title: Single Dose Oral and Intravenous Pharmacokinetics and Tissue Distribution of a Novel Hesperetin Derivative MTBH in Rats.
abstract: BACKGROUND
  MTBH, a novel hesperetin derivative, possesses in vivo hepatoprotective effects against carbon tetrachloride (CCl4)-induced acute liver injury in Institute of Cancer Research (ICR) mice.
  
  
  OBJECTIVE
  This study investigated the pharmacokinetics and tissue distribution of MTBH and its conjugated metabolites in rats after a single dose of MTBH.
  
  
  METHODS
  Male Sprague-Dawley (SD) rats were orally administered (25, 50, 100 mg/kg) or intravenously administered (25 mg/kg) MTBH and blood samples were withdrawn at specific times. Moreover, after a single oral dose of MTBH (200 mg/kg), tissues (heart, liver, spleen, lung, kidney, stomach, intestine, brain and muscle) were collected at scheduled time points.
  
  
  RESULTS
  The concentration of MTBH in plasma and tissues was assayed by HPLC before and after hydrolysis with β-glucuronidase or sulfatase. The glucuronides/sulfates were extensively present in the plasma, moreover, the free form was detectable in the plasma, but in a small amount equivalent to nearly 0.85-1.46 % of the amount of glucuronides/sulfates, the absolute bioavailability of MTBH was approximately 31.27 %. In tissues, the free form appeared in all tissues examined, with trace amount in brain and muscle, and considerable concentration in stomach and lung. Glucuronides/sulfates were the major forms in intestine, kidney and liver, whereas not detectable in heart, brain and muscle. The liver and intestine were found likely to accumulate MTBH at a high concentration among all tissues.
  
  
  CONCLUSIONS
  The free form of MTBH was present in the circulation and all assayed organs, whereas its glucuronides/sulfates were the major forms in plasma and intestine, kidney and liver after a single dose.
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei, 230032, China.
authors.forename: Chenlin
authors.initials: C
authors.lastname: Shen
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei, 230032, China.
authors.forename: Zhengyue
authors.initials: Z
authors.lastname: Qian
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei, 230032, China.
authors.forename: Ruonan
authors.initials: R
authors.lastname: Chen
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei, 230032, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Meng
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei, 230032, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Hu
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei, 230032, China.
authors.forename: Zhaolin
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei, 230032, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei, 230032, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei, 230032, China.
authors.forename: Chaojie
authors.initials: C
authors.lastname: Hu
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei, 230032, China. shchlin520@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001711:Biotransformation; D002252:Carbon Tetrachloride Poisoning / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D020719:Glucuronides / Q000097:blood / Q000378:metabolism; D006207:Half-Life; D006569:Hesperidin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D007275:Injections, Intravenous; D008297:Male; D020011:Protective Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013431:Sulfates / Q000097:blood / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D020719:Glucuronides; D020011:Protective Agents; D013431:Sulfates; D006569:Hesperidin; C013015:hesperetin