Concern is continuously raised about the safety of parabens which are present in most of the cosmetic preparations. In this investigation, methyl-, ethyl-, propyl- and butyl paraben (MP, EP, PP, BP), in a commercial cosmetic lotion, were deposited on human skin fragments, collected after surgical operations. Permeated parabens were determined after their passage through human epidermis-dermis layers, fixed on Franz diffusion cells. Bovine serum albumin (3%) was employed as receptor fluid. Then, parabens were assessed by liquid chromatography. The objective of this research was to determine the permeation of these molecules through human epidermis-dermis layers, and their possible passage to body tissues and/or accumulation in skin layers. Two groups of experiments were performed. In the first experimental group (G1), unique doses of the cosmetic were deposited on skin fragments fixed on Franz cells (n = 6), at time 0 h, followed with different withdrawn times of the receptor fluid at 12, 24 and 36 h. G1 results demonstrated that parabens penetration was influenced by their lipophilicity: more lipophilic the parabens were (BP > PP > EP > MP), less they crossed the skin layers (BP < PP < EP < MP). The second experimental group (G2) was constituted of three equal deposits on each Franz cell (n = 6) at different hour times 0, 12 and 24 h followed with three withdrawn times of the receptor fluid at 12, 24 and 36 h. The G2 results indicated that investigated parabens had significant increasing permeations in skin layers. This situation provokes the accumulation of these molecules which were considered by some authors as the cause of skin toxicities and carcinogenicity.

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The anticancer drug capecitabine and its metabolites [including the active metabolite 5-fluorouracil (5-FU)] display high pharmacokinetic inter-patient variability. Such variability, which may lead to treatment failure or toxicity, could need drug concentration measurement to individualize dosing regimen. However, usual assay methods are often long and fastidious. A simultaneous and cost-effective method was thus developed for the determination of the concentrations of these compounds in human plasma. Compounds were extracted via a classic liquid-liquid extraction. Chromatographic analysis was performed on a C18 reverse phase column with detection by atmosphere pressure chemical ionization LC-MS/MS. Our method allows a good chromatographic separation of the compounds and was fully validated following Food and Drug Administration (FDA) recommendations (good selectivity, no carry-over, linearity of the calibration curves without weighting, deviations from nominal concentrations of standard samples lower than 15%, intra- and inter-assay precision and accuracy lower than 15%). Recovery and stability were also acceptable following the FDA guidelines. A matrix effect impairing the determination of 5-FU was avoided by using a stable isotopic derivative of 5-FU as internal standard. Interestingly, this method allows detection of TetraHydroUridine, an inhibitor of ex vivo degradation of metabolites, which is essential for the stability, the adequate conditioning of blood samples and for good laboratory practice, essential in routine determination. This method seems usable to routinely determine concentrations of capecitabine and its metabolites in blood and may be helpful in further studies aiming at performing therapeutic drug monitoring.

The assessment of paracetamol absorption kinetics is reproducible when the drug is given together with a semi-solid meal in Helicobacter pylori-negative healthy subjects.

Mycophenolate mofetil (MMF) is an immunosuppressive drug used as a prophylactic agent to prevent acute graft-versus-host disease (aGVHD) after hematopoietic stem cell transplantation (HSCT). After reduced-intensity conditioning (RIC) regimen, administration of MMF orally 3 times a day (tid) seems to be more beneficial than twice a day (bid). However, information regarding the pharmacokinetic (PK) parameters of mycophenolic acid (MPA), the active metabolite of MMF, administered in this regimen are very limited. We performed a prospective study in 15 patients for whom 3 sets of sampling were performed: at the beginning of the treatment, after 1 week, and after 1 month. Two consecutive 8-hour sets of sampling were performed at day 0 (D0) and D7. Plasma concentrations of MPA were quantified and areas under the curve for 8hours (AUC(0-8)), and maximal and through concentrations were calculated. The results show that AUC(0-8) increases between the beginning of treatment and the end of the first week, but remains stable thereafter. Moreover, a trend to lower AUC(0-8) was observed for the patients who experienced GVHD > or =2 compared to those patients who did not. The other PK parameters are not associated with pharmacodynamic events. A limited sampling strategy with Bayesian estimators is currently under investigation to confirm these data and the role of D7 AUC(0-8) as a potential target of therapeutic drug monitoring (TDM).