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VOL. 73 (1), 5-26, 2007 IN VITRO INVESTIGATION OF DRUG METABOLISM AND TOXICITY...

potential interindividual variations in metabolic rates or metabolite
profile. The utility of cultured hepatocytes for this purpose was
examined by investigating the metabolism of a model compound,
aceclofenac, both in vitro and in vivo. The in vitro metabolism of the
compound was studied in hepatocyte cultures obtained from human
patients who, after clinical recovery, received a sub-clinical dose of
the drug to examine the metabolism in vivo (presence of metabolites
in urine) (74). A remarkable similarity between metabolic profile
and the extent of aceclofenac in vitro and in vivo metabolism was
found for each donor. These results support the idea that cultured
human hepatocytes are a good approximation to anticipate in vivo
metabolic profile of a drug, and back the validation process needed
by this experimental model to be considered as a simplified tool
to study drug metabolism and drug interactions. Moreover, the
interindividual variations in drug metabolism also become evident
in in vitro studies.

ACKNOWLEDGEMENTS

The authors thank the financial support of the ALIVE Foundation,
the Fondo de Investigaciones Sanitarias from Instituto de Salud
Carlos III of Spain (03/0339), and the European Commission (LSHB-
CT-2004-504761 and LSHB-CT-2004 512051).

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