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

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dc.contributor.author Koehl, Niklas J.
dc.contributor.author Holm, René
dc.contributor.author Kuentz, Martin
dc.contributor.author Griffin, Brendan T.
dc.date.accessioned 2020-07-10T08:31:31Z
dc.date.available 2020-07-10T08:31:31Z
dc.date.issued 2020-06-10
dc.identifier.citation Koehl, 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/s11095-020-02841-9 en
dc.identifier.volume 37 en
dc.identifier.issued 7 en
dc.identifier.startpage 1 en
dc.identifier.endpage 11 en
dc.identifier.issn 0724-8741
dc.identifier.uri http://hdl.handle.net/10468/10227
dc.identifier.doi 10.1007/s11095-020-02841-9 en
dc.description.abstract Purpose: 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.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Springer Nature Switzerland AG en
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/s11095-020-02841-9 en
dc.subject Brick dust molecule en
dc.subject Chase dosing en
dc.subject Lipid based formulation en
dc.subject Lipid suspension en
dc.subject Poorly water-soluble drugs en
dc.title Chase dosing of lipid formulations to enhance oral bioavailability of nilotinib in rats en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Niklas Koehl, Pharmacology & Therapeutics, University College Cork, Cork, Ireland. +353-21-490-3000 Email: niklas.koehl@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted until 12 months after publication by request of the publisher. en
dc.check.date 2021-06-10
dc.date.updated 2020-07-10T08:03:07Z
dc.description.version Accepted Version en
dc.internal.rssid 519780562
dc.contributor.funder Horizon 2020 en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Pharmaceutical Research en
dc.internal.copyrightchecked Yes
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress niklas.koehl@ucc.ie en
dc.identifier.articleid 124 en
dc.relation.project info: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/PEARRL en
dc.identifier.eissn 1573-904X


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