Abstract:
BACKGROUND:The imatinib trough plasma concentration (C(min)) correlates with clinical response in cancer patients. Therapeutic drug monitoring (TDM) of plasma C(min) is therefore suggested. In practice, however, blood sampling for TDM is often not performed at trough. The corresponding measurement is thus only remotely informative about C(min) exposure. OBJECTIVES:The objectives of this study were to improve the interpretation of randomly measured concentrations by using a Bayesian approach for the prediction of C(min), incorporating correlation between pharmacokinetic parameters, and to compare the predictive performance of this method with alternative approaches, by comparing predictions with actual measured trough levels, and with predictions obtained by a reference method, respectively. METHODS:A Bayesian maximum a posteriori (MAP) estimation method accounting for correlation (MAP-ρ) between pharmacokinetic parameters was developed on the basis of a population pharmacokinetic model, which was validated on external data. Thirty-one paired random and trough levels, observed in gastrointestinal stromal tumour patients, were then used for the evaluation of the Bayesian MAP-ρ method: individual C(min) predictions, derived from single random observations, were compared with actual measured trough levels for assessment of predictive performance (accuracy and precision). The method was also compared with alternative approaches: classical Bayesian MAP estimation assuming uncorrelated pharmacokinetic parameters, linear extrapolation along the typical elimination constant of imatinib, and non-linear mixed-effects modelling (NONMEM) first-order conditional estimation (FOCE) with interaction. Predictions of all methods were finally compared with 'best-possible' predictions obtained by a reference method (NONMEM FOCE, using both random and trough observations for individual C(min) prediction). RESULTS:The developed Bayesian MAP-ρ method accounting for correlation between pharmacokinetic parameters allowed non-biased prediction of imatinib C(min) with a precision of ±30.7%. This predictive performance was similar for the alternative methods that were applied. The range of relative prediction errors was, however, smallest for the Bayesian MAP-ρ method and largest for the linear extrapolation method. When compared with the reference method, predictive performance was comparable for all methods. The time interval between random and trough sampling did not influence the precision of Bayesian MAP-ρ predictions. CONCLUSION:Clinical interpretation of randomly measured imatinib plasma concentrations can be assisted by Bayesian TDM. Classical Bayesian MAP estimation can be applied even without consideration of the correlation between pharmacokinetic parameters. Individual C(min) predictions are expected to vary less through Bayesian TDM than linear extrapolation. Bayesian TDM could be developed in the future for other targeted anticancer drugs and for the prediction of other pharmacokinetic parameters that have been correlated with clinical outcomes.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Gotta V,Widmer N,Montemurro M,Leyvraz S,Haouala A,Decosterd LA,Csajka C,Buclin Tdoi
10.2165/11596990-000000000-00000subject
Has Abstractpub_date
2012-03-01 00:00:00pages
187-201issue
3eissn
0312-5963issn
1179-1926pii
4journal_volume
51pub_type
杂志文章abstract::The pharmacokinetics of oral morphine sulphate as controlled release tablets ('MS-Contin') and solution were compared at steady-state. Plasma morphine concentrations were determined over 24 hours following the last dose of each drug when given in a randomised, crossover fashion to healthy subjects. Radioimmunoassay wa...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-198611060-00006
更新日期:1986-11-01 00:00:00
abstract::Clarithromycin is a semisynthetic macrolide antibiotic, structurally related to erythromycin. It has a more favourable pharmacokinetic profile than erythromycin, thus allowing twice-daily administration and possibly increasing compliance among outpatients. Clarithromycin is well absorbed from the gastrointestinal trac...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
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abstract::Most of the currently available psychotropic drugs form 1 or more active metabolites during in vivo biotransformation in humans and/or animals. In some cases these metabolites are rapidly conjugated and excreted, but in others they attain blood and/or brain concentrations within the same range as, or even higher than,...
journal_title:Clinical pharmacokinetics
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doi:10.2165/00003088-199018060-00002
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abstract:BACKGROUND AND OBJECTIVE:Genetic polymorphisms of cytochrome P450 (CYP) 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) and patient demographic characteristics are responsible for inter-individual differences in warfarin maintenance dosage requirements. At present, however, the factors associate...
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abstract::18 hypertensive patients with a glomerular filtration rate (GFR) between 3.8 and 113ml/min received guanfacine as single intravenous and multiple oral dose treatment. Mean plasma concentrations of guanfacine on the fifth day or oral treatment ranged from 6.5 to 8.6ng/ml in patients with normal renal function (GFR > 90...
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abstract::Despite contributing significantly to the burden of global disease, the translation of new treatment strategies for diseases of the central nervous system (CNS) from animals to humans remains challenging, with a high attrition rate in the development of CNS drugs. The failure of clinical trials for CNS therapies can b...
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abstract::Nintedanib is an oral, small-molecule tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis and patients with advanced non-small cell cancer of adenocarcinoma tumour histology. Nintedanib competitively binds to the kinase domains of vascular endothelial growth factor (VEGF), platelet-de...
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pub_type: 杂志文章,评审
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更新日期:1995-11-01 00:00:00
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更新日期:2007-01-01 00:00:00
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journal_title:Clinical pharmacokinetics
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doi:10.2165/00003088-198106040-00006
更新日期:1981-07-01 00:00:00
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更新日期:2001-01-01 00:00:00
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doi:10.2165/00003088-199630030-00001
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doi:10.2165/00003088-198510060-00004
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abstract::Short-term antimanic therapy with lithium and relapse-repressive, so-called "prophylactic" long-term therapy with lithium, may present clinical problems which demand an understanding of two cardinal properties of this form of therapy--the need to individualise the dose and the recognition that successful therapy invol...
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更新日期:2016-03-01 00:00:00
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journal_title:Clinical pharmacokinetics
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abstract::Carboplatin shares some of the therapeutic advantages of cisplatin, but without a significant incidence of the dose-limiting neurotoxicity and nephrotoxicity which is experienced with cisplatin. However, its use is associated with dose-limiting bone marrow suppression. Carboplatin is present in the blood as 3 distinct...
journal_title:Clinical pharmacokinetics
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doi:10.2165/00003088-199733030-00002
更新日期:1997-09-01 00:00:00
abstract::The combination of artemether and lumefantrine (benflumetol) is a new and very well tolerated oral antimalarial drug effective even against multidrug-resistant falciparum malaria. The artemether component is absorbed rapidly and biotransformed to dihydroartemisinin, and both are eliminated with terminal half-lives of ...
journal_title:Clinical pharmacokinetics
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更新日期:1999-08-01 00:00:00
abstract::The pharmacokinetics and antihypertensive effects of felodipine, a new dihydropyridine calcium channel blocker, were studied in elderly hypertensive patients, 67 to 79 years of age and in young healthy subjects, 20 to 34 years of age following oral administration of 5 mg twice daily to steady-state. A single intraveno...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198814060-00004
更新日期:1988-06-01 00:00:00
abstract::The pharmacokinetics of dothiepin were evaluated in 9 depressed patients following a single oral dose of 75 mg. Blood and plasma concentrations of dothiepin and 2 major metabolites, northiaden and dothiepin S-oxide, were measured by gas chromatography/mass fragmentography. The mean (+/-SD) peak plasma concentrations o...
journal_title:Clinical pharmacokinetics
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更新日期:1983-03-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Recent analysis revealed strong associations between prostate-specific antigen (PSA) dynamics and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) and supported PSA dynamics as bridging surrogacy endpoints for clinical benefit from treatment with abiraterone ace...
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更新日期:2017-01-01 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