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Pharmacokinetics and pharmacodynamics of three oral formulations of curcumin in rats

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Abstract

Curcumin (CUR) is a major component of turmeric Curcuma longa, which is often used in food or as a dietary supplement. The purpose of this preclinical study is to investigate the acute pharmacokinetic and pharmacodynamic (PK/PD) profiles of two commercially marketed CUR products (GNC and Vitamin Shoppe) and a CUR powder from Sigma in female rats. Plasma samples were collected at specific time points and analyzed for CUR and its metabolite curcumin-O-glucuronide. RNA was extracted from leukocytes and analyzed for the expression of Nrf2-mediated antioxidant genes Nrf2, Ho-1, and Nqo1 by qPCR as selected PD markers. CUR PK was characterized by a 2-compartment model (2CM) after intravenous (IV) or oral administrations. Compared to IV CUR, the absolute bioavailability (F) of CUR for GNC (GC) is 0.9%, Vitamin Shoppe (VC) is 0.6% and Sigma (SC) is 3.1%. Pharmacodynamically, all three formulations showed induction of antioxidant Nrf2, Ho-1 and Nqo1 gene expression in rat leucocytes. PK/PD modeling of CUR’s effect on antioxidant gene expression was well captured by an indirect response model. Physiologically based PK modeling and simulation using GastroPlus described the observed PK data reasonably well. In summary, our current study shows that the absolute oral bioavailability of the parent CUR was very low for all three formulations. However, despite the low CUR plasma concentrations, all three oral CUR formulations displayed PD response in the induction of Nrf2-mediated antioxidant genes, suggesting the potential of oral CUR contributing to the overall health beneficial effects of oral CUR.

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Acknowledgement

We thank all the members of Kong lab for their suggestions and helpful discussions in the preparation of this manuscript. This work was supported in part by institutional funds, R01AT007065 from the National Center for Complementary and Integrated Health (NCCIH) and the Office of Dietary Supplements (ODS), and R01AT009152 from the National Center for Complementary and Integrative Health (NCCIH).

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  1. Lujing Wang and Wenji Li have contributed equal to this work.

Authors and Affiliations

  1. Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Room 228, 160 Frelinghuysen Road, Piscataway, NJ, 08854, USA

    Lujing Wang, Wenji Li, David Cheng, Yue Guo, Renyi Wu, Ran Yin, Shanyi Li, Hsiao-Chen Kuo, Rasika Hudlikar & Ah-Ng Kong

  2. Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA

    Lujing Wang, David Cheng, Yue Guo & Hsiao-Chen Kuo

  3. Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, People’s Republic of China

    Wenji Li

  4. Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225001, People’s Republic of China

    Wenji Li

  5. Environmental and Occupational Health Sciences Institute, Piscataway, NJ, 08854, USA

    Hilly Yang & Brian Buckley

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  1. Lujing Wang
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Wang, L., Li, W., Cheng, D. et al. Pharmacokinetics and pharmacodynamics of three oral formulations of curcumin in rats. J Pharmacokinet Pharmacodyn 47, 131–144 (2020). https://doi.org/10.1007/s10928-020-09675-3

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