Publications
Detailed Information
Osimertinib Western and Asian clinical pharmacokinetics in patients and healthy volunteers: implications for formulation, dose, and dosing frequency in pivotal clinical studies
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Planchard, David | - |
dc.contributor.author | Brown, Kathryn H. | - |
dc.contributor.author | Kim, Dong-Wan | - |
dc.contributor.author | Kim, Sang-We | - |
dc.contributor.author | Ohe, Yuichiro | - |
dc.contributor.author | Felip, Enriqueta | - |
dc.contributor.author | Leese, Philip | - |
dc.contributor.author | Cantarini, Mireille | - |
dc.contributor.author | Vishwanathan, Karthick | - |
dc.contributor.author | Jaenne, Pasi A. | - |
dc.contributor.author | Ranson, Malcolm | - |
dc.contributor.author | Dickinson, Paul A. | - |
dc.date.accessioned | 2020-04-27T11:12:42Z | - |
dc.date.available | 2020-04-27T11:12:42Z | - |
dc.date.created | 2018-08-28 | - |
dc.date.issued | 2016-04 | - |
dc.identifier.citation | Cancer Chemotherapy and Pharmacology, Vol.77 No.4, pp.767-776 | - |
dc.identifier.issn | 0344-5704 | - |
dc.identifier.other | 47394 | - |
dc.identifier.uri | https://hdl.handle.net/10371/165290 | - |
dc.description.abstract | Osimertinib (AZD9291) 80 mg once daily is approved by the US FDA for the treatment of patients with metastatic EGFR T790M-positive NSCLC whose disease has previously progressed on EGFR-TKI therapy. Osimertinib PK was evaluated to define the dose and dosing interval, whether a fixed-dosing approach can be used globally, and the impact of formulation and food on exposure. AURA (NCT01802632): single- and multiple-dose PK of osimertinib (20-240 mg daily) was determined in patients with advanced NSCLC. Bioavailability study (NCT01951599): single-dose PK of osimertinib (20 mg) was determined in healthy volunteers with administration of capsule, solution, or tablet formulations fasted, and as a tablet in the fed and fasted state. Osimertinib was slowly absorbed and displayed dose-proportional increases in exposure from 20 to 240 mg. Distribution was extensive and clearance low to moderate, resulting in a mean half-life of 48.3 h. Steady state was achieved by 15 days of dosing, consistent with single-dose PK, with a peak-to-trough ratio of 1.6. Two active metabolites circulated at similar to 10 % of osimertinib exposure. Ethnicity did not appear to affect exposure. Osimertinib PK profiles in healthy volunteers were similar to those in patients and were unaffected by formulation. Food caused a clinically insignificant increase in exposure. Osimertinib PK supports once-daily dosing; the same dose for Asian and non-Asian populations; a fixed-dosing approach; a minimal effect of food on exposure; and a switch to tablet formulation without alteration to dose or schedule. Osimertinib plasma concentrations are sustained throughout the dosing period, which is considered optimal for efficacy. | - |
dc.language | 영어 | - |
dc.publisher | Springer Verlag | - |
dc.title | Osimertinib Western and Asian clinical pharmacokinetics in patients and healthy volunteers: implications for formulation, dose, and dosing frequency in pivotal clinical studies | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 김동완 | - |
dc.identifier.doi | 10.1007/s00280-016-2992-z | - |
dc.citation.journaltitle | Cancer Chemotherapy and Pharmacology | - |
dc.identifier.wosid | 000374111500011 | - |
dc.identifier.scopusid | 2-s2.0-84959129318 | - |
dc.citation.endpage | 776 | - |
dc.citation.number | 4 | - |
dc.citation.startpage | 767 | - |
dc.citation.volume | 77 | - |
dc.identifier.sci | 000374111500011 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Kim, Dong-Wan | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | CELL LUNG-CANCER | - |
dc.subject.keywordPlus | T790M MUTATION | - |
dc.subject.keywordPlus | EGFR-TKI | - |
dc.subject.keywordPlus | ACQUIRED-RESISTANCE | - |
dc.subject.keywordPlus | NSCLC-PATIENTS | - |
dc.subject.keywordPlus | GEFITINIB | - |
dc.subject.keywordPlus | ADENOCARCINOMA | - |
dc.subject.keywordPlus | CHEMOTHERAPY | - |
dc.subject.keywordPlus | INHIBITORS | - |
dc.subject.keywordPlus | THERAPY | - |
dc.subject.keywordAuthor | Osimertinib | - |
dc.subject.keywordAuthor | Pharmacokinetics | - |
dc.subject.keywordAuthor | Bioavailability | - |
dc.subject.keywordAuthor | Food effect | - |
dc.subject.keywordAuthor | Multiple dose | - |
dc.subject.keywordAuthor | Single dose | - |
- Appears in Collections:
- Files in This Item:
- There are no files associated with this item.
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.