Relationships between in vitro and in vivo biotransformation of drugs in humans and animals: pharmaco-toxicological consequences.
Given the crucial role played by hepatocytes in the detoxification/toxification processes of drugs, these cells have been increasingly used during the last decade in various pharmaco-toxicological areas. The majority of these studies have, however, dealt with animal cells, although examples of failures in the extrapolation of the data to man are frequent. This drawback, together with the ethical considerations in performing in vivo experiments, makes the application of the human hepatocyte model critical in the preclinical evaluation of new compounds. However, before making extensive use of these promising tools for prospective pharmaceutical research, one must ensure that they can generate data that correlate well with those obtained in vivo. This is only possible through extensive studies on drugs showing a variety of phase I and phase II metabolic pathways in hepatocytes from different species, including man, and comparison with in vivo data. Providing this validation step is undertaken, the use of such systems in drug research and development may greatly enhance the rational design of safe and effective drugs, allowing savings in time, cost and test materials as well as minimizing the use of animals.
de Sousa
G
G
INSERM/Centre de Recherches INRA, Antibes, France.
Florence
N
N
Vallès
B
B
Coassolo
P
P
Rahmani
R
R
D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism* / Q000633:toxicity; D001549:Benzamides / Q000378:metabolism* / Q000633:toxicity; D001711:Biotransformation; D004285:Dogs; D000882:Haplorhini; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020912:Moclobemide; D051381:Rats; D017207:Rats, Sprague-Dawley; D012189:Retrospective Studies; D013045:Species Specificity; D015215:Zidovudine / Q000378:metabolism* / Q000633:toxicity
D000928:Antidepressive Agents; D001549:Benzamides; D015215:Zidovudine; D020912:Moclobemide