Pharmacokinetic Modeling of Plasma and Cerebrospinal Fluid Methotrexate after High-Dose Intravenous Infusion in Children

Chatelut, Étienne; Roché, Henri; Plusquellec, Y.; Peyrille, F.; Biasi, J. De; Pujol, André; Canal, Pierre; Houin, Georges

doi:10.1002/jps.2600800804

Cited by 17 publications

(4 citation statements)

References 10 publications

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“…The AUC(%) cerebrospinal fluid/serum ratio obtained provides an indication of the amount of methotrexate delivered to the cerebrospinal fluid, which is significantly higher after blood‐brain barrier disruption treatment than by systemic administration of the drug. In a pharmacokinetic study performed in children with brain tumors who were treated with intravenous high‐dose methotrexate, the cerebrospinal fluid/plasma ratio ranged between 0.9% to 3.38% 18 . In this study the cerebrospinal fluid/serum ratio [AUC(%)] after blood‐brain barrier disruption was three to four times greater than the ratios observed after systemic administration.…”

Section: Discussionmentioning

confidence: 60%

Pharmacokinetics of methotrexate in cerebrospinal fluid and serum after osmotic blood-brain barrier disruption in patients with brain lymphoma

Zylber‐Katz

Gomori²,

Schwartz³

et al. 2000

Clinical Pharmacology & Therapeutics

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Section: Discussionmentioning

confidence: 60%

Pharmacokinetics of methotrexate in cerebrospinal fluid and serum after osmotic blood-brain barrier disruption in patients with brain lymphoma

Zylber‐Katz

Gomori²,

Schwartz³

et al. 2000

Clinical Pharmacology & Therapeutics

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“…A number of models have been developed in an attempt to predict the concentrations of active metabolites in tumour cells [26, 30]. These models have been developed with knowledge from in vitro experiments and animal tumour models [31, 32].…”

Section: Systemic Pharmacology Analytical Methodology and Pharmacokimentioning

confidence: 99%

Recent developments in the clinical pharmacology of classical cytotoxic chemotherapy

Boddy

2006

Brit J Clinical Pharma

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Advances in analytical methods, imaging techniques and an increased understanding of the influence of pharmacogenetic factors have added to our knowledge of the pharmacology of many chemotherapeutic agents. Extending the use of these approaches to pharmacodynamic end-points, together with the application of population-based modelling techniques, offers the potential to develop truly individualized therapy in the future.The concept that major improvements in cancer treatment could come about simply by increasing our knowledge of the systemic pharmacology of cytotoxic drugs has not been borne out by many of the studies performed in the last 20 years. Data on plasma concentrations of drug and metabolites have allowed the successful development of a number of novel agents and has been useful in guiding dosage regimens and the design of novel prodrugs. However, the goal of using clinical pharmacology to individualize therapy in order to optimize the treatment of each tumour in every patient has not been achieved. Clinical pharmacology studies continue to generate more detailed data on classical cytotoxic drugs. However, to date only for carboplatin [1,2] and possibly for methotrexate [3] and etoposide [4] is there any rationale for individualized dosing based solely on a knowledge of systemic pharmacology. In this review, I will focus on the methodological and conceptual developments that have augmented our understanding of 'classical cytotoxic' drugs, beyond simple measurements of total drug or metabolites in plasma. These developments include new technologies, integration of genetic and other biological determinants of pharmacology and novel statistical and data analysis approaches.

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“…A peripheral compartment may also be related to a tissue or portion of tissue with particular distribution kinetics. In this sense, this type of model has been widely applied to intravenously administered drugs diffusing to the central nervous system, such as morphine or methotrexate [70,71], or even models with a broad number of compartments, each representing an organ [72].…”

Section: Multi-compartment Modelmentioning

confidence: 99%

Drug Tissue Distribution: Study Methods and Therapeutic Implications

Lanao¹,

Fraile²

2005

CPD

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Current interest in studies on tissue distribution stems from the limited capacity to predict tissue concentrations and the pharmacological response from plasma drug levels, and from the limitations - both methodological and deontological- involved in doing so, especially in humans. In this review we carry out a comparative analysis of the methods used for studying tissue distribution, placing special focus on recently developed non-invasive methods for the research of tissue distribution in humans, such as positron emission tomography and nuclear magnetic resonance spectroscopy. We describe the strategies of tissue distribution pharmacokinetic analysis that have evolved from analysis based on compartment and physiological models to analyses based on spatial and fractal models and, mainly, pharmacokinetic-pharmacodynamic models. Model-independent analysis based on the use of mean transit times or deconvolution strategies has become a good alternative for the pharmacokinetic analysis of tissue distribution. The need to increase the selectivity of many drugs justifies the desire to gain further insight into the design of new analogues prodrugs and carrier systems that will guarantee the specific delivery of a given drug to a particular organ or tissue, optimising the response. In silico models for drug distribution have become a helpful tool in drug discovery and development. The therapeutic implications of drug tissue distribution are also analysed, special reference being made to antiretroviral therapy and antitumoural gene therapy, among others.

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Pharmacokinetic Modeling of Plasma and Cerebrospinal Fluid Methotrexate after High-Dose Intravenous Infusion in Children

Cited by 17 publications

References 10 publications

Pharmacokinetics of methotrexate in cerebrospinal fluid and serum after osmotic blood-brain barrier disruption in patients with brain lymphoma

Pharmacokinetics of methotrexate in cerebrospinal fluid and serum after osmotic blood-brain barrier disruption in patients with brain lymphoma

Recent developments in the clinical pharmacology of classical cytotoxic chemotherapy

Drug Tissue Distribution: Study Methods and Therapeutic Implications

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