Toxicology / Drug Safety

IDEXX BioAnalytics offers a range of bioanalysis services to detect early adverse effects resulting from drug administration at a preclinical level. IDEXX BioAnalytics stems from IDEXX, the animal health industry's leading diagnostics company in the world, so you can rely on our extensive experience in animal diagnostics & research services. Some of our tests are proprietary and can be run on multiple animal species (mouse, rat, cat, dog, pig, NHPs, etc) to detect early cardiac, renal or liver toxicity issues. Additionally, GLP histopathology services run by recognised IDEXX BioAnalytics experts complement the extensive range of our toxicity biomarkers. Furthermore, a range of haematology, biochemistry and analytical chemistry tests are also available. Some useful tests in these areas are described below.

Cardiotoxicity

Cardiopet® proBNP, Ultrasensitive Troponin I (us-TnI), Creatine Kinase MB (CK-MB) and histopathology are useful tools for cardiac toxicity assessment.
The N-terminal prohormone of brain natriuretic peptide (Nt-proBNP) increases even when no signs of heart failure are present, which shows its high sensitivity to predict cardiotoxicity after treatment. As heart disease progresses, the chambers become more stretched and BNP is released in greater quantities. Cardiopet® proBNP measures Nt-proBNP, allowing you to quantitatively track the progression of the disease.

Cardiac troponin I (cTn I) is a sensitive and specific marker of myocardial injury. The troponin concentration can be thought of as a quantitative measure of the degree of injury sustained by the heart. cTn I is becoming the serum biomarker of choice for monitoring potential drug-induced myocardial injury in both clinical and preclinical studies. The utility of cardiac troponins has been mainly demonstrated following the administration of antineoplastic drugs and beta-sympathomimetic, so they are useful tools to assess drug-induced cardiac toxicity in laboratory animal species. IDEXX BioAnalytics offers us-cTn I, the ultrasensitive method for cardiac Troponin I detection. 

Creatine Kinase MB (CK-MB), like cTn I, also indicates the presence of injury-associated necrosis of myocardial cells and has provide useful hints in drug development.

Liver Toxicity

Detecting Drug-Induced Liver Injury (DILI) from the very early stages of pharmaceutical development is vital for drug developers. Among the existing biomarkers, ALT and AST are general indicators of hepatocellular injury. Increases in Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Total Bilirubin are often part of a cholestatic DILI pattern. The range of tests available is complemented by Gamma Glutamyltransferase (GGT), Glucose dehydrogenase (GLDH) and cholinesterase, being all these useful tools to detect liver disfunction. Bile acids are also important markers, since those present in serum represent the bile acids not cleared by the liver due to impaired hepatic function. A decrease in urobilinogen in urine levels may also a sign of biliary obstruction.

Finally, perturbations in the coagulation cascade are frequently associated with acute liver toxicity, since the liver is the primary site of synthesis of nearly all coagulation factors. Thus, clotting time will increase with severe liver injury. The status of the coagulation system can also be checked with tests such as prothrombin time (Quick’s test) and activated partial thromboplastin time (APTT). 

 Kidney toxicity

Although many forms of Drug Induced Kidney Injury (DIKI) damage do not produce symptoms until late during the drug administration, there are warning signs, such as blood urea nitrogen (BUN) and creatinine levels falling outside the normal range (bearing in mind that both their reference values can vary between different species).

Other parameters measured to assess renal function are: the (lowered) glomerular filtration rate (GFR), Phosphate (PO4), Potassium (K), Protein (total), Sodium (Na), Chloride and other analytes. Routine haematology analysis is also recommended. IDEXX SDMA test is a useful tool to asses glomerular filtration rate (GFR) and detect changes to kidney function much earlier than with creatinine and BUN alone.

Symmetric Dimethyl Arginine (SDMA) is excreted from the kidneys; therefore, as kidney function or GFR decreases, SDMA increases. Studies have shown a very strong correlation between SDMA and GFR (R2 of 0.82 in cats; R2 of 0.85 in dogs). The benefit of using SDMA along with creatinine, which typically increases above the reference interval only after a 75% reduction in GFR, is that SDMA increases when there is on average a 40% decrease in GFR. In some cases, SDMA increases earlier when there is 25% reduction of GFR, representing 25% loss of kidney function.

*In bold, IDEXX BioAnalytics tests and services available

 
 

*In bold, IDEXX BioAnalytics tests and services available