Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine.
OBJECTIVE
Curcumin, a major constituent of the spice turmeric, suppresses expression of the enzyme cyclooxygenase 2 (Cox-2) and has cancer chemopreventive properties in rodents. It possesses poor systemic availability. We explored whether formulation with phosphatidylcholine increases the oral bioavailability or affects the metabolite profile of curcumin.


METHODS
Male Wistar rats received 340 mg/kg of either unformulated curcumin or curcumin formulated with phosphatidylcholine (Meriva) by oral gavage. Rats were killed at 15, 30, 60 and 120 min post administration. Plasma, intestinal mucosa and liver were analysed for the presence of curcumin and metabolites using HPLC with UV detection. Identity of curcumin and metabolites was verified by negative ion electrospray liquid chromatography/tandem mass spectrometry.


RESULTS
Curcumin, the accompanying curcuminoids desmethoxycurcumin and bisdesmethoxycurcumin, and the metabolites tetrahydrocurcumin, hexahydrocurcumin, curcumin glucuronide and curcumin sulfate were identified in plasma, intestinal mucosa and liver of rats which had received Meriva. Peak plasma levels and area under the plasma concentration time curve (AUC) values for parent curcumin after administration of Meriva were fivefold higher than the equivalent values seen after unformulated curcumin. Similarly, liver levels of curcumin were higher after administration of Meriva as compared to unformulated curcumin. In contrast, curcumin concentrations in the gastrointestinal mucosa after ingestion of Meriva were somewhat lower than those observed after administration of unformulated curcumin. Similar observations were made for curcumin metabolites as for parent compound.


CONCLUSIONS
The results suggest that curcumin formulated with phosphatidylcholine furnishes higher systemic levels of parent agent than unformulated curcumin.
Marczylo
Timothy H
TH
Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, LE2 7LX, UK. thm3@le.ac.uk
Verschoyle
Richard D
RD
Cooke
Darren N
DN
Morazzoni
Paolo
P
Steward
William P
WP
Gescher
Andreas J
AJ
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008081:Liposomes; D008297:Male; D010713:Phosphatidylcholines / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
D000970:Antineoplastic Agents; D008081:Liposomes; D010713:Phosphatidylcholines; D003474:Curcumin