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Pharmacokinetic characteristics of vactosertib, a new activin receptor-like kinase 5 inhibitor, in patients with advanced solid tumors in a first-in-human phase 1 study
DC Field | Value | Language |
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dc.contributor.author | Jung, Su Young | - |
dc.contributor.author | Hwang, Sunjin | - |
dc.contributor.author | Clarke, Jeffery M. | - |
dc.contributor.author | Bauer, Todd M. | - |
dc.contributor.author | Keedy, Vicki L. | - |
dc.contributor.author | Lee, Hukeun | - |
dc.contributor.author | Park, Neunggyu | - |
dc.contributor.author | Kim, Seong-Jin | - |
dc.contributor.author | Lee, Jangik I. | - |
dc.date.accessioned | 2023-04-19T00:33:06Z | - |
dc.date.available | 2023-04-19T00:33:06Z | - |
dc.date.created | 2020-04-01 | - |
dc.date.created | 2020-04-01 | - |
dc.date.issued | 2020-06 | - |
dc.identifier.citation | Investigational New Drugs, Vol.38 No.3, pp.812-820 | - |
dc.identifier.issn | 0167-6997 | - |
dc.identifier.uri | https://hdl.handle.net/10371/190312 | - |
dc.description.abstract | Purposes Vactosertib is a new investigational inhibitor of activin receptor-like kinase 5. The objective of this study was to characterize vactosertib pharmacokinetics that are to be applied for subsequent clinical studies. Methods Vactosertib plasma concentration-time data were obtained from a multicenter, dose-escalation, first-in-human phase 1 study conducted in patients with advanced solid tumors. Each patient orally received a fixed dose of vactosertib with the range of 30 mg to 340 mg once daily under fasted condition. Pharmacokinetic analysis was performed using a non-compartmental method. Results Pharmacokinetic data were evaluable in 29 patients. Vactosertib was rapidly absorbed after the first dose with a median time to maximum concentration (t(max)) of 1.2 h (interquartile range, 0.8-1.8 h) and quickly eliminated with a median terminal half-life (t(1/2)) of 3.2 h (2.2-4.2 h) over the dose range studied. Such trend was also observed after repeated doses for five days (median t(max), 1.5 h; median t(1/2), 3.0 h). The area under the concentration-time curve within a dosing interval increased in proportion to dose. The median values of apparent clearance and volume of distribution were 29 L/h (21-44 L/h) and 133 L (77-222 L), respectively. The median accumulation ratio after repeated once-daily doses for five days was 0.87 (0.69-1.07). Conclusions Vactosertib pharmacokinetics were dose-proportional within tested dose range with negligible accumulation when administered once daily for five days. Considering the short half-life, it seems necessary to administer vactosertib twice- or thrice-daily to maintain its concentrations above minimum effective level over a dosing interval. | - |
dc.language | 영어 | - |
dc.publisher | Kluwer Academic Publishers | - |
dc.title | Pharmacokinetic characteristics of vactosertib, a new activin receptor-like kinase 5 inhibitor, in patients with advanced solid tumors in a first-in-human phase 1 study | - |
dc.type | Article | - |
dc.identifier.doi | 10.1007/s10637-019-00835-y | - |
dc.citation.journaltitle | Investigational New Drugs | - |
dc.identifier.wosid | 000531213000023 | - |
dc.identifier.scopusid | 2-s2.0-85068927663 | - |
dc.citation.endpage | 820 | - |
dc.citation.number | 3 | - |
dc.citation.startpage | 812 | - |
dc.citation.volume | 38 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Lee, Jangik I. | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | TGF-BETA | - |
dc.subject.keywordPlus | TRIAL | - |
dc.subject.keywordAuthor | Vactosertib | - |
dc.subject.keywordAuthor | ALK5 inhibitor | - |
dc.subject.keywordAuthor | Pharmacokinetics | - |
dc.subject.keywordAuthor | First-in-human study | - |
dc.subject.keywordAuthor | Solid tumors | - |
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