Refine
Has Fulltext
- no (46)
Year of publication
Document Type
- Other (46) (remove)
Is part of the Bibliography
- yes (46) (remove)
Keywords
- Absorption kinetics (1)
- Aerosol (1)
- Aluminium (1)
- Aluminium adjuvants (1)
- Haar system (1)
- In vitro dissolution (1)
- Raman lidar (1)
- Toxicokinetic modelling (1)
- inversion (1)
- particle microphysics (1)
Institute
- Institut für Mathematik (46) (remove)
Background: Infliximab (IFX), an anti-TNF monoclonal antibody approved for the treatment of inflammatory bowel disease, is dosed per kg body weight (BW). However, the rationale for body size adjustment has not been unequivocally demonstrated [1], and first attempts to improve IFX therapy have been undertaken [2]. The aim of our study was to assess the impact of different dosing strategies (i.e. body size-adjusted and fixed dosing) on drug exposure and pharmacokinetic (PK) target attainment. For this purpose, a comprehensive simulation study was performed, using patient characteristics (n=116) from an in-house clinical database.
Methods: IFX concentration-time profiles of 1000 virtual, clinically representative patients were generated using a previously published PK model for IFX in patients with Crohn's disease [3]. For each patient 1000 profiles accounting for PK variability were considered. The IFX exposure during maintenance treatment after the following dosing strategies was compared: i) fixed dose, and per ii) BW, iii) lean BW (LBW), iv) body surface area (BSA), v) height (HT), vi) body mass index (BMI) and vii) fat-free mass (FFM)). For each dosing strategy the variability in maximum concentration Cmax, minimum concentration Cmin (= C8weeks) and area under the concentration-time curve (AUC), as well as percent of patients achieving the PK target, Cmin=3 μg/mL [4] were assessed.
Results: For all dosing strategies the variability of Cmin (CV ≈110%) was highest, compared to Cmax and AUC, and was of similar extent regardless of dosing strategy. The proportion of patients reaching the PK target (≈⅓ was approximately equal for all dosing strategies.
We present a project combining lidar, photometer and particle counter data with a regularization software tool for a closure study of aerosol microphysical property retrieval. In a first step only lidar data are used to retrieve the particle size distribution (PSD). Secondly, photometer data are added, which results in a good consistency of the retrieved PSDs. Finally, those retrieved PSDs may be compared with the measured PSD from a particle counter. The data here were taken in Ny Alesund, Svalbard, as an example.
For a singularly perturbed parabolic - ODE system we construct the asymptotic expansion in the small parameter in the case, when the degenerate equation has a double root. Such systems, which are called partly dissipative reaction-diffusion systems, are used to model various natural processes, including the signal transmission along axons, solid combustion and the kinetics of some chemical reactions. It turns out that the algorithm of the construction of the boundary layer functions and the behavior of the solution in the boundary layers essentially differ from that ones in case of a simple root. The multizonal initial and boundary layers behaviour was stated.