bin inhibitor, napsagatran (Figure 9.5). Allometric scaling based on pharmacokinetic data from the rat, rabbit, monkey and dog overestimated total clearance, non-renal clearance and volume of distribution in man by 3-, 7- and 2-fold respectively. As napsagatran is not metabolized in vitro or in vivo, this would suggest that species differences in the transport proteins involved in the clearance of napsagatran, especially the protein responsible for hepatic uptake across the sinusoidal membrane, compromise the kinetic extrapolations from animals to man. Notably, amongst the individual species investigated, the monkey was most predictive of human clearance and volume of distribution .
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