Preclinical Development

The ultimate goals of preclinical studies are to accurately model, in animals, the desired biological effect of a drug in order to predict treatment outcome in patients (efficacy), dosing and administration route (pharmacokinetic, bioavailability), and to identify and characterize all toxicities associated with a drug in order to predict adverse events (safety) for informed risk assessment.

In vivo assays are developed in accordance with the guidelines of European Union Directive 2010/63/EU on the protection of animals used for scientific purposes. Studies are performed in the Animal Facilities of the Center of Biomedical Investigation of the University of Granada (Granada, Spain).

Preclinical Development

  • LC-MS/MS Agilent 1290-API4000 (SCIEX)
  • LC-HRMS Agilent1290-Triple TOF5600 SCIEX
  • Liquid handlers equipped with on-deck accessories; Freedom EVO, Tecan; Biomek FX and i7, Beckman, Echo® Acoustic Liquid Handling System, Beckman; EvolutionP3, PerkinElmer; and software specifically designed to automate sample preparation procedures

See also Bioanalytical Services Section

  • We prepare the project and handle the documentation for approval by the Animal Experimentation Ethics Committee (CEEA), by the Animal Experimentation Authorization Committee and by the Regional Government.
  • Custom in vivo studies, different administration routes (intravenous - tail vein and retro-orbital sinus administration - oral, intra-peritoneal, subcutaneous and intramuscular), dosing regimen and readouts on demand
  • Various administration routes: intravenous (tail vein and retro-orbital sinus administration) oral, intra-peritoneal, subcutaneous and intramuscular
  • The dosing regimen and sampling are designed according to the project needs and prior information available on the study compounds
  • Metabolite identification and profiling in vivo
  • Analysis of different matrices: blood, plasma, cerebrospinal fluid, tissues, bile, urine and feces.
  • Solid state evaluation and enhanced formulation for problematic compounds
  • Biomarker development and application within projects
  • Support of pharmacodynamic and efficacy study design
  • The relationship between concentration-time and response-time profiles varies with different targets and the position of a target in a biological pathway. The team provides analysis and interpretation of pharmacokinetic/pharmacodynamic (PKPD) relationships in support of PD.
  • Analysis of biomarkers can also be conducted at MEDINA, as it can greatly enhance the process; integration of such information in static or ideally dynamic models form the foundation for drug discovery and safety risk assessment.
  • Calculation of Pharmacokinetics parameters:
    • Half-life
    • Cmax
    • Area under curve, AUC
    • Bioavailability
    • Compartment
    • Volume of distribution, Vd
    • Clearance
    • Steady state concentration, CSS
  • Various administration routes: intravenous (tail vein and retro-orbital sinus administration) oral, intra-peritoneal, subcutaneous and intramuscular
  • Evaluation of body weights, clinical signs of toxicity and macroscopic organ toxicity
  • Acute toxicity (non-GLP, OECD Test Guideline 425) for limiting the maximal tolerated dose (MTD)
  • Short-term single dose toxicity for LD50 calculation (non-GLP, OECD Test Guideline 420)
  • Short-term repeated dose toxicity (non-GLP, OECD Test Guideline 407)