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AAALAC Accredited In Vivo Animal ADME Studies

Animal Mass Balance Studies for Preclinical Drug Development

In vivo mass balance studies are an important element of nonclinical drug development, to inform first in-human (FIH) studies and to uncover pieces of the pharmacokinetic (PK profile of a drug. Elucidating PK properties can help bridge activity and toxicity data to paint a full picture of a drug’s behavior in patient populations. Radiolabeled mass balance excretion studies in rodent or non-rodent toxicologically relevant species represent a standard part of the development process for drugs prior to clinical trials.

Mass balance data can demonstrate primary mechanisms of elimination and excretion from the body and proportion of parent drug converted to metabolite, shedding light on clearance mechanisms of a drug and its metabolites. Typical animal mass balance (excretion) studies measure excretion of radiolabeled parent compound and metabolites in urine, feces, and expired air, and if necessary can measure residual radioactivity in the carcass. Biliary excretion can also be measured in cases where more than 20% of radioactivity is seen in feces after oral dosing.

While clinical mass balance studies in humans provide the best predictive data for effect on patient populations, animal mass balance data is a necessary step in preliminary risk assessment and study design planning before administration to human volunteers. Regulatory agencies require both animal mass balance and QWBA data for dosimetry calculations to determine appropriate radiolabeled dose in human absorption, metabolism, and excretion (hAME) studies in Phase I clinical trials.

In vivo scientist at the Tokai Drug Development Solutions Center

Mass Balance Data Provides Critical Human AME Calculation Inputs

Mass balance data informs the total fate of drug-related material and is one of our standard in vivo ADME offerings performed by our sister lab in Tokai, Japan. The Drug Development Solutions Center has accumulated over 50 years’ experience performing radiolabeled (RI) experimentation, synthesis, and purity checks for pharmaceutical companies as the leading in vivo ADME CRO in Japan. The facilities are AAALAC-accredited to meet compliance with ethical requirements upheld by FDA, EMA, and PMDA for all animal studies– find out more about the Drug Development Solutions Center’s radiolabeled compound synthesis and in vivo ADME capabilities.

Capabilities of animal species, radionuclides, and routes of administration are outlined below:

ROUTES OF ADMINISTRATION RADIONUCLIDES ANIMAL SPECIES
Oral
Intravenous (administration or infusion)
Percutaneous
Subcutaneous
Intramuscular
Intracheal
Opthalmic
Colorectal
Intraduodenal
Nasal
Intraocular
Sublingual
Intrauterine
Intracerebral
Intravesical
Knee Joint
14C
3H
125I
33P
35S
51Cr
111In
55,59Fe
65Zn
75Se
90Y
153Gd
Rats
Mouse (including chimeric with humanized liver)
Rabbit
Dog
Monkeys
Miniature pig
Animal models of human disease (knockout models)

Standard Mass Balance Study Elements

  • Measurement of radioactivity in urine and feces and residual radioactivity in carcass 168 hours post-dose
  • Liquid scintillation counter (LSC) analysis of each sample for radioactivity quantification
  • Additional bile duct cannulation (BDC) can be performed in tandem with mass balance to determine biliary excretion
  • Remaining urine and feces conserved for Metabolite Identification

Related Content:

Access ADME™ is a growing repository for scientific resources organized by topic; find related scientific content covering in vivo ADME and pharmacokinetics on the In Vivo / Radiolabeling page.

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Which Studies & Why

Not sure which in vivo studies you should plan before your drug goes to first in-human (FIH) clinical trials? Read our quick guide outlining regulatory expectations and basic study outlines for each basic in vivo study we offer

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In Vivo ADME Science

Access ADME™ is your go-to repository for our scientists’ content relevant to radiolabeling and in vivo drug development, including information about regulatory expectations and expertise of our Tokai team

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