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Studies provide an understanding of the biotransformation that a substance undergoes after its introduction into the body during its lifetime in the organism. Valuable data that is generated in various closely related species such as rodents (mice, rats), rabbits, dogs or monkeys enable prediction of both the metabolism and PK in humans. ChemDiv's animal pharmacology labs provide maximum flexibility in selecting adequate animal platform and study design. All studies are performed in accordance with a Statement of Work (SOW) that is developed jointly with the project sponsor to meet specific study objectives and to meet required regulatory guidelines.
METABOLIC STABILITY/METABOLYTE PROFILING
- Plasma, Hepatocytes, Microsomes, S9 Fraction (With multiple species: rodent, monkey, dog, human)
- Disappearance of main compound
- Identification of metabolic products
- CYP450 Inhibition (Fluorescence, LC/MS-MS)
- Primary screen, IC50, mechanism (competitive, non-competitive)
- 96/384-well plate format for HTS (fluorescence readout)
- Broad set of human recombinant cytochromes
PHARMACOKINETICS
- Single dose: IV, IP, PO
- Multiple time-points, triplicates
- 0.5 - 1 ml samples collected in EDTA-tubes
- 6 - 8 time points
Extensive Pharmacokinetic Support
ChemDiv provides comprehensive and flexible pharmacokinetic (PK) and toxicokinetic (TK) support of non-clinical drug development and has extensive scientific and regulatory experience in:
- Toxicokinetic analyses integrated into toxicity study reports
- Single-dose and repeat-dose PK studies
- PK and pharmacodynamic (PD) modeling
BIOAVAILABILITY (HPLC/MS)
Blood samples are analyzed to generate drug and/or metabolite concentration profiles over time. Urine and other tissue samples can also be used to track the drug tissue distribution and excretion. Basic PK parameters (e.g.: AUC, Cmax, tmax, elimination half-life, volume of distribution, clearance, oral bioavailability) are calculated together with fundamental statistics.
AUTOMATED PLATFORMS
API 2000 LC/MS/MS System with Turbo Ion Spray Source; Agilent 1100 HPLC system with UV/VIS Detector Flowcell; API 160 LC/MS System; Schimadzu 10AVp HPLC System with UV/VIS Detector; Gilson 215 autosampler; Evaporative Light Scattering Detector (ELSD) Sedex.
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