Comparison of metabolite formation for CYP specific substrates in human and rat lung S9 using single or pooled incubations.

摘要

In drug development it is necessary to understand the routes of metabolism using human and pre-clinical animal species in vitro systems to ensure effective planning of drug safety testing studies. For projects in which inhalation is the intended route of drug administration, it is imperative to investigate the metabolism using lung tissue in vitro (typically using lung S9). To ensure the metabolic competence of the CYPs (Cytochrome P450 enzymes) and other relevant drug metabolizing enzymes expressed in the lung tissue, incubations with CYP-selective substrates are performed, ensuring that relevant pulmonary CYPs are studied (Olsson et al., 2011). Pooling of substrates in a single control incubation is desirable to reduce the complexity and cost of experiments.