Title : Comparative human PK-study under fed conditions with three marketed oral curcuminoid products and first-time a pure intravenous curcumin (Diferuloylmethan)
Abstract:
Objective and Design: The task of this study was to measure the plasma concentration and kinetics of three different marketed oral Curcuminoid-products and the one available synthetic Diferuloylmethan i.v. preparation under fed conditions in an open-label, balanced, randomized, single-dose, four-treatment, four-period, four sequence, four-way crossover, single-blind study in healthy, adult, human subjects, to compare the relative bioavailability and pharmacokinetic of free curcuminoids/curcumin of these products under realistic treatment conditions in humans. International Study Number SLS-CT-0002-19-CURC. Methods and Realization: Six healthy Indian men and 6 healthy Indian woman, 18 to 45 years of age with a body-massindex of 18.5 – 25.0 kg/m2 were supplied (after a washout period of one week) 30 minutes after a standard meal with a single dose of CUREminACTIF® one capsule (Cureit® 125 mg of Curcuminoids + 125 mg Tumeric matrix, 90 mg of Curcumin), or MERIVA® Thorne capsule (500 mg Curcumin Phytosome/phospholipid complex, 80 mg of Curcumin), or Curcumin-Loges® one capsule (NOVAsol®, 50.4 curcuma extract in 450 mg Tween-80®, 35,5 mg Curcumin), or an intravenous infusion of 150 mg diferuloylmethan in 250 ml 0.9% NaCl over a time period of 2 hours (Burg Apotheke® 150 mg diferuloylmethan). Blood samples were taken before and up to 48 hours after compound application at 21 time points. The free curcumin concentration was determined in plasma samples by UPLC/ESI-Q-TOF-MS spectrometry. Results: 11 from 12 individuals completed the study, one female had to be excluded do to noncompliance to the protocol. No adverse effects and no biochemical abnormalities have been reported. The AUC0-24h (ng/mlxh) normalized to 1 mg Curcumin substituted, calculated as mean AUC0-24h from individual subjects (Mean + SD) was 14.34+6.86 (CUREminActif®), 7.02+3.74 (MERIVA®), 15.88+8.61 (Curcumin-Loges®) and 15.13+14.76 (i.v. Burg Apotheke®). The bioavailability of CUREmin Actif® (Cureit®) and MERIVA® was 3-fold increased compared to application under fasting conditions. AUC0-24h Cureit® 4.58 ng/mlxh, MERIVA® 2.33 ng/mlxh [Gopi S. et al. 2017 Phytother Res 31(12):1883- 1891] measurements performed under same analytical conditions. The Tmax of the orally applied Curcuminoid preparations was at 2 hours, that of the intravenous Curcumin at 0.75 hours. All, the oral and the intravenously applied curcumin preparations showed a high inter-individual coefficient of variation. Summary: The claimed vast superiority of Curcumin Loges® (NOVAsol®) above other oral Curcuminoid preparations could not be verified [Schiborr C et al. 2014 Mol Nutr Food Res 58:516-527] Unexpectedly the intravenous applied pure Curcumin did not show a superior bioavailability to CUREminACTIF®/Cureit® and Curcumin-Loges® in terms of the free curcumin content in the blood plasma.
