Tissue distribution of (Lipocurc™) liposomal curcumin and tetrahydrocurcumin following two- and eight-hour infusions in Beagle dogs.
This study interrogated whether different durations of intravenous infusions of lipocurc™ would alter curcumin metabolism, tissue distribution and whether treating necropsied tissues of Beagle dogs with phosphoric acid prior to measuring curcumin and its metabolite, tetrahydrocurcumin (THC), would stabilize the compounds allowing for accurate analytic measurements. Two cohorts comprising two male and two female dogs were infused each intravenously with 10 mg/kg lipocurc™, either over two hours or over eight hours. Tissue data from each cohort was averaged from four dogs. Curcumin and THC distributed among all 13 tissues were examined at necropsy. The highest curcumin level was observed in the lungs followed by the liver. Tissue levels of curcumin in the lung, spleen and liver increased substantially following the eight-hour infusion compared to the two-hour infusion. The pancreas, kidney and urinary bladder also contained relatively high curcumin levels. Tissue partition coefficients for curcumin and THC were also higher for the eight-hour infusion than the two-hour infusion. The tissue THC/curcumin ratio varied in a tissue-specific manner and was lower for the eight-hour compared to the two-hour infusion. In conclusion, this raised the possibility that prolonged infusion of curcumin may facilitate distribution into tissues via a transporter-dependent mechanism and elevated tissue concentrations of curcumin may inhibit or saturate a putative reductase enzyme converting curcumin to THC. The addition of phosphoric acid stabilized the levels of curcumin and THC in some but not all the examined tissues, raising issues of tissue-specific curcumin and THC stability.
SignPath Pharma, Inc 1375 California Road, Quakertown, PA 18951, USA.
Dharmendr
D
Matabudul
Kresimir
K
Pucaj
Gordon
G
Bolger
Brigitta
B
Vcelar
Muhammed
M
Majeed
Lawrence
L
Helson
D000818:Animals; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D004285:Dogs; D005260:Female; D007262:Infusions, Intravenous; D008081:Liposomes; D008297:Male; D010756:Phosphoric Acids / Q000032:analysis; D014018:Tissue Distribution
D008081:Liposomes; D010756:Phosphoric Acids; C096277:tetrahydrocurcumin; C030242:phosphoric acid; D003474:Curcumin