Chase dosing of lipid formulations to enhance oral bioavailability of nilotinib in rats

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dc.check.date2021-06-10
dc.check.infoAccess to this article is restricted until 12 months after publication by request of the publisher.en
dc.contributor.authorKoehl, Niklas J.
dc.contributor.authorHolm, René
dc.contributor.authorKuentz, Martin
dc.contributor.authorGriffin, Brendan T.
dc.contributor.funderHorizon 2020en
dc.date.accessioned2020-07-10T08:31:31Z
dc.date.available2020-07-10T08:31:31Z
dc.date.issued2020-06-10
dc.date.updated2020-07-10T08:03:07Z
dc.description.abstractPurpose: Lipid-based formulations (LBF) have shown oral bioavailability enhancement of lipophilic drugs, but not necessarily in the case of hydrophobic drugs. This study explored the potential of lipid vehicles to improve the bioavailability of the hydrophobic drug nilotinib comparing a chase dosing approach and lipid suspensions. Methods: Nilotinib in vivo bioavailability in rats was determined after administering an aqueous suspension chase dosed with blank olive oil, Captex 1000, Peceol or Capmul MCM, respectively. Absolute bioavailability was determined (relative to an intravenous formulation). Pharmacokinetic parameters were compared to lipid suspensions. Results: Compared to the lipid suspensions, the chase dosed lipids showed a 2- to 7-fold higher bioavailability. Both long chain chase dosed excipients also significantly increased the bioavailability up to 2-fold compared to the aqueous suspension. Deconvolution of the pharmacokinetic data indicated that chase dosing of nilotinib resulted in prolonged absorption compared to the aqueous suspension. Conclusion: Chase dosed LBF enhanced the in vivo bioavailability of nilotinib. Long chain lipids showed superior performance compared to medium chain lipids. Chase dosing appeared to prolong the absorption phase of the drug. Therefore, chase dosing of LBF is favourable compared to lipid suspensions for ‘brick dust’ molecules such as nilotinib.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid124en
dc.identifier.citationKoehl, N. J., Holm, R., Kuentz, M. and Griffin, B. T. (2020) 'Chase dosing of lipid formulations to enhance oral bioavailability of nilotinib in rats', Pharmaceutical Research, 37(7), 124 (11pp). doi: 10.1007/s11095-020-02841-9en
dc.identifier.doi10.1007/s11095-020-02841-9en
dc.identifier.eissn1573-904X
dc.identifier.endpage11en
dc.identifier.issn0724-8741
dc.identifier.issued7en
dc.identifier.journaltitlePharmaceutical Researchen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/10227
dc.identifier.volume37en
dc.language.isoenen
dc.publisherSpringer Nature Switzerland AGen
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::MSCA-ITN-ETN/674909/EU/Pharmaceutical Education And Research with Regulatory Links: Innovative drug development strategies and regulatory tools tailored to facilitate earlier access to medicines/PEARRLen
dc.rights© 2020, Springer Science + Business Media, LLC, part of Springer Nature. This is a post-peer-review, pre-copyedit version of an article published in Pharmaceutical Research. The final authenticated version is available online at: https://doi.org/10.1007/s11095-020-02841-9en
dc.subjectBrick dust moleculeen
dc.subjectChase dosingen
dc.subjectLipid based formulationen
dc.subjectLipid suspensionen
dc.subjectPoorly water-soluble drugsen
dc.titleChase dosing of lipid formulations to enhance oral bioavailability of nilotinib in ratsen
dc.typeArticle (peer-reviewed)en
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