Physiologically-Based Pharmacokinetic Predictions of the Effect of Curcumin on Metabolism of Imatinib and Bosutinib: In Vitro and In Vivo Disconnect

Pharmaceutical Research
Jeffry AdiwidjajaAndrew J McLachlan

Abstract

This study aimed to investigate the potential pharmacokinetic interactions between curcumin, imatinib and bosutinib, combining In Vitro and in silico methods. In Vitro metabolism of imatinib and bosutinib were investigated in pooled human liver microsomes and recombinant CYP3A4 enzyme in the presence and absence of curcumin and curcumin glucuronide using an LC-MS/MS assay for N-desmethyl metabolites. A physiologically-based pharmacokinetic (PBPK) model for curcumin formulated as solid lipid nanoparticles (SLN) was constructed using In Vitro glucuronidation kinetics and published clinical pharmacokinetic data. The potential effects of curcumin coadministration on systemic exposures of imatinib and bosutinib were predicted in silico using PBPK simulations. Curcumin demonstrated potent reversible inhibition of cytochrome P450 (CYP)3A4-mediated N-demethylation of imatinib and bosutinib and CYP2C8-mediated metabolism of imatinib with inhibitory constants (ki,u) of ≤1.5 μmol. L-1. A confirmatory In Vitro study with paclitaxel, the 6α-hydroxylation of which is exclusively mediated by CYP2C8, was consistent with a potent inhibition of this enzyme by curcumin. Curcumin glucuronide also inhibited both CYP enzymes In Vitro, albeit to a le...Continue Reading

References

Dec 1, 1978·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·G M HolderA J Ryan
Jan 1, 1981·Pharmacology & Therapeutics·J B Houston
Aug 9, 2002·Biochemical Pharmacology·Songyot AnuchapreedaPorn-ngarm Limtrakul
Oct 8, 2003·Current Drug Metabolism·Karthik VenkatakrishnanDavid J Greenblatt
Nov 30, 2005·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Trevor N JohnsonAmin Rostami-Hodjegan
Mar 21, 2007·Pharmaceutical Research·Trudy Rodgers, Malcolm Rowland
Jul 14, 2007·Molecular Nutrition & Food Research·Simone I HoehleManfred Metzler
Jun 19, 2008·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Shaiju K VareedDean E Brenner
Sep 9, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Z E BarterA Rostami-Hodjegan
Oct 29, 2008·Evidence-based Complementary and Alternative Medicine : ECAM·Jae KennedyChung-Hsuen Wu
Apr 22, 2009·The AAPS Journal·Masoud JameiGeoffrey Tucker
Jan 23, 2010·Journal of Agricultural and Food Chemistry·Vikram S GotaManish G Agarwal
Dec 15, 2010·British Journal of Clinical Pharmacology·Eleanor J GuestAleksandra Galetin
Jan 18, 2011·British Journal of Clinical Pharmacology·Yong LiuMark J Ratain
May 17, 2011·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Paresh DadhaniyaMadhu G Soni
Jun 26, 2012·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·X HeD-S Ouyang
Sep 25, 2012·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Cécile ArellanoEtienne Chatelut
Oct 3, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Anne M FilppulaJanne T Backman
Mar 12, 2013·Expert Review of Clinical Pharmacology·Karen Rowland YeoAmin Rostami-Hodjegan
Mar 29, 2014·CPT: Pharmacometrics & Systems Pharmacology·S J BrantleyM F Paine
May 6, 2014·Profiles of Drug Substances, Excipients, and Related Methodology·Maria L A D Lestari, Gunawan Indrayanto
Jul 11, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Brandon T GuffordMary F Paine
Oct 4, 2014·Journal of Psychopharmacology·Katherine Hm CoxAndrew B Scholey
Dec 17, 2014·International Journal of Clinical Pharmacology and Therapeutics·Angela StorkaMichael Wolzt
Jan 1, 2013·In Silico Pharmacology·Masoud JameiAmin Rostami-Hodjegan
Jun 4, 2015·Expert Review of Neurotherapeutics·Shuxin HuSally A Frautschy
Oct 17, 2015·Nature Reviews. Drug Discovery·Natalie L TrevaskisChristopher J H Porter
Jan 19, 2016·Regulatory Toxicology and Pharmacology : RTP·Amy L RoeJames C Griffiths
Apr 9, 2016·Journal of Basic and Clinical Pharmacy·Anroop B Nair, Shery Jacob
Aug 4, 2016·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yannick ParmentierBernard Walther
Jan 1, 2017·Biopharmaceutics & Drug Disposition·Oliver J D HatleyAmin Rostami-Hodjegan

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Citations

Nov 12, 2021·Recent Patents on Anti-cancer Drug Discovery·Lu ChenWanyi Chen

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Methods Mentioned

BETA
pharmacotherapy

Clinical Trials Mentioned

NCT01811381

Software Mentioned

GraphPad
GraphPad Prism
Simcyp Simulator

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