PHARMACOLOGICAL/TOXICOKINETIC AND ADME STUDIES

 

Pharmaco/toxicokinetic studies are conducted in order to get information about Absorption, Distribution in tissues, Metabolism and Excretion (ADME) of the test substance and its possible metabolites, in order to investigate its possible toxicity and target organs.

These studies provide very useful information on the test substance such as:

•Determination of the plasma concentration profile over time after administration;

•Identification of key pharmacokinetic parameters, such as half-life, clearance, volume of distribution and bioavailability;

•Definition and optimization of the therapeutic regimen: to define optimal route, doses and frequencies of administration in order to maximize the therapeutic efficacy and to minimize side effects;

•Determination of the No Observed Adverse Effect Level (NOAEL) and of the Lowest Observed Adverse Effect Level (LOAEL).

BIODISTRIBUTION STUDIES

Biodistribution studies are essential for the preclinical and clinical evaluation of a drug or of a therapeutic substance. These studies examine the distribution of a drug within the body after administration, providing crucial information about the safety, efficacy, and potential side effects of the treatment.

The main objectives of biodistribution studies are to:

•Determine which organs and tissues accumulate the drug and to quantify its accumulation by identifying target organs and potential sites of toxicity;

•Determine how long the drug remains in different organs, providing information about the potential need for repeated administration or changes in dose;

•Evaluate whether the distribution of the drug changes with the dose administered.

Biodistribution studies are conducted in compliance with GLP standards and international guidelines by the Bioanalytical and Molecular Biology units, which also performs the development and validation of the most suitable analytical methods, using specific techniques appropriate to the nature of the analyzed pharmaceutical products (HPLC, LC-MS for conventional drugs, Real-time PCR for vaccines based on nucleic acids and ATMPs).

Biological matrices processed

•Plasma samples

•Tissues

•Organs (i.e. liver, kidney, lung, muscle, etc.)

Reference guidelines

OECD Test 417: Toxicokinetics

ICH S3A- 3B: Toxicokinetics and Pharmacokinetics

EMEA/CHMP/GTWP/125459/2006: Guideline on the non-clinical studies required before first clinical use of gene therapy medicinal products

ICH S12: Nonclinical Biodistribution Considerations for Gene Therapy Products