Kuentz, Martin

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Kuentz
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Martin
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Kuentz, Martin

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2017 - 201912020 - 20211
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Autor:in: Kuentz, Martin × Thema: PBPK modeling ×

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Gerade angezeigt 1 - 2 von 2
  • Vorschaubild
    Publikation
    Current challenges and future perspectives in oral absorption research. An opinion of the UNGAP network
    (Elsevier, 04/2021) Kuentz, Martin; Vinarov, Zahari; Bertil, Abrahamsson; Artursson, Per; Batchelor, Hannah; Berben, Philippe; Bernkop-Schnürch, Andreas; Butler, James; Ceulemans, Jens; Davies, Nigel; Dupont, Didier; Eide Flaten, Goril; Fotaki, Nikoleta; Jannin, Vincent; Keemink, Janneke; Kesisoglou, Filippos; Koziolek, Mirko; Augustijns, Patrick; Griffin, Brendan [in: Advanced Drug Delivery Reviews]
    Although oral drug delivery is the preferred administration route and has been used for centuries, modern drug discovery and development pipelines challenge conventional formulation approaches and highlight the insufficient mechanistic understanding of processes critical to oral drug absorption. This review presents the opinion of UNGAP scientists on four key themes across the oral absorption landscape: (1) specific patient populations, (2) regional differences in the gastrointestinal tract, (3) advanced formulations and (4) food-drug interactions. The differences of oral absorption in pediatric and geriatric populations, the specific issues in colonic absorption, the formulation approaches for poorly water-soluble (small molecules) and poorly permeable (peptides, RNA etc.) drugs, as well as the vast realm of food effects, are some of the topics discussed in detail. The identified controversies and gaps in the current understanding of gastrointestinal absorption-related processes are used to create a roadmap for the future of oral drug absorption research.
    01A - Beitrag in wissenschaftlicher Zeitschrift
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    Publikation
    Investigating oral absorption of carbamazepine in paediatric populations
    (2017) Kohlmann, Philip; Stillhart, Cordula; Parrot, Neil; Kuentz, Martin [in: The AAPS Journal]
    Prediction of the pharmacokinetics of orally administered drugs in children is of importance to optimize the efficacy and safety of pediatric medicines. Physiologically based pharmacokinetic (PBPK) models can be helpful for this purpose. However, application of these tools is limited by significant knowledge gaps regarding the physiological and anatomical changes which occur with age. This study aimed at investigating the age-dependent differences in oral absorption of a poorly soluble model compound, carbamazepine (CBZ) in children, infants, and neonates. We developed an oral absorption model in GastroPlus® and, after evaluation of the PBPK model for adults, extrapolation to younger ages was verified with clinical data and sensitivity analyses were applied for uncertain model parameters. We found that age-based scaling of physiological parameters, with clearance in particular, was important to obtain adequate simulation results. The sensitivity analysis revealed that CBZ absorption was influenced by solubility, particle radius, and small intestinal transit time depending on the pediatric age group and CBZ dose. However, in vitro dissolution testing using proposed pediatric biorelevant media suggested no major age dependency of dissolution kinetics. Such better understanding of oral absorption in pediatric patients is required to improve the prediction of exposure in children and the confidence in oral biopharmaceutical tools.
    01A - Beitrag in wissenschaftlicher Zeitschrift