In Vivo Metabolism
In vivo metabolism studies are critical to the development of your compounds. Select from flexible metabolism studies and services, ranging from high throughput PK screening of compound libraries through definitive dose linearity and escalation/tolerability ahead of safety assessment or your IND/CTA filing. We also offer formulation bridging studies, experience with bioequivalence and biosimilars, as well as radiolabel distribution, excretion and metabolite identification.
- Global network of in vivo sites to offer fast study starts and maximum flexibility
- Thousands of dose initiations annually at global sites
- Experience with standard and non-standard animal models
- Variety of study types from high throughput to standard to definitive and investigative/R&D
In addition to offering a full suite of in vivo metabolism studies required to answer regulatory questions, we provide assistance with regulatory consutling or writing assistance for regulatory documentation.
Many sponsors also work closely with us to gain advice on which investigative studies to select or which studies would best target mechanistic insights for their compounds.
PK and PK/PD
High throughput screening, formulation screening, non-GLP/GLP, dose escalation/linearity, pharmacodynamics, tolerability, investigative and much more . . .
Get specific regulatory advice for your bioequivalence and biosimilar work. Our experts provide insight and guidance for appropriately powered study designs, as well as submission-ready data and reports, complete with statistics.
Stock & Client-Owned Colonies
We maintain colonies of non-naïve dogs and NHPs across global sites for both large and small molecule development in order to offer quick study starts. In addition to our colonies, clients sometimes choose to use a dedicated client-owned colony for intact and surgical (BDC, PVC, CSF) options. Tracking of molecule class (small and large molecules) enables efficient and sustainable animal re-use as part of our 3R philosophy.
Surgery & R&D
The in-house, dedicated surgical team can work directly with you on studies involving surgical modification. Choose from a standard offering or innovate with the team to perform R&D.
Oral, IV, subcutaneous, intramuscular, intrathecal, intranasal, dermal, and topical ocular routes of administration are utilized to determine the absorption, distribution, metabolism, and excretion of a radiolabeled compound.
We provide the expertise to custom-design and conduct your mass balance studies using 14C, 3H, 125I, 111In, and 131I, or other non-traditional radioisotopes.
The utilization of a radioisotope can provide specific ocular biodistribution information for your test article from selected ocular tissues. Get unrivalled expertise conducting radiolabeled ocular studies using ocular specific dose routes (topical, intravitreal, intracameral, superchoroidal, subretinal); animal species with tissue collection as well as quantitative autoradiography and microautoradiography end points.
Radiopharmaceuticals & Radiotherapeutic Agents
Get custom distribution, excretion and metabolism studies using gamma, beta and alpha radioisotopes and imaging agents for your radiopharmaceutical needs. All studies are performed to the applicable Federal Nuclear Regulatory Commission (NRC) or state-issued radiation license requirements..
Quantitative Whole Body Autoradiography (QWBA)
Distribution of therapeutic agents in the whole body or anatomical substructures can be determined through the use of low‑ or high‑energy emitting radioisotopes, including 3H, 14C, 125I, 131I, 35S, and 99Tc. Industry-leading global QWBA scientists produce quantitative results and qualitative images to depict distribution, retention/accumulation and elimination of a radiolabeled compound over time.
In addition to working with many preclinical test species, our scientists also work with tumor models and specific organs or anatomical areas of interest such as fetal organs, placental transfer models, joints or ocular tissues.
Preclinical tissue distribution data can be used to calculate human dosimetry estimations and enable human mass balance clinical studies using your radiolabeled compound in one of our clinical research units across the globe.
Human radiolabeled absorption, metabolism, and excretion (human AME) studies provide
- definitive information about mass balance and routes of elimination,
- a complete understanding of a drug's metabolism structure (including a comparison of human and animal metabolites to determine whether additional animal testing is warranted), and
- a determination of the ratio of parent drug to metabolite(s) in circulation.
In order to correctly identify hAME, our team of nuclear pharmacists, radiation safety committee members, medical doctors, and DMPK scientists work together with clients and sponsors to develop customized study designs that follow requirements from global regulatory authorities [e.g., FDA (including MIST, ICH) and EMA] for using a radiolabeled test compound. Merging scientific and regulatory components are critical to successful execution of a human AME study.
The ability to quickly analyze samples is key to a hAME study. In the United States, our shared campus in Wisconsin between the phase 1 clinical unit and the DMPK radioanalysis laboratory allows delivery of real-time radioanalysis results to manage subject-to-subject variability and facilitate timely subject release. In the UK, DMPK labs and clinical sites have hospital collaborations to successfully complete patient human AME studies in addition to normal healthy volunteers.
We've conducted more than 350 human AME studies, garnering decades of experience to guide successful study execution.
We use modeling of radiation exposures to support human absorption, metabolism, and excretion (hAME) clinical trials of radiolabeled molecules.
Dosimetry scientists use preclinical tissue distribution data to calculate dosimetry parameters in conjunction with applicable regulations and guidelines that govern human dosimetry, including the International Commission on Radiological Protection (ICRP), the US Food and Drug Administration (FDA), and the World Health Organization (WHO).
Our scientific team determines a safe radioactive dose level to be administered during the human radiolabeled mass balance and pharmacokinetic (PK) study.
The radioactive dose level and calculated radiation exposures to individual tissues and the whole body may be submitted to institutional review boards and ethics committees across the US and Europe for approval to conduct a human radiolabeled clinical study.
- Cassette and discrete dosing
- Intravenous (bolus, infusion)
- Oral (gavage, capsule/tablet, diet)
- Dermal, Intradermal
- Subcutaneous (bolus, infusion)
- Inhalation, Intranasal
- R&D upon request
- Blood (plasma, serum)
- Excreta (urine, feces)
- CSF (serial survival, terminal)
- Lacteal excretion
- Synovial fluid
- Serial biopsies:
- Bone marrow
- Lymph nodes
- R&D upon request