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Metabolite Profiling

Although metabolism of drugs, or xenobiotics in general, occurs in a variety of tissues – such as the intestinal wall, lung, kidneys, skin and blood – the liver is regarded as the major site of drug metabolism. Hepatocytes or liver microsomes are, therefore, a fast and cost-effective way to determine intrinsic clearance (CLint) of drug candidates.

These CLint determinations, along with other parameters including plasma protein binding and blood: plasma ratio, often allow a good prediction of in vivo hepatic clearance.

In order to mitigate against unacceptably high clearance, it is usually necessary to identify the major metabolic pathway(s) as well as the nature of the enzymes involved.

At Sygnature Discovery, we know that every drug discovery project is different.

Whether it is oral, intravenous or topical, the way a drug has been designed to be administered will affect the type of in vitro assays needed. Pro-drug strategies can avoid pre-systemic metabolism and help to deliver a drug to its target organ or site. All these approaches require specific in vitro experiments. Sygnature Discovery can help you choose, plan and execute the studies that add the most scientific value to your drug discovery project.

Sygnature Discovery offers a wide range of biological systems to determine in vitro and in vivo metabolic stability including primary cells, e.g. hepatocytes, tissue homogenates and tissue fractions, e.g. microsomes, mitochondrial preparations, S9 fractions and intestinal fluid from a variety of pre-clinical species and human.

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