One of the major concerns for all in vivo experiments is intra- and inter-subject variability, which can be a great source of inaccuracy. The aim of this study is, therefore, to estimate the ability of parallel vs. cross-over design studies in order to describe the relative pharmacokinetic performance of the studied drug formulations. We analyzed the data from a drug development program that examined the performance of innovative abiraterone acetate formulations against the identical reference product in three stages. In stages 1–3, groups A–F were dosed with the reference product once in a parallel manner. Stage 4 was performed to evaluate the intra-individual variability (IIV) by repeated administration of the reference product to the same animals. Although the geometric mean (90% CI) values of abiraterone AUClast in groups A–F were similar to the IIV group (24.36 (23.79–41.00) vs. 26.29 (20.56–47.00) mg/mL·min·g), the results generated in the isolated parallel groups provided imprecise estimates of the true AUClast values ranging from 9.62 to 44.62 mg/mL·min·g due to chance. Notably, in 4 out of 15 possible pair comparisons between the parallel groups, the confidence intervals did not include 100%, which is the true ratio for all comparisons tested after identical formulation administration to all groups. A cross-over design can significantly improve the methodology in short-term comparative pre-clinical pharmacokinetic studies, and can provide more precise and accurate results in comparison to more traditional pre-clinical study designs.

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Membranes play an important role in the compartmentalization of cells and organs. Up to 500 different lipids have been reported to be present in different biological membranes. The origin and meaning of this diversity is not well understood. Membranes mediate the necessary separation between organizational units, but also provide the possibility to connect them. Overcoming the membrane barriers within the body is a major task for any therapeutic agent. The research of the Wunderli group is concentrated on elucidating the basis of drug–membrane interaction and permeation processes, on unraveling the mechanism of action of multi-substrate membrane transporters such as the multi-drug resistance protein P-glycoprotein (P-gp), and on the modulation of paracellular diffusion. Three major projects are pursued: (1) drug–membrane interaction and permeation studies with liposomes of different lipid composition; (2) studies on the mechanism of action of the P-gp with proteoliposomes; (3) modulation of the tight junctions (TJs) of cell barriers to enhance the paracellular transport of hydrophilic therapeutic entities, e.g. peptides.