摘要:
A pathway for the metabolism of tamoxifen is identified including the activity of at least 2 different isoforms of UGY2B7. This pathway includes isozymes of CYP3A which convert tamoxifen (TAM) to N-desmethyl-TAM, which is then converted to endoxifen by the action of CYP2D6. Once formed, endoxifen may be degraded by at least one isozyme of UGT2B7. Patients that have highly active isoforms of CYP2D6 and slow acting isoforms of UGT2B7 accumulate high levels of endoxifen and are good candidates for treatment with tamoxifen. Also disclosed are methods for screening patients with a high likelihood of benefiting from treatment with tamoxifen. These methods include testing patients for various alleles of genes known to be involved in tamoxifen metabolism and treating patients accordingly.
摘要:
The present invention relates, generally to a method of determining and assessing cytochrome P450 2C19-related (CYP2Cl9) metabolic capacity in an individual mammalian subject via a breath assay, by determining the relative amount of 13CO2 exhaled by the subject upon intravenous or oral administration of a 13C-labeled CYP2C19 substrate compound. The present invention is useful as a non-invasive, in vivo assay for evaluating CYP2C19 enzyme activity in a subject using the metabolite 13CO2 in expired breath, to phenotype individual subjects and to determine the selection, optimal dosage and timing of drug administration.
摘要:
The present invention relates, generally to a method of determining and assessing cytochrome P450 2C19-related (CYP2C19) metabolic capacity in an individual mammalian subject via a breath assay, by determining the relative amount of 13CO2 exhaled by the subject upon intravenous or oral administration of a 13C-labeled CYP2C19 substrate compound. The present invention is useful as anon-invasive, in vivo assay for evaluating CYP2C19 enzyme activity in a subject using the metabolite 13CO2 in expired breath, to phenotype individual subjects and to determine the selection, optimal dosage and timing of drug administration.
摘要:
The present invention relates, generally to a method of determining and assessing cytochrome P450 2C19-related (CYP2Cl9) metabolic capacity in an individual mammalian subject via a breath assay, by determining the relative amount of 13CO2 exhaled by the subject upon intravenous or oral administration of a 13C-labeled CYP2C19 substrate compound. The present invention is useful as a non-invasive, in vivo assay for evaluating CYP2C19 enzyme activity in a subject using the metabolite 13CO2 in expired breath, to phenotype individual subjects and to determine the selection, optimal dosage and timing of drug administration.