Use of metabolic phenotyping in individualized treatment with amonafide
AssigneeMcGill University
InventorBrian Leyland-Jones
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Abstract
The invention relates to the individualization of therapy on the basis of a phenotypic profile of an individual. More specifically, the present invention relates to the use of metabolic phenotyping for the individualization of treatment with the drug, amonafide.
Claims88
A method of characterizing a multi-determinant metabolic phenotype for a class of N-(aryl substituted)-naphthalidimide compounds, wherein a plurality of phenotypic determinants are identified as corresponding to respective metabolic characteristics;
- said method comprising:
- a) administering to an individual a probe substrate specific to metabolic pathway(s) for said class of N-(aryl substituted)-naphthalidimides compounds;
- b) detecting metabolites of said metabolic pathway(s) in a biological sample from said individual in response to said probe substrate;
- and
- c) characterizing respective phenotypic determinants of said multi-determinant metabolic phenotype based on detected metabolites.
A method of using a multi-determinant metabolic phenotype to individualize a treatment regimen for a class of N-(aryl substituted)-naphthalidimide compounds for an individual, wherein the multi-determinant metabolic phenotype of said individual is determined;
- a safe and therapeutically effective dose of said said class of N-(aryl substituted)-naphthalidimide compoundstreatment is determined and/or selected based on said multi-determinant metabolic phenotype of said individual.
A method of treating an individual having a condition treatable with a class of N-(aryl substituted)-naphthalidimide compounds, with a class of N-(aryl substituted)-naphthalidimide compounds, said method comprising:
- a) determining a multi-determinant metabolic phenotype of said individual;
- and
- b) administering a safe and therapeutically effective dose of said class of N-(aryl substituted)-naphthalidimide compoundsto said individual, wherein said dose has been determined based on a metabolic profile of said individual corresponding to said individual's metabolic phenotype for said class of N-(aryl substituted)-naphthalidimide as represented by said multi-determinant metabolic phenotype.
An assay system for detecting the presence of enzyme-specific metabolites in a biological sample, said sample obtained from an individual treated with a known amount of at least one probe substrate for a class of N-(aryl substituted)-naphthalidimide compounds, specific for metabolic pathways of said metabolites, said assay comprising:
- a) means for receiving said biological sample, including a plurality of affinity complexation agents contained therein;
- b) means for detecting presence of said enzyme-specific metabolites bound to said affinity complexation agents;
- and
- c) means for quantifying ratios of said metabolites to provide corresponding phenotypic determinants;
- wherein said phenotypic determinants provide a metabolic phenotypic profile of said individual.
A method of using an enzyme-specific assay for the individualization of treatment with a class of N-(aryl substituted)-naphthalidimide compounds, which comprises:
- a) conducting said assay to identify phenotypic determinants in a biological sample obtained from an individual treated with a probe substrate for said class of N-(aryl substituted)-naphthalidimide compounds;
- b) determining a rate of drug metabolism according to said determinants;
- and
- c) determining and/or selecting a safe and therapeutically effective dose of said class of N-(aryl substituted)-naphthalidimide compoundsfor said individual based on said rate.
A method of screening a plurality of individuals for participation in a drug treatment trial assessing the therapeutic effect of a class of N-(aryl substituted)-naphthalidimide compounds, said method comprising:
- a) selecting individuals having a metabolic phenotype characterized as effective for metabolizing said class of N-(aryl substituted)-naphthalidimide compounds.
A method of screening a plurality of individuals for treatment with a class of N-(aryl substituted)-naphthalidimide compounds, said method comprising:
- a) genotyping said individuals to identify individuals lacking at least one allelic variation known to prompt toxicity of said class of N-(aryl substituted)-naphthalidimide compounds;
- and
- b) selecting individuals having a metabolic phenoytpe characterized as effective for metabolizing said class of N-(aryl substituted)-naphthalidimide compounds.
A method of screening a plurality of individuals for participation in a drug treatment trial assessing the therapeutic effect of a candidate drug treatment, said method comprising:
- a) genotyping each of said individuals to identify individuals lacking at least one allelic variation known to prompt the toxicity of said drug;
- and
- b) characterizing a multi-determinant metabolic phenotype of said identified individuals of step a) to determine each individual's ability to metabolize said drug.
Dependencies are inferred from the claim text.