The main goal of preclinical toxicokinetic (TK) studies is to establish a correlation between a candidate compound’s concentration or dose and its potential toxicity. TK studies are conducted during the drug development process as part of non-clinical toxicology or safety studies. As such, our TK study offering is a GLP bioanalytical service complementing in vivo animal phases of development.
Data obtained from the early non-GLP exploratory toxicology studies help a drug developer understand more about the compound before definitive (GLP) toxicology studies, and TK data from the definitive toxicology studies provide the detailed systemic exposure profile essential for dosing considerations prior to first-in-human (FIH) studies and other clinical phases. TK data can also help to reduce the number of laboratory animals used in a drug’s development, aligning with international goals of the 3Rs (replacement, reduction and refinement) of animals used in research.
Analytical Follow-Up to Toxicology Studies
In addition to the core in vivo ADME and radiolabeling services at our partners in Japan, the Drug Development Solutions Center, we can also offer analytical support for your in vivo toxicokinetic studies. Extensive experience, state-of-the-art instrumentation, and Good Laboratory Practices (GLP) certification for bioanalytical services enable the team to deliver reliable results.
Determination of toxicokinetic profile in toxicity studies
Selection of dose, form, and route
Toxicity evaluation
Toxicological mechanisms
Comparison between human and animals
TK Analysis at the Drug Development Solutions Center
Between the Drug Development Solutions Center’s superior analytical capabilities and an external partner specializing in animal toxicology to carry out the experiments, we can help you achieve high-quality, GLP-compliant toxicokinetic data. We have bioanalytical capabilities both in Tokai, Japan, and in Kansas City for biological matrices of treated animals, and then specific TK parameters are defined using the latest version of WinNonlin at the Tokai facility.
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 CRO in Japan. Their facilities are certified by AAALAC International to meet compliance with ethical requirements upheld by FDA, EMA, and PMDA for all animal studies, and GLP certified for all bioanalytical services.
After developing and validating the analytical methods for samples obtained in safety studies, the measurement of drug concentration in biological samples is conducted under international GLP standards. Data conversion service is also available, where TK data are presented in accordance with SEND (Standard for Exchange of Nonclinical Data required for submissions to FDA).
For large molecule drugs, a TK study can also provide data about the formation of anti-drug antibodies and their neutralizing properties to inform dosing considerations.
TK Analysis Features & Options
High-sensitivity determination of drug concentration in biological matrices from treated animals
Elucidation of metabolite profiles and structure via LC-MS/MS
Calculation of TK parameters using WinNonlin (v 8.1)
Specific parameters such as Cmax, Tmax, AUC, t1/2, clearance (CL), volume of distribution (VD), etc.
Microsampling options available with corresponding high-sensitivity analytical capabilities
Immunological methods and analysis
Bead-based suspension array
ELISA
Regulatory Compliance
Toxicokinetic studies and follow up analyses are designed according to Japanese Pharmaceutical and Medical Devices Agency (PMDA) standards as well as recommendations described in most recent publications by international regulatory authorities, including the Guideline on Bioanalytical Method Validation in Pharmaceutical Development (Notification No. 0711-(1) of the Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau, Ministry of Health and Welfare, 2013) and the Good Laboratory Practice Standards for Non-clinical Safety Studies on Drugs (Ministry of Health and Welfare Ordinance No. 21, 1997).
While in the United States, there is no method by which an institution can claim certified compliance with GLP standards, the PMDA can grant certification to facilities in Japan following an inspection for GLP-compliance in specific practices. The Drug Development Solutions Center has this certification for all its in vivo bioanalytical services, including TK analysis.
Instrumentation Capabilities
We use only highly-sensitive analytical instruments and immunological techniques to accurately determine drug concentration for a TK service:
Gupta, P.K. (2016). “Principles and basic concepts of toxicokinetics.” Fundamentals of Toxicology. 87-107. doi:10.1016/B978-0-12-805426-0.00009-3
Horii, I. (1998). “Advantages of toxicokinetics in new drug development.” Toxicology Letters. 102-103, 657-664. doi:10.1016/s0378-4274(98)00281-1
See our other analytical capabilities
You can get quick, high-quality bioanalysis for your clinical plasma, blood or urine samples at our Kansas City laboratory, or for animal studies at the Drug Development Solutions Center all bioanalysis is GLP-certified by the PMDA. Find out more about our In Vivo Metabolite Identification and Characterization
A strong reputation for superior in vivo ADME and radiolabeling services defines our partner lab, the Drug Development Solutions Center. Read more about their core in vivo studies and radioisotope (RI) synthesis for your pharmaceutical compounds
