In Vitro Drug Metabolism & ADME

The use of in vitro assays to define drug metabolism in animals and humans prior to in vivo studies is a pivotal step in defining the drug-like properties of new drug candidates.

BRI provides in vitro drug candidate metabolism screening, metabolite characterization, induction, inhibition and ADMET studies performed under GLP in conformance with USFDA, USEPA, OECD regulations and guidelines.

RAPID IN VITRO ADME SCREENING

In vitro rapid metabolic stability in liver microsomes species:

– RLM, DLM, HLM, or other species
– Typical 1 µM incubation over 5 time points over 120 min
– LC/MS/MS assay of parent drug disappearance
– Data within one-week from receipt of compounds

Materials

– Cryopreserved human primary hepatocytes (intact system)
– microsomes (mainly oxidative pathways)
– S9 (soluble oxidases, hydrolyases, transferases phase II)
– Purified rCYPs

GLP IN VITRO METABOLISM STUDY

Species

– Human, Cyno monkey, dog, rat, mouse and others

Study Designs

– Proprietary assessment of drug candidate solubility in microsome or hepatocyte
buffers to ensure dose linearity
– Metabolic stability & determination of CLint
– Metabolite profile, structural elucidation & inter-species 14C-labeled study
– CYP450 pathway phenotyping
– Metabolic inhibition of major CYPs (Determination of IC50, Ki, KI/kinact)
– Metabolic induction screening
– Covalent binding screening and rank-ordering
– Metabolic induction screening
– Covalent binding screening and rank-ordering
– Anaerobic metabolism in human fecal homogenate