Preclinical Evidence

Pharmacokinetics of liposomal curcumin (Lipocurc™) infusion: effect of co-medication in cancer patients and comparison with healthy individuals
Cancer Chemother. Pharmacol.2019 Feb;83(2):265-275
“Curcumin is being explored by numerous studies for its anticancer properties. However, its utility is limited by poor oral bioavailability. It has a shorter half-life and rapid systemic elimination following parenteral administration due to metabolism. Nano-formulations of curcumin developed to improve its bioavailability were also found efficacious to suppress the pancreatic tumour growth, lymphocyte count as well as to increase the scavenging cells. With the availability and efficacy of nano-formulations of curcumin, it became imperative to study about the influence of co-medication on the pharmacokinetic profile of liposomal curcumin formulation (containing 6.0 mg/mL curcumin) in cancer patients.”
Objective:

To investigate the impact of co-medication on the plasma levels of curcumin and Tetrahydrocurcumin (THC) in cancer patients compared to healthy individuals following intravenous infusion of liposomal curcumin.

Methodology:

Freshly isolated red blood cells (RBCs), cryopreserved hepatocytes obtained from male Beagle dog and male human donors were used in this study for in vitro distribution experiments with liposomal curcumin. The pharmacokinetic profiles of curcumin and THC in healthy individuals (phase I) and cancer patients (phase Ib) were also compared by analyzing the plasma profiles.

Results and Discussion:
  • Among the medications studied, the medication affecting
    rennin—angiotensin system were found to elevate the normalized plasma levels of curcumin and THC in patients with cancer, while the rest of the medications did not show major alterations
  • The presence of ACE inhibitor during the incubation has decreased the levels of curcumin in human RBCs, hepatocytes and RBC medium, while it was increased in the dog RBCs (p<0.01), RBC medium (p<0.01) and hepatocytes
  • The levels of THC were decreased in human RBCs but slightly increased in human hepatocytes and RBC medium. The levels of THC were contrastingly changed in dog cells and dog cell medium, i.e., they have increased in dog RBCs as well as hepatocytes (p<0.01), but decreased in RBC medium (p<0.01)
  • The plasma levels of curcumin in cancer patients increased with increased infusion rates compared to healthy individuals
  • The elimination of curcumin was faster with a shorter terminal half-life, also showed a smaller volume of distribution in patients with cancer than healthy individuals
  • Despite the lower infusion rates of curcumin in cancer patients, the plasma concentrations of curcumin during infusion were in a similar range as those of healthy individuals
Conclusion

It was found that the co-medications and health status, either or both, impact the pharmacokinetics of curcumin in the cancer patients.