TY - CHAP A1 - Stephan, Mareike Sophia A1 - Barbirz, Stefanie A1 - Robinson, Tom A1 - Yandrapalli, Naresh A1 - Dimova, Rumiana T1 - Bacterial mimetic systems for studying bacterial inactivation and infection BT - Meeting abstract: 65th Annual Meeting of the Biophysical Society (BPS), Feb. 22-26, 2021 T2 - Biophysical journal : BJ / ed. by the Biophysical Society Y1 - 2021 U6 - https://doi.org/10.1016/j.bpj.2020.11.1087 SN - 0006-3495 SN - 1542-0086 VL - 120 IS - 3 SP - 148A EP - 148A PB - Cell Press CY - Cambridge ER - TY - CHAP A1 - Ramadan, Shahenda A1 - Guerrero, Paula A1 - Nedielkov, Ruslan A1 - Klishin, Nikolai A1 - Dimova, Rumiana A1 - Silva, Daniel V. A1 - Möller, Heiko T1 - Building a mimetic system for unraveling protein-protein interactions on membranes T2 - European biophysics journal : with biophysics letters ; an international journal of biophysics Y1 - 2021 U6 - https://doi.org/10.1007/s00249-021-01558-w SN - 0175-7571 SN - 1432-1017 VL - 50 IS - SUPPL 1 SP - S153 EP - S153 PB - Springer CY - Berlin ; Heidelberg ; New York ER - TY - CHAP A1 - Démaris, Alise A1 - Grišić, Ana-Marija A1 - Huisinga, Wilhelm A1 - Walter, Reinisch A1 - Kloft, Charlotte T1 - Evaluation of dosing strategies of anti-TNF alpha monoclonal antibodies using pharmacokinetic modelling and simulation T2 - Journal of Crohn's and Colitis N2 - Background: Anti-TNFα monoclonal antibodies (mAbs) are a well-established treatment for patients with Crohn’s disease (CD). However, subtherapeutic concentrations of mAbs have been related to a loss of response during the first year of therapy1. Therefore, an appropriate dosing strategy is crucial to prevent the underexposure of mAbs for those patients. The aim of our study was to assess the impact of different dosing strategies (fixed dose or body size descriptor adapted) on drug exposure and the target concentration attainment for two different anti-TNFα mAbs: infliximab (IFX, body weight (BW)-based dosing) and certolizumab pegol (CZP, fixed dosing). For this purpose, a comprehensive pharmacokinetic (PK) simulation study was performed. Methods: A virtual population of 1000 clinically representative CD patients was generated based on the distribution of CD patient characteristics from an in-house clinical database (n = 116). Seven dosing regimens were investigated: fixed dose and per BW, lean BW (LBW), body surface area, height, body mass index and fat-free mass. The individual body size-adjusted doses were calculated from patient generated body size descriptor values. Then, using published PK models for IFX and CZP in CD patients2,3, for each patient, 1000 concentration–time profiles were simulated to consider the typical profile of a specific patient as well as the range of possible individual profiles due to unexplained PK variability across patients. For each dosing strategy, the variability in maximum and minimum mAb concentrations (Cmax and Cmin, respectively), area under the concentration-time curve (AUC) and the per cent of patients reaching target concentration were assessed during maintenance therapy. Results: For IFX and CZP, Cmin showed the highest variability between patients (CV ≈110% and CV ≈80%, respectively) with a similar extent across all dosing strategies. For IFX, the per cent of patients reaching the target (Cmin = 5 µg/ml) was similar across all dosing strategies (~15%). For CZP, the per cent of patients reaching the target average concentration of 17 µg/ml ranged substantially (52–71%), being the highest for LBW-adjusted dosing. Conclusion: By using a PK simulation approach, different dosing regimen of IFX and CZP revealed the highest variability for Cmin, the most commonly used PK parameter guiding treatment decisions, independent upon dosing regimen. Our results demonstrate similar target attainment with fixed dosing of IFX compared with currently recommended BW-based dosing. For CZP, the current fixed dosing strategy leads to comparable percentage of patients reaching target as the best performing body size-adjusted dosing (66% vs. 71%, respectively). KW - linical databases KW - crohn's disease KW - regimen KW - monoclonal antibodies KW - body surface area KW - infliximab KW - fat-free mass KW - certolizumab pegol KW - body mass index procedure Y1 - 2020 U6 - https://doi.org/10.1093/ecco-jcc/jjz203.201 SN - 1873-9946 SN - 1876-4479 VL - 14 IS - Supp. 1 SP - S171 EP - S172 PB - Oxford Univ. Press CY - Oxford ER - TY - CHAP A1 - Bogin, Barry A1 - Hermanussen, Michael A1 - Scheffler, Christiane T1 - Fear, violence, inequality and stunting in Guatemala T2 - American journal of human biology : the official journal of the Human Biology Association Y1 - 2021 U6 - https://doi.org/10.1002/ajhb.23593 SN - 1520-6300 VL - 33 PB - Wiley Interscience CY - New York, NY [u.a.] ER - TY - CHAP A1 - Dunsing, Valentin A1 - Petrich, Annett A1 - Chiantia, Salvatore T1 - Spectral detection enables multi-color fluorescence fluctuation spectroscopy studies in living cells BT - Meeting abstract: 65th Annual Meeting of the Biophysical Society (BPS), Feb. 22-26, 2021 T2 - Biophysical journal : BJ / ed. by the Biophysical Society Y1 - 2021 U6 - https://doi.org/10.1016/j.bpj.2020.11.2206 SN - 0006-3495 SN - 1542-0086 VL - 120 IS - 3, Suppl. 1 SP - 356A EP - 356A PB - Cell Press CY - Cambridge ER -