Abstract 756: Pharmacokinetics of curcumin and curcumin O-glucuronide in healthy volunteers characterized by liquid chromatography-tandem mass spectrometry

Abstract

Abstract Purpose: To develop and validate a liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for simultaneous quantification of curcumin and curcumin O-glucuronide (COG) in human plasma, and to characterize the pharmacokinetics (PK) of curcumin and COG in healthy volunteers after separate oral administrations of Curcumin C3 Complex (CC3C) and nano-emulsion Curcumin (NEC) using this method. Methods: The study was conducted at The Ohio State University (OSU) with the approval of the OSU Institutional Review Board. CC3C and NEC were administered orally to four healthy volunteers and plasma levels of curcumin and COG were determined by a validated LC-MS/MS method. The pharmacokinetic parameters were calculated using WinNonlin computer software. Clinical safety assessment included vital signs and biochemical measurement on the day of each PK study and three weeks following each PK study to monitor potential toxicity. A mixed effect model was used for comparing the concentration of curcumin or COG at each time point after the oral consumption of CC3C or NEC across each donor using SAS 9.2 software. Results: An LC-MS/MS method for simultaneous quantification of curcumin and COG in human plasma with the lower limit of quantification of 2 ng/mL was established. The within-day and between-day validation parameters were consistent with the Food and Drug Administration's (FDA) criteria for Good Laboratory Practice analytical methods. A cross-over pharmacokinetic study in the four healthy volunteers revealed that 2g NEC delivered much higher plasma concentrations of free curcumin (1.5-8.0 ng/mL vs. non-detectable, p<0.001, paired t-test) and COG (550-3300 ng/mL vs. 3.0-167 ng/mL, p<0.05, paired t-test) when compared to 4g of CC3C. The total drug exposure of curcumin and COG from NEC in human volunteers is 26 to 350-fold higher than that of CC3C. No adverse events were noted following administrations of CC3C and NEC. No abnormalities were noted on the hematologic, clinical chemistry, and metabolic profiles at prescreening, and at 3 weeks following CC3C and NEC administration. Conclusion: NEC represents a novel formulation of curcumin with enhanced oral absorption of curcumin and is worthy of evaluation for future clinical applications. Supported by NIH-NCI-R21 CA135478 [ZL], UL1RR025755 [NCRR] and the BioMedical Mass Spectrometry Laboratory [KC & ZL]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 756. doi:1538-7445.AM2012-756