Final answer:
A Chronic Rodent Bioassay is a long-term study performed on rodents like mice or rats to explore the pharmacokinetics of a drug, specifically how the drug is absorbed, distributed, metabolized, and excreted. It is an essential component of non-clinical drug development and utilizes methods like UV, MS, and MS/MS for bioanalytic support.
Step-by-step explanation:
The term Chronic Rodent Bioassay refers to a long-term study conducted on rodents, typically to assess the chronic toxicity or carcinogenic potential of a substance over a major portion of the rodent's lifetime. These rodent bioassays are essential components in the non-clinical phase of drug development. They provide important data on drug pharmacokinetics, including absorption, distribution, metabolism, and excretion (ADME) of chemical entities. For pharmacokinetic characterization, rodents (such as mice and rats) are used as the first animal species for testing due to their cost-effectiveness and the smaller amount of test compound required. These studies often involve multiple dosages (both oral and intravenous) to understand the bioavailability of a drug and its metabolites, and can highlight potential issues in ADME, such as low absorption or high clearance that could result in undesirable pharmacokinetic profiles.
In vivo pharmacokinetic studies in rodents are supported by bioanalytic methods, including UV, MS, and MS/MS for quantifying the parent drug and identifying metabolites in biological matrices. The process is meticulously planned with specific time points for blood samplings, such as 0-5 hours after dosage, to obtain metrics like AUC (Area Under the Curve), Cmax (maximum concentration), tmax (time to reach Cmax), clearance, and duration of exposure. These pharmacokinetic studies play a crucial role in drug discovery and are reviewed according to FDA guidelines related to MIST (Metabolites in Safety Testing) and DDI (Drug-Drug Interactions) to monitor the relative exposure of metabolites.