Michael Kennedy

Publications (2)6.19 Total impact

• Article: 17α-alkynyl 3α, 17β-androstanediol non-clinical and clinical pharmacology, pharmacokinetics and metabolism.

  Clarence Ahlem, Michael Kennedy, Theodore Page, David Bell, Evelyn Delorme, Sonia Villegas, Chris Reading, Steven White, Dwight Stickney, James Frincke
  [show abstract] [hide abstract]
  ABSTRACT: 17α-ethynyl-5α-androstane-3α, 17β-diol (HE3235, Apoptone) is an orally bioavailable synthetic analogue of 3β-androstanediol, that is active in rodent models of prostate and breast cancer, and is in Phase IIa clinical trials for the treatment of early- and late-stage prostate cancer. In preparation for clinical studies, nuclear hormone receptor and P450 interactions for HE3235 and major metabolites were characterized in vitro, and pharmacokinetics and metabolite profiles were studied in rodents, dogs, and monkeys. Four-week safety studies conducted in rats and dogs indicated a substantial margin of safety for clinical use, and no evidence of electrocardiographic or neurological effects, although anorexia, thrombocytopenia, and hypokalemia were identified as potentially dose-limiting toxicities at superpharmacological exposures. Pharmacokinetics and drug metabolism have been studied in prostate cancer patients.
  Investigational New Drugs 02/2012; 30(1):59-78. · 3.36 Impact Factor
• Article: Novel components of the human metabolome: the identification, characterization and anti-inflammatory activity of two 5-androstene tetrols.

  Clarence N Ahlem, Theodore M Page, Dominick L Auci, Michael R Kennedy, Katia Mangano, Ferdinando Nicoletti, Yu Ge, Yujin Huang, Steven K White, Sonia Villegas, Douglas Conrad, Angela Wang, Christopher L Reading, James M Frincke
  [show abstract] [hide abstract]
  ABSTRACT: Two natural 5-androstene steroid tetrols, androst-5-ene-3β,7β,16α,17β-tetrol (HE3177) and androst-5-ene-3α,7β,16α,17β-tetrol (HE3413), were discovered in human plasma and urine. These compounds had significant aqueous solubility, did not bind or transactivate steroid-binding nuclear hormone receptors, and were not immunosuppressive in murine mixed-lymphocyte studies. Both compounds appear to be metabolic end products, as they were resistant to primary and secondary metabolism. Both were orally bioavailable, and were very well tolerated in a two-week dose-intensive toxicity study in mice. Anti-inflammatory properties were found with exogenous administration of these compounds in rodent disease models of multiple sclerosis, lung injury, chronic prostatitis, and colitis.
  Steroids 10/2010; 76(1-2):145-55. · 2.83 Impact Factor