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Xenobiotica
the fate of foreign compounds in biological systems
Volume 37, 2007 - Issue 1
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Original

Prediction of pharmacokinetics of CS-023 (RO4908463), a novel parenteral carbapenem antibiotic, in humans using animal data

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Pages 91-102 | Received 18 Aug 2006, Accepted 19 Sep 2006, Published online: 12 Jul 2010
 

Abstract

The pharmacokinetics of CS-023 (RO4908463, formerly R-115685), a novel parenteral carbapenem antibiotic, in humans was successfully predicted using the data collected from mice, rats, rabbits, and dogs; while inclusion of the monkey data led to a significant underestimation of the total plasma clearance (CL). Double logarithmic plots of CL and distribution volume at the steady-state (Vss) vs. body weight in four animal species were linear with high correlation coefficients; and the predicted CL and Vss values in humans agreed well with the observed values after administration of CS-023 by an intravenous drip infusion for 30 min. The plasma concentration–time profile in humans, which was predicted using a bi-exponential equation fitted to a complex Dedrick plot of the animal data, approximated the observed profile. An underestimation of CL caused by including the monkey data in a prediction is quite likely due to the net tubular reabsorption in monkeys, but not at least in rabbits, dogs, and humans.

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