Concept and utility of population pharmacokinetic and pharmacokinetic/ pharmacodynamic models in drug development and clinical practice

Abstract

Due to frequent clinical trial failures and consequently fewer new drug approvals, the need for improvement in drug development has, to a certain extent, been met using model-based drug development. Pharmacometrics is a part of pharmacology that quantifies drug behaviour, treatment response and disease progression based on different models (pharmacokinetic - PK, pharmacodynamic - PD, PK/PD models, etc.) and simulations. Regulatory bodies (European Medicines Agency, Food and Drug Administration) encourage the use of modelling and simulations to facilitate decision-making throughout all drug development phases. Moreover, the identification of factors that contribute to variability provides a basis for dose individualisation in routine clinical practice. This review summarises current knowledge regarding the application of pharmacometrics in drug development and clinical practice with emphasis on the population modelling approach.

Usled čestih neuspeha u kliničkim ispitivanjima i posledično manjeg broja odobrenja novih lekova, potreba za poboljšanjem u razvoju lekova je u određenoj meri zadovoljena korišćenjem pristupa razvoja lekova zasnovanog na modelu. Farmakometrija predstavlja granu farmakologije koja kvantifikuje ponašanje leka, odgovor na terapiju i napredovanje bolesti na osnovu različitih modela (farmakokinetički - FK, farmakodinamički - FD, FK/FD modeli itd.) i simulacija. Regulatorna tela (Evropska agencija za lekove, Uprava za hranu i lekove) podstiču primenu modelovanja i simulacija u svrhu lakšeg donošenja odluka tokom svih faza razvoja lekova. Štaviše, identifikacija faktora koji doprinose varijabilnosti predstavlja osnovu za individualizaciju doze u rutinskoj kliničkoj praksi. Ovaj revijalni rad sumira trenutno znanje u vezi sa primenom farmakometrije u razvoju lekova i kliničkoj praksi sa fokusom na populacionu analizu.