Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects
ABSTRACT Curcumin is a polyphenol, found in the spice turmeric, that has promising anticancer properties, but previous studies suggest that absorption of curcumin may be limited.
This study examined the pharmacokinetics of a curcumin preparation in healthy human volunteers 0.25 to 72 h after a single oral dose. Curcumin was administered at doses of 10 g (n = 6) and 12 g (n = 6). Subjects were randomly allocated to dose level for a total of six subjects at each dose level. Serum samples were assayed for free curcumin, for its glucuronide, and for its sulfate conjugate. The data were fit to a one-compartment absorption and elimination model.
Using a high-performance liquid chromatography assay with a limit of detection of 50 ng/mL, only one subject had detectable free curcumin at any of the 14 time points assayed, but curcumin glucuronides and sulfates were detected in all subjects. Based on the pharmacokinetic model, the area under the curve for the 10 and 12 g doses was estimated (mean +/- SE) to be 35.33 +/- 3.78 and 26.57 +/- 2.97 mug/mL x h, respectively, whereas C(max) was 2.30 +/- 0.26 and 1.73 +/- 0.19 mug/mL. The T(max) and t(1/2) were estimated to be 3.29 +/- 0.43 and 6.77 +/- 0.83 h. The ratio of glucuronide to sulfate was 1.92:1. The curcumin conjugates were present as either glucuronide or sulfate, not mixed conjugates.
Curcumin is absorbed after oral dosing in humans and can be detected as glucuronide and sulfate conjugates in plasma.
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ABSTRACT: The aim of this study was to examine the efficacy of self-nano phospholipid dispersions (SNPDs) based on Phosal® to improve the oral bioavailability of curcumin (CUR). SNPDs were prepared with Phosal ® 53 and Miglyol 812 at different surfactant ratio. Formulations were evaluated for particle size, polydispersity index, zeta potential, and robustness toward dilution, TEM as well as in vitro drug release. The in vivo oral absorption of selected formulations in comparison to drug suspension was evaluated in rats. Moreover, formulations were assessed for in vitro characteristic changes before and after storage. The SNPDs were miscible with water in any ratio and did not show any phase separation or drug precipitation. All the formulas were monodisperse with nano range size from 158 ± 2.6nm to 610 ± 6.24nm. They passed the pharmacopeial tolerance for CUR dissolution. No change in dissolution profile and physicochemical characteristics was detected after storage. CUR- SNPDs are found to be more bioavailable compared with suspension during an in vivo study in rats and in vitro release studies failed to imitate the in vivo conditions. These formulations might be new alternative carriers that enhance the oral bioavailability of poorly water-soluble molecules, such as CUR. Copyright © 2015. Published by Elsevier B.V.International Journal of Pharmaceutics 04/2015; 489(1-2). DOI:10.1016/j.ijpharm.2015.04.067 · 3.79 Impact Factor
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ABSTRACT: BACKGROUND: Few natural products have demonstrated the range of protective and therapeutic promise as have turmeric and its principal bioactive components: curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Success in translating this potential into tangible benefits has been limited by inherently poor intestinal absorption, rapid metabolism, and limited systemic bioavailability. Seeking to overcome these limitations, food ingredient formulators have begun to employ a variety of approaches to enhance absorption and bioactivity. Many of these strategies improve upon the age-old practice of consuming turmeric in fat-based sauces, such as in a fat-rich yellow curry. However, there exists uncertainty as to how the various commercially available offerings compare to each other in terms of either uptake or efficacy, and this uncertainty leaves physicians and nutritionists with a dearth of data for making recommendations to interested patients and consumers. Further complicating the issue are recent data suggesting that formulation strategies may not equally enhance the absorption of individual curcuminoids, a significant issue in that these curcuminoids exhibit somewhat different physiologic properties. Available at: http://www.tandfonline.com/doi/full/10.1080/07315724.2014.950392Journal of the American College of Nutrition 04/2015; DOI:10.1080/07315724.2014.950392 · 1.68 Impact Factor
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ABSTRACT: Introduction: Experimental studies have shown that liposomal curcumin can exert a reduction in tumor growth in pancreatic and colorectal cancer. In this phase I clinical trial we investigated the pharmacokinetics, safety, and tolerability of intravenously administered liposomal curcumin in healthy subjects. Material and methods: 50 male and female participants were included in this randomized, placebo-controlled double-blind phase I dose escalation study. Subjects received a single dose of liposomal curcumin (10 - 400 mg/m2; n = 2 - 6 per group) or placebo over 2 hours intravenously. Results: Dose-dependent increases in the plasma concentrations of curcumin and its metabolite tetrahydrocurcumin (THC) were detected. After the end of drug infusion, curcumin and THC plasma concentrations decreased within 6 - 60 minutes below the limit of quantification. Mean urinary excretion was ~ 0.1% of total systemic clearance. Liposomal curcumin was tolerated well, but a transient red blood cell echinocyte formation with concomitant increase in mean cellular volume was observed at dosages â¥ 120 mg/m2. Conclusion: Short-term intravenous dosing of liposomal curcumin appears to be safe up to a dose of 120 mg/m2. Changes in red blood cell morphology may represent a dose limiting sign of toxicity.International journal of clinical pharmacology and therapeutics 12/2014; 53(01). DOI:10.5414/CP202076 · 1.04 Impact Factor