Creative Biolabs has worked extensively on a wide variety of ADME assays. As part of our in vitro ADME service, we provide high-quality in vitro metabolism service to evaluate the metabolic fate of your compounds to meet your demands.

After a drug entering the body for a certain time, it will be eliminated either by excretion or by metabolizing to one or more metabolites. Metabolism routes of a drug can significantly affect its safety and efficacy. If a drug is eliminated via a single metabolic pathway, individual differences may largely influence the metabolic rates and lead to large differences in drug and metabolite concentrations in the blood and tissue. Dosing adjustments to different individuals may be necessary to achieve the safe and effective use of the drug.

Metabolism usually occurs in the liver, and in vitro drug metabolism is measured by the activity of enzymes contained in the cytochrome CYP450 superfamily. The concomitant drug may cause interactions of inhibiting or inducing the CYP450 enzymes. Creative Biolabs provides services of CYP reaction phenotyping for common drug metabolizing tissue: liver. Besides, we also focus on extrahepatic tissues, such as intestine, kidney, lung or skin. These assays are performed using multi-available enzyme source and analyzed with our high-quality UPLC/HR-MS-instrumentation.

In Vitro Metabolism Studies Figure 1. Characteristics of essential and nonessential metabolites in E. coli metabolism. (Kim et al. 2007)

Our services include:

Metabolite Profiling and Identification

Creative Biolabs provides a variety of matrices for metabolite profiling and identification, including liver microsomal incubations, hepatocyte incubations, S9 incubations, recombinant enzymes as well as other in vivo samples. We measure compound degradation, isolated metabolites and elucidate the chemical structural by a variety of structure determination methods. The UPLC/high-resolution-MS/MS techniques are the major tool for metabolite identification both qualitatively and quantitatively.

Metabolic Stability

Metabolic stability studies are measuring the disappearance rate of a chemical compound. The half-life, in vitro clearance results can be used to predict hepatic clearance and extraction ratio and also to evaluate dose, toxicity, oral bioavailability, etc. Creative Biolabs provides UPLC/high-resolution-MS technology for liver microsomal incubations, hepatocyte incubations, S9 incubations, recombinant enzymes and plasma to assess metabolic stability. A comprehensive metabolite profiling and identification services are also available from the very same analytical data.

Extrahepatic Metabolism

Creative Biolabs assesses the cytosolic enzyme activity by incubation of extrahepatic samples (gastrointestinal tract, kidneys, lungs, skin and brain) with the drugs of interest.

Reactive Metabolite Analysis

Creative Biolabs provides reactive metabolites characterization service to avoid unexpected idiosyncratic drug-induced toxicity. We provide detecting method by nucleophilic chemical trapping such as glutathione tri-peptide (GSH; most often used), potassium cyanide (KCN; used for hard electrophiles) or semicarbazide, which can form stable adducts with many reactive species and then detected by UPLC-TOFMS methods. Multivariate data analysis (MDA) was then conducted to screen trapped reactive metabolites.

Drug-Drug Interactions (DDI)

DDI is closely related to therapeutic efficacy loss and unacceptable toxic side effects. Our featured DDI evaluating platform has been designed according to up-to-date scientific progress and regulatory recommendations. Overall information of DDI potencies and mechanism insights can be obtained by our integrated assay portfolio:

For more detailed information, please feel free to contact us or directly sent us an inquiry.

Reference

  1. Kim PJ, Lee DY, Kim TY, et al. (2007). Metabolite essentiality elucidates robustness of Escherichia coli metabolism. Proceedings of the National Academy of Sciences of the United States of America 104(34):13638-13642. doi:10.1073/pnas.0703262104.

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