title: Pre-clinical evaluation of Rh2 in PC-3 human xenograft model for prostate cancer in vivo: formulation, pharmacokinetics, biodistribution and efficacy.
abstract: OBJECTIVE
  This study assesses the pharmacokinetics, biodistribution and efficacy of ginsenoside Rh2 as a single agent administered in a novel oral dosage formulation.
  
  
  METHODS
  A novel oral dosage formulation of Rh2 has been described. Rh2 levels in blood and tissues following administration to nu/nu nude mice were determined by high performance liquid chromatography tandem mass spectroscopy. Efficacy was determined in an established PC-3 human prostate cancer model.
  
  
  RESULTS
  Rh2 administered at a dose of 120 mg/kg exhibited a peak plasma concentration of 19.0 +/- 2.0 microg/ml. Rh2 levels were measurable in prostate and tumor tissues, with as much as 0.3% of the administered dose being detected in tumors. This formulation exhibited no measurable toxicity as judged by weight loss or changes in serum levels of aspartate aminotransferase, alanine aminotransferase, and creatinine. This dose engendered a significant delay in PC-3 tumor growth, an increase in apoptotic index, and a decrease in tumor cell proliferation.
  
  
  CONCLUSIONS
  Rh2 is a stable compound that can be formulated for oral gavage. Pharmacokinetics studies demonstrate its ability to be absorbed following oral administration. Future studies will assess the pharmacokinetics of Rh2 when administered in combination with docetaxel.
authors.affiliation: The Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada. alainmus@gmail.com
authors.forename: Alain G
authors.initials: AG
authors.lastname: Musende
authors.forename: Andy
authors.initials: A
authors.lastname: Eberding
authors.forename: Catherine
authors.initials: C
authors.lastname: Wood
authors.forename: Hans
authors.initials: H
authors.lastname: Adomat
authors.forename: Ladan
authors.initials: L
authors.lastname: Fazli
authors.forename: Antonio
authors.initials: A
authors.lastname: Hurtado-Coll
authors.forename: William
authors.initials: W
authors.lastname: Jia
authors.forename: Marcel B
authors.initials: MB
authors.lastname: Bally
authors.forename: Emma Tomlinson
authors.initials: ET
authors.lastname: Guns
mesh_terms: D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000825:Animal Structures / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D003404:Creatinine / Q000097:blood; D000077143:Docetaxel; D004355:Drug Stability; D036145:Ginsenosides / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use; D014018:Tissue Distribution; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D036145:Ginsenosides; D019394:Ki-67 Antigen; D012997:Solvents; D043823:Taxoids; D000077143:Docetaxel; C055305:ginsenoside Rh2; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase