Redefining
Pharmacokinetics
Revolutionizing drug and generics development. Estimating a lower boundary of absolute bioavailability from oral data exclusively. Constructing an in vitro system for predicting oral drug absorption.

Early Drug Development

We do not follow the classical development based on bottom-up PBPK models (see rationale & PBFTPK models — PubMed). We perform an oral study with a small number of volunteers and analyze data with the FTPK Software, obtaining the detailed PK profile: number of drug input stages, their duration and input rates, and elimination/disposition rate constants. Most importantly, we estimate — uniquely from an oral study alone — a lower boundary of absolute bioavailability, L_AB; for the simplest case, a one-compartment model with one input stage,

where k_el and τ are the estimates for the elimination rate constant and the duration of drug absorption, respectively, derived from the fitting of the PBFTPK model to the C,t data using the FTPK software.

Phase I–III Clinical Studies

We provide model-informed design and analysis of Phase I, II, and III clinical studies using the FTPK software platform. In addition, we conduct population pharmacokinetic (PopPK) analyses using the PBFTPK models embedded in the FTPK software. The optimization work is facilitated since the L_AB and F/V_d estimates bracket the true volume of distribution:

Besides, population analysis free of the wrong estimates of the absorption rate constant is accomplished.

Development of Generics

Prior to any in vitro study for the development of a generic formulation, we analyze the in vivo data of the Reference formulation using the FTPK software. We then construct the % Absorbed versus time curve following our novel methodology. We then follow our revised IVIVC strategy based on dissolution results of the reference formulation carried out under sink conditions (e.g. USP 4). This approach reveals the IVIVs, if any, for the Reference formulation and guides the rational development of the generic formulation. Our approach aligns with the latest EMA/FDA guidance and F.A.T.-informed science.

Assessment of Generics: Bioequivalence Studies

Prior to the study, innovator and generic products are examined in the spirit delineated in the "Development of Generics" section. Rigorous BE studies are performed to deliver accurate, FDA and EMA regulatory-compliant assessments. Apart from the classical BE report, we provide an additional analysis based on a F.A.T. model-dependent methodology using meaningful parameters, (FD/V_d) and (FD/τV_d), for the extent and rate of absorption for both formulations. In addition, the lower boundary of absolute bioavailability L_AB will be provided for both formulations. Needless to say, we re-analyze failed BE studies using the FTPK software.

Pharmacokinetics: FTPK Software — Population PK: NONMEM

We utilize FTPK software for the analysis of pharmacokinetic data. Six PBFTPK models are currently employed, comprising one- and two-compartment disposition models with one, two, or three input stages. In all cases, the number of input stages is determined, and parameter estimates — along with their associated uncertainties — are obtained for the duration and input rates of each stage, as well as for the elimination rate constant or disposition constants. Most importantly, an estimate of the concentration corresponding to the fraction of dose absorbed is derived, allowing the estimation of a lower bound of absolute bioavailability based solely on oral data, through comparison with the observed maximum concentration.

We conduct population pharmacokinetic (PK) analysis using NONMEM. Population analysis is also applied using FractaLPK, a novel platform developed by Carlos A. Pérez Aparicio (F.A.T. Laboratories, Population Modeling Director). This platform integrates fractional calculus with population PK methodologies, enabling advanced characterisation of drug kinetics. FractaLPK is built around a proprietary high-precision computational engine for evaluating the Mittag-Leffler function (E_α), which allows for the detection and quantification of anomalous (non-Fickian) drug behaviour directly from standard concentration–time data.

Model-Informed, F.A.T.-Based Development of Modified-Release Formulations

The analytical power of FTPK software enhances the rational design of modified-release formulations. This is because sustained-release formulations are typically designed to exhibit an initial immediate-release phase followed by a prolonged sustained-release phase. Consider a company aiming to develop a 20 mg once-daily formulation to replace an existing 10 mg tablet administered twice daily. Analysis of the in vivo published data for the 10 mg tablet using FTPK software can reveal not only the two absorption phases but also the duration of each phase and their corresponding input rates.

Clinical Studies

We perform clinical studies involving human volunteers to explore new ways to diagnose, treat, prevent or understand diseases and health conditions. We carry i) Phase I studies to test safety and dosage, ii) Phase II studies to explore efficacy and side effects in a larger group, iii) Phase III studies to confirm effectiveness and monitor side effects, and iv) Phase IV post-marketing studies to gather additional information on long-term effects. We participate in clinical trials approved in the European Union or Internationally. We collaborate with NKUA's hospitals and private hospitals and local CROs for the registration aspects of the study, monitoring of the patients etc of the clinical trial.

Pharmaceutical Analysis — Organic Synthesis Lab

Analytical characterization of drug substances and products, supporting formulation development and quality assessment for regulatory filings. The analytical work is also extended to identification of drug metabolites using mass spectrometry. The organic synthesis laboratory can carry the synthesis of metabolites. Also, this laboratory utilizes advanced techniques and methodologies to design and execute synthetic routes for a wide range of organic compounds.

Dermopharmaceutics Lab

In a GLP-certified animal laboratory, studies on skin pharmacology, skin toxicity, oxidative stress, antioxidants, and topical preparations are conducted. Examples of studies carried out in the past include the assessment of the healing potential of various compounds, the evaluation of dermatological effects of acute and long-term UV-C exposure, and the in vitro assessment of the effects of portable, domestic UV-C disinfection devices on skin fibroblasts.