Creative Animodel, as a preclinical contract research organization (CRO), has spent decades of efforts on toxicology. With experienced staff and professional platforms, we provide metabolism services to help clients accelerate the process of drug discovery and development.
An Overview of Drug Metabolism
The main purpose of drug metabolism is to promote the excretion by increasing hydrophilicity. Most drug metabolism occurs in the liver, while some drug metabolism occurs in the gut wall, lungs, or blood plasma. The metabolism of drugs can be divided into two phases. In phase I, involving in oxidation, reduction, oy hydrolysis, the parent drugs are converted into more polar metabolites. In this stage, the most common biochemical process is oxidation which is catalyzed by cytochrome P450 enzymes. The phase II metabolism involves conjugation of groups, like carboxyl, hydroxyl, amino, and sulfhydryl. The reactions are catalyzed by a variety of transferases, such as glutathione S-transferases (GSTs), methyltransferase, sulfotransferases.
Figure 1: Current knowledge of drug-metabolizing enzymes and drug transporters that operate in the human liver, kidney, and intestine (Yeung, 2014)
Available Metabolism Services
• Cytochrome P450 Reaction Phenotyping
Creative Animodel offers high-quality cytochrome P450 reaction phenotyping assays using expressed enzymes to identify which drug metabolizing isoforms are responsible for the metabolism of a test compound.
• Cytochrome P450 Induction
A compound that induces CYP450 enzymes can change the metabolism of other drugs, resulting in a loss of drug efficacy. Creative Animodel conducts professional CYP450 induction assays by assessing mRNA levels and catalytic activity in cultured human hepatocytes.
• Cytochrome P450 Inhibition
It is important to evaluate the potential possibility whether the compound inhibits a specific cytochrome P450 enzyme, which can lead to toxicity or adverse drug reactions. Creative Animodel provides reliable cytochrome P450 inhibition assays.
• Cytochrome P450 Time Dependent Inhibition
Creative Animodel provides different approaches to cytochrome P450 time dependent inhibition which can result in drug-drug interaction (DDI) or no-linear pharmacokinetics of drugs, including single point assay, IC50 shift assay and Kinact/KI assay.
• Cytochrome P450 Ki
Ki values are intrinsic inhibition constants. Creative Animodel offers cytochrome P450 Ki recommended by regulatory authorities to study the clinical relevance of reversible cytochrome P450 inhibition.
• UGT Assays
Uridine 5'-diphospho-glucuronosyltransferase (UDP-glucuronosyltransferase, UGT) are a family of enzymes involved in conjugation reactions of drug metabolism. Creative Animodel offers three essential UGT assays, including UGT reaction phenotyping, UGT induction, and UGT inhibition.
• Non-CYP Mediated Metabolism
Creative Animodel provides professional services about non-CYP mediated metabolism to help clients understand whether testing compounds are inductors or inhibitors in the metabolism of non-CYP enzymes, or which non-CYP enzymes involve in the metabolism of the testing compounds. Our non-CYP metabolising enzymes include flavin mono-oxygenases (FMO), monoamine-oxidases (MAO), N-acetyltransferases (NAT), aldehyde oxidase (AOX), carboxylesterases (CE), etc.
• PXR and AhR Nuclear Receptor Activation
The pregnane X receptor (PXR) and the aryl hydrocarbon receptor (AhR) are common nuclear receptors involved in the activity modulation of cytochrome P450 genes and the induction of drug metabolism. Creative Animodel offers PXR and AhR nuclear receptor activation services to identify the ability of testing compounds to modulate cytochrome P450.
With years of experience, Creative Animodel has conducted numerous toxicology assays. With state-of-the-art equipment and profound pharmaceutical knowledge, we can provide clients reliable metabolism services. If you have any questions or specific needs, please feel free to contact me.
Yeung C. K., et al. Effects of chronic kidney disease and uremia on hepatic drug metabolism and transport. Kidney international, 2014, 85(3): 522.