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. This increase may be explained either because DEHP is not extracted by the dialyser or because DEHP comes from the dialysis bath due to contact of blood against plasticized pipes. To explain the increasing concentration of DEHP during treatment of renal failure using plasticized tubing, we propose a pharmacokinetic compartmental model in order to fit raw data obtained from dialysed patients and to get the amount of DEHP which enters the body by AUC calculations. Results obtained after HPLC analysis show a high degree of interpatient variability in DEHP retained. This amount can reach a toxicity level because of repetitive dialysis treatments over prolonged periods of time. In the coming years, it seems necessary to reconsider the use of DEHP as a plasticizer in medical devices. Highly unacceptable amounts of DEHP leached during the dialysis session could be easily avoided by careful selection of haemodialysis tubing.

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. Firstly, dealing with a one-compartment model, we get the concentration in the central compartment after a single oral dose and after successive various doses at various times (first order kinetics). Secondly, dealing with a two-compartment model, also for single or successive various doses, the concentration is expressed when absorption and exponential elimination or distribution rate constants are equal. In all cases, the areas under concentration curves and the mean residence time of the drug are calculated even when cancellation of one exponential term occurs. Furthermore, the concentration at steady-state is taken into account.