokinetic model was used to describe data from 23 children with ALL (aged 2-15 years). Prednisolone (60 mg/m(2) per day in three divided doses) was administered both orally and intravenously, and samples were obtained on several days during the initial 5 weeks of remission induction therapy. Unbound plasma concentrations ( n=288) were determined by HPLC and ultrafiltration. Nonlinear mixed-effects modeling (WinNonMix version 2.0.1) was used to estimate the pharmacokinetic parameters, to identify significant covariates, and to estimate the protein binding parameters. RESULTS:Prednisolone showed complete oral bioavailability. The median unbound clearance (32 l/h per m(2)) was lower, and the half-life (3.6 h) longer than previously reported in childhood ALL. Body weight was a significant covariate for the central and peripheral volumes of distribution resulting in interindividual variabilities of 50% and 42%. Including body surface area as a covariate for clearance decreased the interindividual variability to 14%. The estimated areas under the unbound plasma concentration-time curves showed less than twofold variation among patients, and a residual variability of 20% indicated that the pharmacokinetic parameters remained stable during induction therapy. The estimated protein binding parameters were comparable to, but slightly lower than, previously published values and independent of the albumin concentration. CONCLUSIONS:The study showed complete oral bioavailability, a lower unbound clearance and a longer half-life for prednisolone than previously reported in childhood ALL. Plasma protein binding was independent of the albumin concentration. Due to the small inter- and intraindividual variations in the pharmacokinetic parameters, body surface area-based dosing is sufficient to obtain similar systemic exposure among patients.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Petersen KB,Jusko WJ,Rasmussen M,Schmiegelow Kdoi
10.1007/s00280-003-0602-3keywords:
subject
Has Abstractpub_date
2003-06-01 00:00:00pages
465-73issue
6eissn
0344-5704issn
1432-0843journal_volume
51pub_type
临床试验,杂志文章abstract:PURPOSE:The aim of this study was to evaluate a phenotypic cell panel with tumor cells from various patients and normal cells for preclinical profiles of antitumor efficacy and toxicity of anticancer drugs. METHODS:The antitumor activity of fourteen anticancer drugs was tested in over one hundred tumor samples from pa...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1746-1
更新日期:2012-03-01 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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更新日期:2008-09-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050614
更新日期:1997-01-01 00:00:00
abstract::Anthracyclines are important antitumor agents used in the treatment of solid tumors, lymphomas, and acute lymphoblastic as well as myelocytic leukemias. The clinical utility of agents such as doxorubicin and daunorubicin and their well-characterized cardiotoxicity have prompted many efforts to develop analogs that ret...
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
doi:10.1007/BF00257519
更新日期:1985-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0858-8
更新日期:2009-05-01 00:00:00
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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,评审
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更新日期:2014-10-01 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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更新日期:1996-01-01 00:00:00
abstract:PURPOSE:To evaluate the effect of front-line chemotherapy on CK-19mRNA+ circulating tumor cells (CTCs) and their relevance in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS:The presence of CK-19mRNA+ CTCs was assessed using a real-time RT-PCR assay in 298 previously untreated patients with MBC befo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
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更新日期:2014-12-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00578556
更新日期:1980-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The optimal chemotherapeutic protocol for the treatment of esophageal cancer has not yet been established. A dose-escalation study of docetaxel combined with cisplatin and 5-fluorouracil (5-FU) was performed to determine the optimal dose in patients with advanced esophageal squamous cell carcinom...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1447-1
更新日期:2010-11-01 00:00:00
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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
pub_type: 杂志文章
doi:10.1007/s00280-007-0670-x
更新日期:2008-10-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-017-3342-5
更新日期:2017-07-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00258297
更新日期:1979-01-01 00:00:00
abstract::Methylene blue (MB) is a phenothiazine with radio and photosensitizing properties and anti-tumoral activity. Our group has shown that MB was capable of inhibiting the in vitro growth of erythroleukemic cells with multidrug resistance (MDR). However, there are no studies comparing the cytotoxicity of this molecule for ...
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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journal_title:Cancer chemotherapy and pharmacology
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更新日期:1979-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
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更新日期:2015-09-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
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更新日期:2018-03-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
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更新日期:1981-01-01 00:00:00
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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:2017-02-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
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更新日期:2006-11-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
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更新日期:2005-04-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
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更新日期:2016-04-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
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更新日期:1999-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
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更新日期:2002-12-01 00:00:00