A pharmacokinetic interpretation of increasing concentrations of DEHP in haemodialysed patients.

The degree of exposure to DEHP was assessed in 11 patients with chronic renal failure undergoing maintenance haemodialysis. The amount of DEHP leached from the dialyser during a 4-h dialysis session was estimated by monitoring the DEHP blood concentration using a HPLC method. When a patient undergoes a dialysis treatment, the concentration of di-2-ethylhexyl phthalate (DEHP) in venous blood is increased when the blood crosses through the dialysis apparatus.

Consequence of equal absorption, distribution and/or elimination rate constants.

When fitting experimental data to an open one- or two-compartment model, with first order kinetics, it may happen that no optimized value is obtained for model parameters. Several authors pointed out that this case is especially encountered when absorption and elimination coefficients approach each other in a one-compartment model or when absorption and exponential elimination or distribution rate constants are equal in a two-compartment model. We analyze these situations of equal coefficients here.

A pharmacokinetic model for multiple sites discontinuous gastrointestinal absorption.

Purpose: To build a pharmacokinetic model taking into account a discontinuous absorption along the gut, from n successive sites, a non-absorbing intestinal segment being always in between two successive sites. To solve the mathematical model linked with the pharmacokinetic model to obtain the concentration and contribution of each site to absorption, area under curve and bioavailability.

Methods: Whatever the number n of sites, we obtained the Laplace transform of amounts of drug in each site, then plasma concentration, so that concentration or AUC were expressed analytically.

Concentration at steady-state after periodic and non-uniform administration of drug.

A two-compartment model, with absorption from the gut and elimination from both compartments, is considered in order to express the concentration at any time and at steady-state when a drug is administered repeatedly according to a dosing schedule non-uniformly distributed over a 24-h interval. A time-delay is included to take into account the drug crossing from the gut to the central compartment.

Local identifiability for two and three-compartment pharmacokinetic models with time-lags.

In this paper, we show that time-lags between compartments in a 2 and 3 compartment pharmacokinetic model may be taken into account but that separate identification for model parameters and for time-lags would not be suitable. Furthermore, it may happen that a time-lag model is locally identifiable while the corresponding model without delay is not. For two-compartment delayed models, with only one observation, it is not necessary to have two different inputs contrary to the case without time-lag.