http://purl.uniprot.org/citations/34480602 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/34480602 | http://www.w3.org/2000/01/rdf-schema#comment | "BackgroundBody surface area (BSA)-based dosing of irinotecan (IR) does not account for its pharmacokinetic (PK) and pharmacodynamic (PD) variabilities. Functional hepatic nuclear imaging (HNI) and excretory/metabolic/PD pharmacogenomics have shown correlations with IR disposition and toxicity/efficacy. This study reports the development of a nonlinear mixed-effect population model to identify pharmacogenomic and HNI-related covariates that impact on IR disposition to support dosage optimization.MethodsPatients had advanced colorectal cancer treated with IR combination therapy. Baseline blood was analysed by Affymetrix DMET™ Plus Array and, for PD, single nucleotide polymorphisms (SNPs) by Sanger sequencing. For HNI, patients underwent 99mTc-IDA hepatic imaging, and data was analysed for hepatic extraction/excretion parameters. Blood was taken for IR and metabolite (SN38, SN38G) analysis on day 1 cycle 1. Population modelling utilised NONMEM version 7.2.0, with structural PK models developed for each moiety. Covariates include patient demographics, HNI parameters and pharmacogenomic variants.ResultsAnalysis included (i) PK data: 32 patients; (ii) pharmacogenomic data: 31 patients: 750 DMET and 22 PD variants; and (iii) HNI data: 32 patients. On initial analysis, overall five SNPs were identified as significant covariates for CLSN38. Only UGT1A3_c.31 T > C and ABCB1_c.3435C > T were included in the final model, whereby CLSN38 reduced from 76.8 to 55.1%.ConclusionThe identified UGT1A3_c.31 T > C and ABCB1_c.3435C > T variants, from wild type to homozygous, were included in the final model for SN38 clearance."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.org/dc/terms/identifier | "doi:10.1007/s00228-021-03206-w"xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "Liu Z."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "Link E."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "Martin J.H."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "Michael M."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "Thompson M."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "Campbell I."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "Crowley S."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "Matera A."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "Price T."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "Jefford M."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "Hicks R.J."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "Cullinane C."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "Karapetis C.S."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "Liauw W."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "McLachlan S.A."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "Burge M.E."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "Beale P.J."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/author | "Hatzimihalis A."xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/name | "Eur J Clin Pharmacol"xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/pages | "53-64"xsd:string |
http://purl.uniprot.org/citations/34480602 | http://purl.uniprot.org/core/title | "Evaluation of pharmacogenomics and hepatic nuclear imaging-related covariates by population pharmacokinetic models of irinotecan and its metabolites."xsd:string |