title: Preclinical pharmacokinetics and ADME characterization of a novel anticancer chalcone, cardamonin.
abstract: Cardamonin (CRD), a chalconoid obtained from several medicinal plants of Zingiberaceae family, had shown promising potential in cancer prevention and therapy. For further development and better pharmacological elucidation, we performed a series of in vitro and in vivo studies to characterize its preclinical pharmacokinetics. The study samples were analyzed using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high performance liquid chromatography-ultra violet (HPLC-UV) methods. CRD is partially soluble (<10 μM) and possess high permeability (>0.2 × 10-4 cm/sec). It is moderately bound to plasma proteins (<50%). It shows partitioning in red blood cell (RBC) compartment with the partition coefficient between RBCs and plasma (KRBC/P) of 0.95 at 0 min to 1.39 at 60 min, indicating significant but slow RBC uptake. In mice, CRD is poorly absorbed after oral administration with 18% oral bioavailability. It possesses high clearance, short mean residence time, and high volume of distribution in mice. It exhibited multiple peak phenomena both after oral and intravenous administration and is excreted both as conjugated and unchanged CRD in bile. It is majorly excreted in faeces and negligibly in urine. The preclinical absorption, distribution, metabolism, and excretion data are expected to succour the future clinical investigations of CRD as a promising anticancer agent. Copyright © 2016 John Wiley & Sons, Ltd.
authors: Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India.|Academy of Scientific and Innovative Research, New Delhi, India.
authors: Swati
authors: S
authors: Jaiswal
authors: Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India.|Academy of Scientific and Innovative Research, New Delhi, India.
authors: Mahendra
authors: M
authors: Shukla
authors: Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India.|Academy of Scientific and Innovative Research, New Delhi, India.|Department of Pharmaceutics and Drug Delivery, The University of Mississippi, Mississippi, USA.
authors: Abhisheak
authors: A
authors: Sharma
authors: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Raebareli, India.
authors: Nagarjun
authors: N
authors: Rangaraj
authors: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Raebareli, India.
authors: Kalpesh
authors: K
authors: Vaghasiya
authors: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Raebareli, India.
authors: Mohd Yaseen
authors: MY
authors: Malik
authors: Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India.|Academy of Scientific and Innovative Research, New Delhi, India.
authors: Jawahar
authors: J
authors: Lal
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism; D047188:Chalcones / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D011485:Protein Binding; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods; D030521:Zingiberaceae / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001798:Blood Proteins; D047188:Chalcones; C436747:cardamonin
keywords: absorption; bioavailability; distribution; excretion; metabolism