Abstract
Toxicokinetics is defined as “the generation of pharmacokinetic data, either as an integral component in the conduct of nonclinical toxicity studies or in specially designed supportive studies, in order to assess systemic exposure. These data may be used in the interpretation of toxicology findings and their relevance to clinical safety issues” (ICH Guidance Toxicokinetics 1994). The ratio of drug exposure in animals at the no observed adverse effect level (NOAEL) and in humans at the expected therapeutic dose is one of the precautionary principles to determine the risk benefit profile of pharmaceuticals. For this ratio the expressions “safety ratio” and “safety margin” were also used. It is usually based on human plasma AUC exposure (animal/human AUC ratio); however, depending on the mode of action or whichever is smaller, the ratio can also be based on the maximum concentration in plasma (animal/human C max ratio).
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Lehr, KH. (2011). Toxicokinetics and Safety Ratios. In: Vogel, H.G., Maas, J., Gebauer, A. (eds) Drug Discovery and Evaluation: Methods in Clinical Pharmacology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-89891-7_21
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DOI: https://doi.org/10.1007/978-3-540-89891-7_21
Publisher Name: Springer, Berlin, Heidelberg
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