Extrahepatic Metabolism

BOC Sciences performs a variety of in vitro metabolism studies. Relying on a professional technical team, we provide extrahepatic metabolism services to measure the metabolism of drugs at extrahepatic sites.

Drug metabolism, also known as biotransformation, is one of the main ways drugs are eliminated from the body. There are two main steps in the metabolism of drugs in the body, namely phase I and phase II reactions. The first metabolic reaction (phase I reaction) includes oxidation, reduction, hydroxylation and hydrolysis. In the second step of metabolic reaction (phase II reaction), the drug or phase I reaction metabolites are combined with some endogenous substances or excreted from the body after methylation and acetylation. The liver is the main site of drug metabolism and contains many enzymes required for phase I and phase II metabolism. Certain drugs are also metabolized in extrahepatic tissues.

Extrahepatic tissues involved in drug metabolism include plasma, skin, brain, lung, kidney, gastrointestinal tract, etc. Different extrahepatic tissues have different metabolic characteristics due to differences in tissue anatomy and physiological structure. Drug-metabolizing enzymes are distributed in the microsomal and cytoplasmic fractions of different tissues. Microsomal enzymes control hepatic metabolism, while cytosolic enzymes control extrahepatic metabolism. BOC Sciences assessed cytosolic enzyme activity by incubating the drug with extrahepatic tissue samples.

Fig. 1 The drug-metabolic and elimination pathways (John N, 2018))

Extrahepatic Metabolite Analysis

The analysis method of extrahepatic metabolites is the same as that of liver metabolites. Various methods are used to measure the degradability of sample compounds, isolate metabolites, and determine chemical structures. Finally, qualitative and quantitative analysis of metabolites was carried out by means of high-precision resolution mass spectrometry or chromatography-mass spectrometry.

Extrahepatic Clearance

BOC Sciences offers metabolic stability services to measure the clearance, half-life and oral bioavailability of compounds from the body. Metabolic stability research is of great significance for the screening of superior compounds, guiding structure modification, predicting in vivo clearance rate, constructing IVIVC and estimating dosage. This assay can be used to assess drug clearance from the skin, intestinal microsomes, and plasma.

Drug Interaction Assays Related to Extrahepatic Metabolism

The important purpose of drug interaction research related to extrahepatic metabolism is to explore whether the drug may have a significant impact on the metabolic elimination of drugs that may be combined in medical diagnosis and treatment. Relying on a complete analysis system, BOC Sciences provides overall information on drug interactions related to extrahepatic metabolism through CYP inhibition or induction tests, UGT inhibition or induction tests, and response phenotype determinations.

Analysis of Reactive Metabolites Affecting Immune Cells

Drug metabolism may elicit immune cell responses. In most cases, reactive metabolites are bioinactivated, resulting in the drug changing from a fat-soluble compound to a water-soluble compound that is easily excreted. However, in cases of abnormal drug metabolism, reactive metabolites can lead to direct toxic effects or immune-mediated allergic reactions. The former is the combination of reactive metabolites with proteins or nucleic acids, causing cell necrosis or gene mutation. In the latter, reactive metabolites are covalently bound to cellular macromolecules as haptens to elicit an immune response. BOC Sciences offers reactive metabolite analysis to determine the effect of drug metabolism on immune cells.