Disposition of vorinostat, a novel histone deacetylase inhibitor and anticancer agent, in preclinical species.
The disposition of vorinostat, an anticancer agent, was investigated in rats and dogs. Vorinostat possessed high serum clearance, a short elimination half-life and low oral bioavailability in both species. The renal route played an important role in the elimination of drug-related material and vorinostat was eliminated primarily by metabolic biotransformation.
Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA. punam_sandhu@merck.com
Punam
P
Sandhu
Paul A
PA
Andrews
Maribeth P
MP
Baker
Kenneth A
KA
Koeplinger
Eric D
ED
Soli
Thomas
T
Miller
Thomas A
TA
Baillie
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics*; D006207:Half-Life; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014018:Tissue Distribution; D000077337:Vorinostat
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat