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AAALAC Accredited In Vivo Animal ADME Studies

In Vivo Pharmacokinetic (PK) Studies

In vivo pharmacokinetic (PK) studies provide exposure (AUC) data by measuring drug concentration in plasma of treated laboratory animals at successive time points; ‘hot’ (radiolabeled compound) studies can yield more complete information than cold studies by including metabolite data in addition to parent drug concentration.

By performing in vivo PK studies, developers are looking to characterize the pharmacokinetic profile of a compound and to inform efficacy of a drug by validating that it will reach necessary concentration levels in plasma and tissue. Drug concentration in plasma is analyzed to characterize the pharmacokinetic properties of the drug, such as absorption and clearance. 

Our Approach to In Vivo ADME / PK Studies

A PK study is one of the basic in vivo ADME package elements performed by our sister lab in Tokai, Japan. The Drug Development Solutions Center  has accumulated over 50 years’ experience performing radiolabeled compound experiments, radioisotope (RI) synthesis, and purity checks for pharmaceutical companies as the leading in vivo ADME CRO in Japan. The facilities areaccredited by AAALAC International 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.

In an in vivo PK study, multiple Sprague-Dawley rats are dosed with radiolabeled compound to provide more complete information about a drug’s pharmacokinetics than a ‘cold’ study yielding only parent compound exposure data. This can be achieved by comparing the concentration of radiolabeled compound in the plasma (representative of both parent and metabolites) to the concentration of parent compound. Radiolabeled parent compound is measured using LC-MS, while total reactivity is measured by LSC. If there is a large difference in concentration between the total radioactivity and the parent compound, it indicates that the compound is extensively metabolized. Conversely, if there is almost no difference in concentration between total radioactivity and parent compound, it can be judged that the compound is metabolically stable.

The PK measurement process includes the establishment of an appropriate analytical system, administration to clinically relevant species, sampling of blood/plasma, and quantification. Data from PK studies can be compared to data from protein binding and DDI studies to give the drug developer information necessary to evaluate a drug compound’s overall fate/disposition.

Pharmacokinetic PK studies rely on precise animal study data for a complete ADME package

In Vivo PK Study Features & Options

  • High-precision determination of radioactivity in plasma and blood cells 
  • Flexible study design
  • Standard study includes 3 animals and 14 time points
  • Short turnaround times for subsequent analytical method development
  • Calculation of PK parameters
    • Cmax
    • tmax
    • t1/2
    • AUC0-t
    • AUCint
    • CL
    • VD
    • BA
  • All experimental procedures are executed to the highest standards of animal welfare, are compliant with AAALAC International, and approved by our Institutional Animal Care and Use Committee (IACUC)
  • Instrumentation and study design can accommodate many radionuclide options and routes of administration (see table below)
  • Radiolabeled or non-labeled compound can be analyzed
  • Microsampling and microdosing options available
  • Immunological methods (RIA and ELISA, etc.) available for the measurements of drug concentration, biomarkers and/or neutralizing antibodies
  • High-resolution LSC and LC-MS quantification, HPLC and UPLC analysis available
    • Xevo TQ-XS
    • QTRAP 6500+/5500
    • API 5000/4000 
Tissue CapabilitiesRadionuclidesAnimal SpeciesMatricesRoutes of Administration
Adrenal Gland
Brain
Lung
Liver
Intestine
Kidney
Muscle
Pancreas
Retina
Skin
Spleen
Thyroid Gland
Tumor
14C
3H
125I
33P
35S
51Cr
111In
55Fe
59Fe
65Zn
75Se
90Y
153Gd
Rat
Mouse
Rabbit
Dog
Monkey
Minipig
Animal Plasma
Serum
Whole Blood
Urine
Brain
Skin
Synovial Membrane
Cerebrospinal Fluid
Human Plasma
Serum
Urine
Horny Layer of Skin
Oral
Intravenous
Transdermal
Subcutaneous
Intramuscular
Intratracheal
Instillation
Intrarectal
Intraduodenal

*Other tissue types, species, or routes of administrations may be available upon request

Regulatory Compliance in PK Studies

Studies conducted at Drug Development Solutions Center also meet or exceed standards required by regulatory authorities, including FDA and EMA, just as with our Kansas City campus. While in the United States, there is no method by which an institution can claim certified compliance with Good Laboratory Practice (GLP) standards, the PMDA can grant certification following an inspection that approves a Japanese facility as GLP-compliant in specific practices. The Drug Development Solutions Center has this certification for all bioanalytical services, a critical component of many animal studies. The Center is also certified by AAALAC International for ethical use of animals in research so you can be sure services exceed quality standards required by the FDA upon IND or NDA submission. 

By contracting a Drug Development Solutions Center study through SEKISUI XenoTech, we make it easy for North American and European clients to benefit from the years of experience our Tokai team has built. Read more in our blog about how we make it easy to work with the Drug Development Solutions Center for your in vivo nonclinical services.

Which Studies & Why

PK is one of our standard offerings in an in vivo ADME package– Read our quick guide outlining regulatory expectations and basic study outlines for other components

In Vivo Bioanalysis

Access ADME™

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

“examining drug parent or metabolites in excreta or biomaterial can help drug developers understand important ADME and PK properties of their drug candidate