Pharmacokinetics and tissue distribution of Kendine 91, a novel histone deacetylase inhibitor, in mice.
OBJECTIVE
The present investigation was undertaken to characterize the pharmacokinetics and oral bioavailability of Kendine 91 in mice and to compare it with other HDAC (histone deacetylases) inhibitors.


METHODS
After administration of a single intravenous dose (10 mg/kg) or a single oral dose (50 mg/kg) blood and tissues samples were collected and analysed by HPLC/MS/MS.


RESULTS
Elimination half-life was higher than that of SAHA (5.87 vs. 0.38 h after intravenous (IV) administration and 10.29 versus 0.75 h after oral administration). Absolute oral bioavailability was found to be 18%. Total body clearance (7.72 l/h/kg) was greater than the hepatic blood flow of 5.4 l/h/kg in mice and larger than glomerular filtration rate in mice (0.84 l/h/kg). Tissue levels and distribution volume indicate a high capacity of Kendine 91 to distribute into tissues.


CONCLUSIONS
This preliminary pharmacokinetic evaluation prompts us to believe that it is worth pursuing further development of Kendine 91 as an anticancer drug.
Otaegui
Dorleta
D
Organic Chemistry Department, Faculty of Chemistry, University of the Basque Country, Edificio Joxe Mari Korta, San Sebastián, Spain.
Rodríguez-Gascón
Alicia
A
Zubia
Aizpea
A
Cossío
Fernando P
FP
Pedraz
José Luis
JL
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics*; D005260:Female; D005919:Glomerular Filtration Rate; D006207:Half-Life; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011758:Pyrroles / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution; D000077337:Vorinostat
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011758:Pyrroles; C540813:kendine 91; D000077337:Vorinostat