Infusion pharmacokinetics of Lipocurc™ (liposomal curcumin) and its metabolite tetrahydrocurcumin in Beagle dogs.

Curcumin's instability and its metabolite, tetrahydrocurcumin (THC) pose a major issue for the establishment of dependable pharmacokinetics and excretion profiles. Additional pharmacokinetic variances are associated with durations of intravenous infusions. We found that stabilizing curcumin with phosphoric acid allows accurate quantitative determinations of curcuminoids in the plasma and bile, by preventing degradation during the analytical processes. Two male and two females dogs were infused with Lipocurc™ 10 mg/kg over two hours, and another four dogs (two males and two females) were infused with Lipocurc™ 10 mg/kg over eight hours. Plasma levels of curcumin and THC were determined during the infusions and at necropsy. THC levels were 6.3-9.6-fold higher than curcumin during both infusion rates, suggesting a combination of a high-rate of enzymatic curcumin metabolism and a comparatively slower rate of blood THC clearance. When levels of curcumin and THC were compared during infusion durations, the two-hour infusion levels were significantly higher than the eight-hour infusion. The plasma half-lives of both compounds following the two-hour infusion ranged from 0.4-0.7 hours, and was a consequence of both hepatic and renal clearance However, at higher plasma concentrations renal excretion predominated, particularly with THC. Enhanced clearance rates were noted during eight-hour infusions, which prevented achieving a steady state. These observations suggest that for leukemias and lymphomas, the two-hour infusion may be advantageous based upon higher concentration profiles, and unstimulated clearance rates, however data on curcumin penetration into circulating hematopoietic cancer cells and efficacy data are required in order to confirm these suggestions.