The ADME services offered at Alliance Pharma are comprehensive and can support high throughput drug discovery research as well as more definitive studies intended to support your regulatory filings. We’ve recently shared some details about these services, particularly in relation to drug Absorption and Distribution. Of course, the ADME acronym also includes the important processes of Metabolism and Excretion.
Metabolism is arguably the most critical aspect of drug disposition. As such, in vitro metabolic stability is one of the most commonly used ADME assays and is intended to predict the rate at which a drug or compound is eliminated from the blood circulation via metabolic processes. Metabolism occurs primarily in the liver, but it can also occur in extrahepatic tissues like the intestine and kidney. Measurement of metabolic stability in vitro is typically used early in drug discovery to screen out undesirable compounds and to predict in vivo clearance in various species.
At Alliance, we routinely perform metabolic stability studies in different species using fresh and cryopreserved hepatocytes, liver microsomes, liver S9 fractions and liver cytosol. The study can also be performed in extrahepatic tissues, such as the intestine, brain, kidney, lung, and skin. Metabolic stability studies can also be used to uncover polymorphic metabolism liabilities, investigate and elucidate the metabolic pathways and profiles of a drug and identify the formation of toxic metabolites. Alliance has a team dedicated to the identification of metabolites formed during in vitro metabolism studies and high resolution mass spectrometers used explicitly to support these types of studies.
Potentially dangerous drug-drug interactions (DDI) due to enzyme induction and inhibition are also important to understand early in drug development. Administration of some xenobiotics results in a selective increase in the concentration of Phase I and Phase II metabolizing enzymes via receptor mediated induction pathways, or through stabilization of the proteins themselves. Enzyme induction becomes especially important when drugs with narrow therapeutic windows are co-administered with other drugs since the increased drug metabolism can result in a significant decrease in exposure and loss of therapeutic efficacy. Likewise, inhibition based DDIs can pose a significant safety risk due to the potential for substantial increases in drug concentrations that can expose acute toxicity and dangerous side effects. At Alliance, our Drug Metabolism team has the tools you need to mitigate DDI risks at various stages of drug development.
Thank you for allowing us to be your trusted partner. You’ll find even more details on our website, and we invite you to contact us to discuss ADME assays in more detail. We can be reached at 610-296-3152 or firstname.lastname@example.org.