Pre-clinical evaluation of Rh2 in PC-3 human xenograft model for prostate cancer in vivo: formulation, pharmacokinetics, biodistribution and efficacy.
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.
Musende
Alain G
AG
The Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada. alainmus@gmail.com
Eberding
Andy
A
Wood
Catherine
C
Adomat
Hans
H
Fazli
Ladan
L
Hurtado-Coll
Antonio
A
Jia
William
W
Bally
Marcel B
MB
Guns
Emma Tomlinson
ET
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
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