Pharmacokinetics and Preliminary Toxicological Analysis Laboratory (PPTAL)

Laboratory of Pharmacokinetics and Initial Toxicology Research

Permeability tests in the PAMPA model
Permeability tests in the Caco-2 model (A→B, B→A, determination of the efflux ratio)

Determination of metabolic pathways and the most probable structures of phase I and II metabolites using liver microsomes, liver S9 fraction or primary hepatocytes
Phenotyping of enzyme isoforms involved in phases I and II of metabolism

PK analyses using liver microsomes, liver S9 fraction or primary hepatocytes – determination of t_1/2 and Cl_int parameters

Drug-drug interactions (DDI) – determination of cytochrome P450 isoforms inhibition/activation
Mutagenicity analysis using the Ames test (including mutagenicity of metabolites after incubation with the S9 liver fraction)
Multiparameter cytotoxicity analysis: MTS, LDH and apoptosis assasys, determination of the intracellular ATP level, determination of the ROS level, detection of reactive metabolites in HepG2 cells
Comprehensive cardiotoxicity testing with the RTCA CardioECR System by Agilent dedicated for the analysis of induced pluripotent cardiomyocytes derived from stem cells. The device is recommended for “Comprehensive In Vitro Proarrhythmia Assay” – an innovative screening initiative in the assessment of proarrhythmic activity, recommended by: FDA, EMA, Health and Environmental Sciences Institute, Safety Pharmacology Society, etc.

Preclinical studies of new compounds: bioavailability, linearity, distribution to tissues, binding to blood proteins, search for elimination routes
Identification of metabolites
Pharmacokinetic profile of compounds in new formulations
Assessment of toxicokinetics
Safety tests (GHS safety class; OECD procedure 420)
Determination of MTD
Selection of drug candidates at an early stage of research