| Cytochrome P450 isoform-specific in vitro methods to predict drug metabolism and interactions | ||
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In all research on human beings or employing human in vivo studies or human tissue-derived methods, such as microsomes or isolated primary cells, one must take good care of fulfilling the demands of ethical issues. All such studies have to be accepted by the local ethics committee.
Whenever performing studies on humans, it is extremely important to take into account the Declaration of Helsinki. In vitro studies also warrant careful consideration of what research procedures are acceptable for human-derived material. In Finland, there is currently no legislation covering such commercial purposes. However, as the techniques are widely used and there are academic or commercial groups providing preclinical studies for drug development companies, this issue will become increasingly important. Today, the use of human surplus tissue has to be approved by the local ethics committee.
Animal studies are quite expensive and because of the marked differences in the drug-metabolising enzymes between humans and the test species, it is reasonable to perform in vitro testing to select the species best able to characterise human metabolism for an NCE. The use of animal liver microsomes, homogenate or isolated hepatocytes for first studying the metabolic patterns of the NCE will reduce both costs and the number of animals needed for preclinical drug development.
The use of human tissue-derived in vitro systems in affinity screening and metabolic stability studies gives more accurate information about the in vivo situation than the use of test species treated with the compound under study. Still, because of the demands of the authorities, some testing for pharmacokinetics and toxicity has to be performed on animals. Human-derived in vitro systems are increasingly reducing the number of animals needed for such tests. For the time being, these animal tests are necessary, but careful planning and effective use of the in vitro methodology can reduce the use of animals in many research fields.