In vivo ADME

Tissue distribution/QWBA

Quantitative whole-body autoradiography (QWBA) uniquely assesses the pattern and time course of drug distribution in a whole-body image. QWBA images allow the visualisation and quantification of radioactive material (unchanged drug and metabolites) in tissues and organ substructures. The data generated can relate adverse events (e.g., histopathological findings in toxicology studies) to the presence or absence of drug-related material in relevant tissues. Combined with mass balance study results in preclinical species, QWBA distribution data provide input for dosimetry calculations and predict radiological exposure in humans, preparing for radiolabelled mass balance studies (hADME) as required by regulatory authorities. 

We have experience conducting single and repeated dose QWBA studies with 14C- and 3H-radiolabelled compounds. Our smart and cost-effective QWBA designs evaluate exposure to drug-related material in blood and tissues (including regional distribution within certain organs), elimination rates, localisation at the site of action (e.g., dermal, tumour, or blood-brain barrier penetration), placental transfer, and binding to melanin-containing tissues and structures.

Placental transfer

The use of drugs during pregnancy raises concerns about potential fetal exposure and possible adverse effects due to their distribution and accumulation in fetal tissues and organs. Assessing whether a compound can cross the placental barrier is an important part of the drug safety package. Such data are typically obtained from QWBA studies using pregnant rodents to determine potential exposure and risk to the fetus.

AME (mass balance, metabolite profiling and identification)

Radiolabelled absorption, metabolism and excretion (AME) studies in rodent and non-rodent species are crucial for non-clinical drug development, assessing the disposition of unchanged drugs and total drug-related material. These data are vital for safety and efficacy assessments and regulatory submissions, aiming to determine the radioactive dose excreted in urine, faeces, and expired air (mass balance). Both animal mass balance and QWBA data inform dosimetry calculations for safe radioactive doses in human mass balance (hADME) studies. 

We have many years of experience in conducting mass balance studies in rodent and non-rodent species, adhering to the 3R principle (replace, reduce, refine) to deliver maximum information with cost-effective designs. Radioactivity is quantified by liquid scintillation counting (LSC) in blood, plasma, urine, faeces, bile, and, if needed, expired air, various tissues, and carcasses. Our biotransformation team generates metabolite profiles in all matrices using off-line scintillation counting after chromatographic (UPLC) separation and fraction collection, allowing quantification of low-level radioactive signals. Metabolite structures are elucidated by high-resolution mass spectrometry (HR-MS) according to predefined quantitative thresholds relative to the radioactive dose.

Biliary excretion

We offer comprehensive studies to investigate biliary excretion as part of rodent mass balance studies using radiolabelled drug candidates. These studies characterise the excretion pathways and rate, including the detection and identification of metabolites eliminated into bile. Once a substance is excreted by the liver into bile and subsequently into the intestinal tract, it can either be eliminated via faeces or reabsorbed—a process known as enterohepatic circulation. This process can significantly influence the pharmacokinetics of a compound, potentially prolonging its elimination half-life. Evaluating enterohepatic circulation is therefore crucial for assessing a drug candidate's safety and efficacy. Our tailored study designs in rodents provide detailed insights into hepatobiliary elimination, helping you understand the excretion pathways and metabolism of your drug candidate, and determine the extent of enterohepatic circulation of drug-related material.

Species and routes of administration

We work with a variety of animal species (mice, rats, dogs, and genetically modified animals, e.g. mice or rats). Our available routes of administration include intravenous (bolus or infusion) and oral, and other routes of administration are available upon request.

Matrices

We analyse a wide range of biological matrices, including blood, plasma, serum, urine, faeces, bile, expired air and various organs and tissues.

Reports

We deliver standardised, submission-ready reports using our templates or customised reports tailored to your specific needs and requirements.