The main goal of the present study was to investigate the absorption and disposition of levocetirizine dihydrochloride, the R enantiomer of cetirizine dihydrochloride, following a single oral administration (5 mg) of the 14C-labelled compound in healthy volunteers. Configurational stability was also investigated. Levocetirizine was rapidly and extensively absorbed: 85.4% and 12.9% of the radioactive dose were recovered 168 h post-dose in urine and faeces, respectively. Levocetirizine and/or its metabolites were not, or only very poorly, associated with blood cells, as the blood-to-plasma ratio was 0.51 to 0.68. The mean apparent volume of distribution (Vz/F) was 26.9 1 (0.3 l/kg) indicating that the distribution of levocetirizine is restrictive. The protein binding of radiolabelled levocetirizine was 96.1% l h after administration. In vitro, at concentrations ranging from 0.2 microg/ml to 1 microg/ml, the protein binding was 94.8% to 95.0%. Levocetirizine is very poorly metabolised. The cumulative 48-h excretion as parent compound accounted for 85.8% of the oral dose, equivalent to 95% of the total radioactivity excreted at this time. At least 13 minor metabolites were detected in urine and represented 2.4% of the dose at 48 h. The metabolic pathways involved in levocetirizine metabolism are oxidation (hydroxylation, O-dealkylation, N-oxidation and N-dealkylation), glucuroconjugation, taurine conjugation and glutathione conjugation with formation of the mercapturic acids. There was no evidence of chiral inversion of levocetirizine in humans. This result is consistent with that obtained in preclinical studies.

No abstract

No abstract

No abstract

Back-up heaters are essential for sustainable retrofit heat pump systems to achieve low capital costs and high system temperatures. Despite its importance, current literature focuses primarily on single aspects of the interaction between the back-up heater and the heat pump system. Furthermore, influences of varying scenarios are typically not considered. This paper simultaneously investigates the impact of 18 different scenarios on the optimal answer to the questions: Which back-up heater to choose, where to place it, and how to control it? A scenario consists of boundary conditions for weather, building envelope, radiator sizing, operational envelope, and the electricity-to-gas price/emission ratio, respectively. Using annual dynamic Modelica simulations, we evaluate and assess all interdependencies based on a full factorial design. We analyze final energy consumption, thermal comfort, and back-up heater as objectives. For gas-fired back-up heaters, the optimal placement and control align with current state-of-the-art recommendations. However, for electric back-up heaters, current guideline recommendations yield up to 30% higher operational costs and emissions compared to our findings. Consequently, future studies should develop optimal design rules for sustainable retrofit heat pump systems.

No abstract

Towards the analysis and optimization of a coupled building energy sector, various component model libraries for hydraulic, ventilation, electrical, control, and building domains exist. However, no uniform open-source framework to couple these domains in a holistic building energy system simulation exists. Thus, we present BESMod, an open-source Modelica library, providing a modular approach towards domain-coupled building energy system simulations. BESMod relies on existing component specialized model libraries for the underlying physics. For the analysis of complex system simulations, user-friendly parameterization, consistent model interfaces, precalculated KPIs and debugging options are applied. The library is available at www.github.com/RWTH-EBC/BESMod. This paper motivates the library, lays out the interaction with existing model libraries and the general modular approach. An exemplary use case demonstrates the applicability of BESMod. Concluding, we motivate future development options.

No abstract