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Pharmacokinetics and tissue distribution of Kendine 91, a novel histone deacetylase inhibitor, in mice

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Abstract

Purpose

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.

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Acknowledgments

This work was supported by the Departamento de Educación, Universidades e Investigación, Gobierno Vasco (IT-407-07 and IT-324-07) and by the Spanish Ministerio de Ciencia e Innovación (Grants CTQ2007-67528 and CSD 2007-00006).

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Correspondence to José Luis Pedraz.

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Otaegui, D., Rodríguez-Gascón, A., Zubia, A. et al. Pharmacokinetics and tissue distribution of Kendine 91, a novel histone deacetylase inhibitor, in mice. Cancer Chemother Pharmacol 64, 153–159 (2009). https://doi.org/10.1007/s00280-008-0857-9

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  • DOI: https://doi.org/10.1007/s00280-008-0857-9

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