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Title of Journal: Cancer Chemother Pharmacol

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Abbravation: Cancer Chemotherapy and Pharmacology

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Springer-Verlag

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DOI

10.1007/s10461-010-9692-1

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1432-0843

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Prediction of human pharmacokinetics and tissue di

Authors: Beom Soo Shin Jürgen B Bulitta Joseph P Balthasar Minki Kim Yohan Choi Sun Dong Yoo
Publish Date: 2010/11/11
Volume: 68, Issue: 2, Pages: 465-475
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Abstract

The PK of apicidin was characterized in rats and mice after iv bolus injection and distribution to various tissues was determined in rats following iv infusions at steady state The developed models were prospectively validated within rat and within mouse and by scaling from rat to mouse using data after multiple iv injections Human PK was predicted by the physiologically based modeling using intrinsic clearance data for humans from in vitro experimentsThe Cls predicted for human 98 ml/min/kg was lower than those found in mice 1169 ml/min/kg and rats 616 ml/min/kg and the Vss predicted for human 19 l/kg was less than in mice 20 l/kg and rats 25 l/kg Consequently the predicted t 1/2 was longer in human 23 h than in mice and rats 04 and 09 h respectively The highest concentrations of apicidin were predicted in liver followed by adipose tissue kidney lung spleen heart arterial blood venous blood small intestine stomach muscle testis and brain

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