Gordon T Bolger1, Albert Licollari2, Amin Tan2, Richard Greil3,4,5, Brigitta Vcelar6, Sigrun Greil-Ressler3,4, Lukas Weiss3,4, Charlotte Schönlieb3,4, Teresa Magnes3,4, Bianca Radl3,4, Muhammed Majeed7, Peter P Sordillo8. 1. Nucro-Technics, 2000 Ellesmere Road, Unit 16, Scarborough, ON, M1H 2W4, Canada. bolger@nucro-technics.com. 2. Nucro-Technics, 2000 Ellesmere Road, Unit 16, Scarborough, ON, M1H 2W4, Canada. 3. III rd Medical Department, Paracelsus Medical University Salzburg, Salzburg, Austria. 4. Salzburg Cancer Research Institute-Center for Clinical Cancer and Immunology Trials (SCRI-CCCIT), Salzburg, Austria. 5. Cancer Cluster Salzburg, Salzburg, Austria. 6. Polymun Scientific Immunbiologische Forschung GmbH, Klosterneuburg, Austria. 7. Sabinsa Corporation, East Windsor, NJ, USA. 8. SignPath Pharma, Inc, 51 East 82 Street, #1A, New York, NY, 10028, USA. psordillo@signpathpharma.com.
Abstract
PURPOSE: Investigation of the impact of co-medication on the plasma levels of curcumin and tetrahydrocurcumin (THC) in cancer patients and a comparison of the pharmacokinetics of curcumin and plasma levels of THC between cancer patients and healthy individuals following intravenous infusion of Lipocurc™ (liposomal curcumin). METHODS: Correlation analysis was used to determine the impact of co-medication on infusion rate normalized plasma levels of curcumin and THC in cancer patients and to compare the plasma levels of curcumin and THC at different infusion rates between cancer patients and healthy individuals. In vitro hepatocyte and red blood cell distribution experiments were conducted with Lipocurc™ to support clinical findings. Plasma concentration time data were analyzed by the non-compartmental method to determine and compare the pharmacokinetic parameters of curcumin in cancer patients and healthy individuals. RESULTS: Of 44 co-medications studied, three medications targeting the renin-angiotensin system, Lisinopril, Ramipril, and Valsartan elevated plasma levels of curcumin and THC in three cancer patients infused with Lipocurc™. Cell distribution experiments indicated that the disposition of curcumin in red blood cells may be a target for elevation of the plasma levels of curcumin. Plasma levels of curcumin in cancer patients increased to a greater extent with increased infusion rate compared to healthy individuals. Upon termination of infusion, the elimination phase for curcumin was shorter with a shorter terminal half-life and smaller volume of distribution for curcumin in cancer patients compared to healthy individuals. CONCLUSION: Either co-medications or health status, or both, can impact the pharmacokinetics of curcumin infusion (as Lipocurc™) in cancer patients.
PURPOSE: Investigation of the impact of co-medication on the plasma levels of curcumin and tetrahydrocurcumin (THC) in cancerpatients and a comparison of the pharmacokinetics of curcumin and plasma levels of THC between cancerpatients and healthy individuals following intravenous infusion of Lipocurc™ (liposomal curcumin). METHODS: Correlation analysis was used to determine the impact of co-medication on infusion rate normalized plasma levels of curcumin and THC in cancerpatients and to compare the plasma levels of curcumin and THC at different infusion rates between cancerpatients and healthy individuals. In vitro hepatocyte and red blood cell distribution experiments were conducted with Lipocurc™ to support clinical findings. Plasma concentration time data were analyzed by the non-compartmental method to determine and compare the pharmacokinetic parameters of curcumin in cancerpatients and healthy individuals. RESULTS: Of 44 co-medications studied, three medications targeting the renin-angiotensin system, Lisinopril, Ramipril, and Valsartan elevated plasma levels of curcumin and THC in three cancerpatients infused with Lipocurc™. Cell distribution experiments indicated that the disposition of curcumin in red blood cells may be a target for elevation of the plasma levels of curcumin. Plasma levels of curcumin in cancerpatients increased to a greater extent with increased infusion rate compared to healthy individuals. Upon termination of infusion, the elimination phase for curcumin was shorter with a shorter terminal half-life and smaller volume of distribution for curcumin in cancerpatients compared to healthy individuals. CONCLUSION: Either co-medications or health status, or both, can impact the pharmacokinetics of curcumin infusion (as Lipocurc™) in cancerpatients.
Entities:
Keywords:
Cancer patients; Co-medications; Curcumin; Pharmacokinetics; Tetrahydrocurcumin