Porcine and Human In Vivo Simulations for Doxorubicin-Containing Formulations Used in Locoregional Hepatocellular Carcinoma Treatment

The AAPS Journal
Ilse R DubbelboerHans Lennernäs

Abstract

It is important to be able to simulate and predict formulation effects on the pharmacokinetics of a drug in order to optimize effectivity in clinical practice and drug development. Two formulations containing doxorubicin are used in the treatment of hepatocellular carcinoma (HCC): a Lipiodol-based emulsion (LIPDOX) and a loadable microbead system (DEBDOX). Although equally effective, the formulations are vastly different, and little is known about the parameters affecting doxorubicin release in vivo. However, mathematical modeling can be used to predict doxorubicin release properties from these formulations and its in vivo pharmacokinetic (PK) profiles. A porcine semi-physiologically based pharmacokinetic (PBPK) model was scaled to a human physiologically based biopharmaceutical (PBBP) model that was altered to include HCC. DOX in vitro and in vivo release data from LIPDOX or DEBDOX were collected from the literature and combined with these in silico models. The simulated pharmacokinetic profiles were then compared with observed porcine and human HCC patient data. DOX pharmacokinetic profiles of LIPDOX-treated HCC patients were best predicted from release data sets acquired by in vitro methods that did not use a diffusion barri...Continue Reading

References

Jan 1, 1989·Cancer Chemotherapy and Pharmacology·Y KatagiriT Kawai
Nov 1, 1994·Journal of Vascular and Interventional Radiology : JVIR·Z Kan, S Wallace
Aug 1, 1998·Journal of Controlled Release : Official Journal of the Controlled Release Society·S W YiS Y Jeong
Jan 5, 2002·Journal of Controlled Release : Official Journal of the Controlled Release Society·Buddy D Ratner
Mar 7, 2006·Journal of Vascular and Interventional Radiology : JVIR·Andrew L LewisPeter W Stratford
Jul 27, 2007·Journal of Materials Science. Materials in Medicine·M Victoria GonzalezAndrew L Lewis
Mar 24, 2009·AJR. American Journal of Roentgenology·Jin IwazawaKenji Nakamura
Feb 4, 2010·Journal of Vascular and Interventional Radiology : JVIR·Julien NamurAlexandre Laurent
Feb 9, 2012·The Journal of Pharmacy and Pharmacology·Helen GrahamLeon Aarons
Mar 20, 2012·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·UNKNOWN European Association for Study of Liver, UNKNOWN European Organisation for Research and Treatment of Cancer
Aug 28, 2013·Diagnostic and Interventional Imaging·J CazejustY Menu
Sep 26, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Edmund S KostewiczJennifer Dressman
Feb 25, 2014·Molecular Pharmaceutics·Ilse R DubbelboerHans Lennernäs
Sep 16, 2014·Expert Opinion on Drug Metabolism & Toxicology·Martha GonzalezItalo Poggesi
Sep 16, 2014·International Journal of Cancer. Journal International Du Cancer·Jacques FerlayFreddie Bray
Apr 7, 2015·International Journal of Pharmaceutics·E AhnfeltH Lennernäs
Oct 1, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jie Shen, Diane J Burgess
Feb 7, 2016·Journal of Vascular and Interventional Radiology : JVIR·Ron C GabaUNKNOWN Society of Interventional Radiology Technology Assessment Committee
Sep 25, 2016·Journal of Pharmaceutical Sciences·Emelie AhnfeltHans Lennernäs
Nov 25, 2016·The Journal of Pharmacy and Pharmacology·Elsa LilienbergHans Lennernäs
May 24, 2017·Journal of Vascular and Interventional Radiology : JVIR·Hadrien D'incaGérard Thiéfin

❮ Previous
Next ❯

Citations

Feb 14, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Xiaohong LiGuang Yang

❮ Previous
Next ❯

Methods Mentioned

BETA
in silico methodology
profiler

Software Mentioned

WinNonLin
AAFE
PlotDigitizer
Berkeley Madonna

Related Concepts

Related Feeds

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.