ADME Pharmacokinetics Studies

저자：   업로드：2017-09-07  조회수：

Absorption, Distribution, Metabolism and Excretion

• Absorption ‐ Route of Drug Delivery

– Where absorbed?

• Distribution ‐ Where does the drug go, where does it need to go and what are the implications?
• Metabolism Metabolism ‐ This will occur and could impact several several variables variables.

– Could be used to your advantage ‐ Prodrugs.

• Excretion – How is the drug eliminated?
• Pharmacokinetics is concerned with the variation in drug concentration with time as a result of absorption, metabolism, distribution and excretion

– Drug dose, route of administration, administration, rate and extent of absorption, absorption, distribution distribution rate (particularly to site of action) and rate of elimination.

– Pharmacokinetics may be simply defined as what the body does to the drug.

– Pharmacodynamics defined as what the drug does to the body.

in vivo ADME Services
We conduct a range of studies in rats and mice (other species are possible), including:

• Pharmacokinetics including dosing via i.v., oral, subcutaneous, intraperitoneal or intramuscular routes
• Calculation of basic PK parameters
• Bioavailability following dosing by any of these routes
• Metabolism studies, including metabolite identification (mass spectral and/or after enzymatic incubations)
• Recovery of parent drug and/or metabolites in urine, faeces or bile
• Tissue distribution studies, including dosing with nonradiolabelled or radiolabelled (supplied by the Sponsor)versions of the investigational drug

in vitro ADME Services
We conduct in vitro screening including:

• Metabolic stability screening or profiling due to Phase I (CYP450) or Phase II (glucuronidation / sulfonation) processes
• Studies conducted using cryopreserved hepatocytes (pooled human or male or female animal), microsomes or S9 as appropriate
• Identification of CYP450 isoforms responsible for metabolism using recombinant human CYPs
• Isolated perfused rat liver – TetraQ-ADME has many years experience with this model
• Caco-2 cell in vitro absorption studies

Drugs are specifically designed using ADME principles; however, chemicals for commercial use are not designed with any guidelines targeting ADME.

Absorption

There are four main routes of exposure:

    - Inhalation through the respiratory system: a chemical in the form of a gas, vapor or particulate that is inhaled and can be excreted or deposited in the respiratory system.
    - Dermal through skin or eye contact.
    - Ingestion through the gastrointestinal system: Absorption through the digestive tract. Ingestion can occur through eating or smoking with contaminated hands or in contaminated work areas.
    

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