Pharmacokinetics describes the uptake of drugs by the body, the biotransformation of the drugs and their metabolites in the tissues, and the elimination of the drugs and their metabolites from the body over a period of time, and includes the distribution of bioactive substances within the various compartments present in an animal or human body, especially high-molar-mass polymers that cannot cross endothelial or epithelial physiological barriers.
Explicitly, pharmacokinetics is the study of drug absorption, distribution, metabolism and elimination (ADME). Typically, the first in vivo experiment during an oral drug discovery project would be a single IV bolus dose in a preclinical species. This would already allow the determination of key PK parameters such as AUC, Cmax, t½, Vss and clearance. After a test compound has successfully passed this first PK hurdle, further PK studies are used to build a more detailed picture of all aspects of ADME. Oral PK, in combination with the above IV data allows the determination of oral bioavailability (F).Low oral F can be caused by poor absorption and/or high first-pass hepatic elimination. Collection of urine or bile allows calculation of renal and biliary clearance and identification of metabolites.
The following example shows typical pharmacokinetic profiles after a single intravenous (IV) or oral (PO) bolus:
We offer complete support for the in vivo evaluation of compound properties, including:
- Typical PK Design (mice, rat, dog, monkey)
- Single, Multiple and Cassette Dose PK
- In vivo Crossover Studies for Bioavailability (F )
- Administration Routes (i.v., p.o., i.p., s.c., i.m. etc)
- Rat Carotid artery & Jugular Vein Cannulation
- Mouse Serial blood collection from saphenous vein
- PK/PD studies in Normal and Disease Animals
- Allometric Dose Prediction and PK Optimization
- Effects of Food, Gender and Formulation Type on
- PK Tissue Distribution and Mass balance
- Non-GLP Tox (single dose, Single dose escalating, repeat dose)
- TK/MTD (Toxicokinetics/Maximum Tolerated Dose)
- AAALAC Accredited Facilities
- Standard Formulation & Specific Formulation Development
A typical protocol design for PK might take the form of:
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