Sökning: onr:"swepub:oai:DiVA.org:uu-330953" >
Biopharmaceutical i...
Biopharmaceutical investigations of doxorubicin formulations used in liver cancer treatment : Studies in healthy pigs and liver cancer patients, combined with pharmacokinetic and biopharmaceutical modelling
-
- Dubbelboer, Ilse R (författare)
- Uppsala universitet,Institutionen för farmaci
-
- Lennernäs, Hans, Professor (preses)
- Uppsala universitet,Institutionen för farmaci
-
- Sjögren, Erik, PhD (preses)
- Uppsala universitet,Institutionen för farmaci
-
visa fler...
-
- Derendorf, Hartmut, Professor (opponent)
- College of Pharmacy, University of Florida
-
visa färre...
-
(creator_code:org_t)
- ISBN 9789151301242
- Uppsala : Acta Universitatis Upsaliensis, 2017
- Engelska 70 s.
-
Serie: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, 1651-6192 ; 240
- Relaterad länk:
-
https://uu.diva-port... (primary) (Raw object)
-
visa fler...
-
https://uu.diva-port... (Preview)
-
https://urn.kb.se/re...
-
visa färre...
Abstract
Ämnesord
Stäng
- There are currently two types of drug formulation in clinical use in the locoregional treatment of intermediate hepatocellular carcinoma (HCC). In the emulsion LIPDOX, the cytostatic agent doxorubicin (DOX) is dissolved in the aqueous phase, which is emulsified with the oily contrast agent Lipiodol® (LIP). In the microparticular system DEBDOX, DOX is loaded into the drug-eluting entity DC Bead™.The overall aim of the thesis was to improve pharmaceutical understanding of the LIPDOX and DEBDOX formulations, in order to facilitate the future development of novel drug delivery systems. In vivo release of DOX from the formulations and the disposition of DOX and its active metabolite doxorubicinol (DOXol) were assessed in an advanced multisampling-site acute healthy pig model and in patients with HCC. The release of DOX and disposition of DOX and DOXol where further analysed using physiologically based pharmacokinetic (PBPK) and biopharmaceutical (PBBP) modelling. The combination of in vivo investigations and in silico modelling could provide unique insight into the mechanisms behind drug release and disposition.The in vivo release of DOX from LIPDOX is not extended and controlled, as it is from DEBDOX. With both formulations, DOX is released as a burst during the early phase of administration. The in vivo release of DOX from LIPDOX was faster than from DEBDOX in both pigs and patients. The release from DEBDOX was slow and possibly incomplete. The in vivo release of DOX from LIPDOX and DEBDOX could be described by using the PBBP model in combination with in vitro release profiles.The disposition of DOX and DOXol was modelled using a semi-PBPK model containing intracellular binding sites. The contrast agent Lipiodol® did not affect the hepatobiliary disposition of DOX in the pig model. The control substance used in this study, cyclosporine A, inhibited the biliary excretion of DOX and DOXol but did not alter metabolism in healthy pigs. The disposition of DOX is similar in healthy pigs and humans, which was shown by the ease of translation of the semi-PBPK pig model to the human PBBP model.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- drug delivery system
- in vivo release
- PBPK modelling
- hepatocellular carcinoma
- doxorubicin
- transarterial chemoembolization
- drug disposition
- Biofarmaci
- Biopharmaceutics
- Farmaceutisk vetenskap
- Pharmaceutical Science
Publikations- och innehållstyp
- vet (ämneskategori)
- dok (ämneskategori)
Hitta via bibliotek
Till lärosätets databas