Pharmacokinetics (PK) describes how the body affects the absorption, distribution, metabolism, and excretion (ADME) processes of specific xenobiotics/chemicals or their metabolites after administration. Various dose routes can be performed, including intravascular administration (intravenous bolus or infusion) and extravascular administration (oral, subcutaneous, and intraperitoneal injection). It is of great reference significance to do administration method studies in the pre-clinical stage when selecting a clinical administration route. In vivo, pharmacokinetic studies play an essential role in new drug discovery and development stages.
The early stage of new drug research and development (R&D) mainly focuses on the target validation, lead compounds discovery, and optimization affirmed by routine in vivo pharmacokinetics and specific tissue distribution experiments. Its purpose is to understand the drug structure-activity relationship (SAR) and guide the dose selection for late pharmacodynamics studies. Therefore, project quality and turnaround time (TAT) are significant.
In the late stage of new drug development , a study mainly focuses on preclinical candidate compounds selection and IND (Investigational New Drug) filing. The requirements for relevant in vivo experiments and biological sample analysis are stricter as possible compounds move onto the development stage. More detailed and well-targeted in vivo pharmacokinetic experiments are required for this phase of research. For example, dose-escalation studies are necessary to explore the linear relationship between dose and dose-response, investigate the effects of different formulations or different salt forms on in vivo exposure, in vivo pharmacokinetics, and cross-over experiments.
WuXi AppTec DMPK Service Department is committed to providing a comprehensive R&D platform for in vivo PK experiments, assisting new drug R&D projects with effective in vivo research methods, and providing accurate and efficient solutions to cope with all the challenges that occur in the new drug development.
The protocol is designed specifically to fulfill clients' needs and their experiment purposes, including formulation screening, dose and sampling time point setting, administration route, and sample matrix selecting. In formulation screening studies, the compound stability and solubility in its solvent are measured based on its physicochemical properties before in vivo study starts.
Dosing strategies can be discrete dosing or cassette dosing (N-in-1 cassette). Cassette dosing is an attractive procedure for high-throughput screening large numbers of candidate compounds (up to 4 candidate compounds and one reference compound) in drug discovery through assessing their pharmacokinetic properties. Administration routes include but are not limited to intravenous, oral administration, intraperitoneal injection, intramuscular injection, subcutaneous injection, intraventricular administration, intranasal administration, and intratracheal administration. Sampling duration can be set at 24 hours or above according to compound characteristics and project requirements.
The routine matrices are collected from in vivo pharmacokinetic experiments, including plasma, serum, brain, cerebrospinal fluid, bile, urine, feces, liver, gastrointestinal, and other specific tissues and fluids. If it is necessary to investigate the drug concentration of a specific tissue, the tissue or tissue fluid can be collected from blood sampling at different time points to obtain the ratio of tissue drug concentration to plasma concentration (for example, collecting brain and blood to assess the brain/plasma drug concentration ratio).
We are always committed to providing a comprehensive in vivopharmacokinetic service platform for our clients. We focus on client demands to establish the corresponding experimental system and pharmacokinetic screening strategies, including data interpretation and data application. We are eager to satisfy all the in vivo pharmacokinetics assessing requirements proposed by our clients.
Identification of PK issues
In Vivo screening and compounds ranking
Proof of Concept (POC) based on compound exposure
The screen on a specific “soft-spot.”
Fully assess ADME properties in animals
Provide support for identifying safety assessment species
Provide a basis for predicting safety dose for further clinical studies
Present declared data (detailed preclinical test compound characterization) to regulatory authorities
Demonstrate that compounds are promising and can be conducted for further safety and efficacy evaluation studies
Seek and verify suitable dosage and dose routes for human
Determine DMPK properties under the target dosage regimen (dosage and dose route have been decided)
Reasonable analysis on the safety and efficacy studies presented from the test compound
All animal facilities are accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International).
Animal facilities in Shanghai and Suzhou have acquired PHS Animal Welfare Assurance. Animal facility in New Jersey have acquired OLAW assurance.
This team has experienced preclinical formulation screening research experts and is equipped with advanced instruments which enable selecting suitable preclinical formulation within 24 hours.
This team has accumulated technologies and experience of more than 15 years. They continue updating existing technicals and developing industry-leading new technologies, such as mouse saphenous vein, rat jugular vein puncture, and other continuous blood sampling methods.
This team is experienced in many difficult and complex technicals such as aseptic surgical operation and sample collection. They had overcome many technical difficulties, such as lymphatic cannulation in rats and biliary cannulation in mice.
This team is experienced and professional in veterinary and animal care to fully ensure animal welfare.
The team continues to develop new capabilities and has made achievements in inhalation administration, intraventricular administration, in vitro release testing, and in vitro skin permeation study.
Short lead-timeEfficient operation leads to rapid result delivery. Early screening study: 5-7 days; IND study: 2 weeks.
Sufficient animal resourcesA well-organized animal supply ensures timely project implementation. Long-term supply agreements with world-class suppliers guarantee this.
Comprehensive experiment typesAble to conduct studies from discovery to development stages, elect species from rodent to non-rodent, perform a variety of administration routes, and complete multiple sample collections to meet the diverse needs proposed by the clients.
Reliable experimental resultsProvide a complete set of pharmacokinetics evaluation services meeting the FDA, OECD, and NMPA Investigational New Drug (IND) application requirements, with high data reproducibility.
Professional solutionProvide experienced data trouble-shooting analysis and professional solutions.
Advanced instruments and equipmentThe wide application of an industry-leading automated cage washer, automated blood sampling instrument, automated liquid workstation, and IT intelligent tools help ensure the efficient execution of customer projects and obtain stable and reliable experimental results.