Clinical Evidence

Pharmacokinetics of liposomal curcumin (Lipocurc™) infusion: effect of co-medication in cancer patients and comparison with healthy individuals
Cancer Chemother Pharmacol.2019;83(2):265–275. doi:10.1007/s00280-018-3730-5
Curcumin is one of the plant-derived bioactives with a multitude of pharmacological benefits. However, its usefulness is limited by the reduced solubility and absorption leading to poor bioavailability. Reports state that even intravenous injection of curcumin will not improve the bioavailability because of its rapid metabolism into tetrahydrocurcumin (THC) and hexahydrocurcumin by reductases. It has been shown that certain drugs, affecting the liver enzymes involved in xenobiotics, affect the bioavailability of curcumin by reducing its metabolism by the liver enzymes. Hence co-administration of curcumin along with other drugs is the current strategy to improve the bioavailability of the curcumin.
Objective:

To study the effect of co-medication (Curcumin and THC with other medications) on the plasma levels of curcumin and tetrahydrocurcumin (THC) in cancer patients and to compare the pharmacokinetics of curcumin and THC between cancer patients and healthy individuals following intravenous infusion of Lipocurc™.

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. Another In vitro experiment using hepatocyte and red blood cells was 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:
  • Out 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 the 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 the 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.