2024.07.08
The Role of Liver Microsomes in Drug Metabolism
The liver is central to drug metabolism, with approximately 50-60% of marketed drugs being cleared through hepatic cytochrome P450 (CYP)-mediated pathways. In vitro drug metabolism studies focus on hepatocytes or subcellular liver fractions such as microsomes, cytosols, or S9 fractions, which are rich in specific enzymes. Liver microsomes, vesicles derived from the endoplasmic reticulum of liver cells and prepared through liver homogenization and differential centrifugation, contain high concentrations of key drug-metabolizing enzymes, including CYP and UDP-glucuronosyltransferase (UGT).
Advantages of Using Liver Microsomes
Liver microsomes provide a convenient and effective in vitro system for studying CYP-mediated metabolism. They offer a complete CYP enzyme environment, ensuring accurate kinetic measurements without interference from other metabolic processes or cellular uptake. Liver microsomes are essential for hepatic drug metabolism studies, metabolite profiling, metabolic stability assessments, metabolite identification, and CYP enzyme inhibition. Their ease of preparation and storage, suitability for high-throughput screening, and cost-effectiveness make them particularly advantageous in drug discovery.
Potential Applications of Liver Microsomes
Drug-Drug Interaction Assays: Essential for predicting adverse drug interactions.
Metabolic Stability Screening: Crucial for assessing compound stability.
CYP Enzyme Inhibition: Important for identifying potential inhibitors.
Enzyme Kinetics Studies: Key for understanding metabolic rates.
Metabolite Profiling and Identification: Vital for tracking metabolic fate.
High-Throughput Screening: Useful for early-stage compound screening.
Toxicology Assays: Necessary for evaluating compound safety.
MileCell's Metabolism-Qualified Pooled Animal Liver Microsomes
Liver microsomes from multiple species are essential for determining the in vitro intrinsic clearance of compounds. Using species-specific microsomes provides insights into interspecies differences in drug metabolism. Additionally, pooled liver microsomes from multiple donors minimize variability. MC's experienced hepatic product specialists have optimized liver microsome systems for in vitro drug metabolic stability studies, demonstrating excellent intrinsic clearance compared to other branded products. Our metabolic stability assays show that our animal liver microsomes present consistent activity across batches and inter-lots. Below are examples of metabolic stability in cynomolgus monkey and beagle dog liver microsomes.
