Pharmacokinetics in Drug Discovery
The aim of this current review is to summarize the present status of pharmacokinetics in Drug Discovery. The review is structured into four sections. The first section is a general overview of what we understand by pharmacokinetics and the different LADMET aspects: Liberation, Absorption, Distribution, Metabolism, Excretion, and Toxicity. The second section highlights the different computational or in silico approaches to estimate/predict one or several aspects of the pharmacokinetic profile of a discovery lead compound. The third section discusses the most commonly used in vitro methodologies. The fourth and last section examines the various approaches employed towards the pharmacokinetic …
Kinetic modelling of passive transport and active efflux of a fluoroquinolone across Caco-2 cells using a compartmental approach in NONMEM.
The purpose was to develop a general mathematical model for estimating passive permeability and efflux transport parameters from in vitro cell culture experiments. The procedure is applicable for linear and non-linear transport of drug with time,10 or10% of drug transport, negligible or relevant back flow, and would allow the adequate correction in the case of relevant mass balance problems. A compartmental kinetic approach was used and the transport barriers were described quantitatively in terms of apical and basolateral clearances. The method can be applied when sink conditions are not achieved and it allows the evaluation of the location of the transporter and its binding site. In this …