Pharmacokinetics and pharmacogenetics of the MEK1/2 inhibitor, selumetinib, in Asian and Western healthy subjects: a pooled analysis.
Purpose: Emerging data on selumetinib, a MEK1/2 inhibitor in clinical development, suggest a possible difference in pharmacokinetics (PK) between Japanese and Western patients. This pooled analysis sought to assess the effect of ethnicity on selumetinib exposure in healthy Western and Asian subjects...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 73; no. 6; pp. 717 - 727 |
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| Autores principales: | , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
Jun2017
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=122940977&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 122940977 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Jun2017 vid: 73 iid: 6 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 122940977 122940977 144008340 122940977 10.1007/s00228-017-2217-3 122940977 ppf: 717 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Pharmacokinetics and pharmacogenetics of the MEK1/2 inhibitor, selumetinib, in Asian and Western healthy subjects: a pooled analysis. aug: au: Dymond, Angela Elks, Cathy Martin, Paul Carlile, David Mariani, Gabriella Lovick, Susan Huang, Yifan Lorch, Ulrike Brown, Helen So, Karen affil: AstraZeneca, Personalised Healthcare & Biomarkers, Innovative Medicines and Early Development Biotech Unit , Darwin Building, 310 Cambridge Science Park, Milton Road Cambridge CB4 0WG UK sug: subj: Pharmacokinetics Pharmacogenetics Protein Kinase Inhibitors Classification Drug Therapy Evaluation Human Asia Geographic Locations Ethnic Groups ab: Purpose: Emerging data on selumetinib, a MEK1/2 inhibitor in clinical development, suggest a possible difference in pharmacokinetics (PK) between Japanese and Western patients. This pooled analysis sought to assess the effect of ethnicity on selumetinib exposure in healthy Western and Asian subjects, and to identify any association between genetic variants in the UGT1A1, CYP2C19 and ABCG2 genes and observed differences in selumetinib PK. Methods: A pooled analysis of data from ten Phase I studies, one in Asian subjects (encompassing Japanese, non-Japanese Asian and Indian Asian subjects) and nine in Western subjects, was conducted. Key findings were derived from the collective exposure data across doses of 25, 35, 50 and 75 mg selumetinib; primary variables were dose-normalized AUC and C. Results: PK data from 308 subjects (10 studies) were available for the pooled analysis; genetic data from 87 subjects (3 studies) were available for the pharmacogenetic analysis. Dose-normalized AUC and C were 35% (95% CI: 25-47%) and 39% (95% CI: 24-56%) higher in the pooled Asian group, respectively, compared with Western subjects. PK exposure parameters were similar between the Japanese, non-Japanese Asian and Indian groups. There was no evidence that the polymorphisms assessed in the genes UGT1A1, CYP2C19 and ABCG2 account for observed PK differences. Conclusions: Selumetinib exposure was higher in healthy Asian subjects compared with Western subjects, and these data provide valuable insight for clinicians to consider when treating patients of Asian ethnicity with selumetinib. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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