Advanced in silico modeling explains pharmacokinetics and biodistribution of temoporfin nanocrystals in humans
| Autor: | Mukul Ashtikar, Ge Gao, Volker Albrecht, Laura Jablonka, Annegret Preuß, Fabian Jung, Matthias G. Wacker, Manuela Thurn, Beate Röder, Dietrich Scheglmann |
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| Přispěvatelé: | Publica |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Biodistribution
In silico Pharmaceutical Science Nanoparticle tracking analysis Antineoplastic Agents 02 engineering and technology Temoporfin 03 medical and health sciences chemistry.chemical_compound Pharmacokinetics In vivo Humans Computer Simulation Tissue Distribution Particle Size 030304 developmental biology 0303 health sciences Ethanol Squamous Cell Carcinoma of Head and Neck 021001 nanoscience & nanotechnology Propylene Glycol In vitro Drug Liberation Mesoporphyrins chemistry Head and Neck Neoplasms Delayed-Action Preparations Biophysics Nanoparticles Nanocarriers 0210 nano-technology |
| Popis: | Foscan®, a formulation comprising temoporfin dissolved in a mixture of ethanol and propylene glycol, has been approved in Europe for palliative photodynamic therapy of squamous cell carcinoma of the head and neck. During clinical and preclinical studies it was observed that considering the administration route, the drug presents a rather atypical plasma profile as plasma concentration peaks delayed. Possible explanations, as for example the formation of a drug depot or aggregation after intravenous administration, are discussed in current literature. In the present study an advanced in silico model was developed and evaluated for the detailed description of Foscan® pharmacokinetics. Therefore, in vitro release data obtained from experiments with the dispersion releaser technology investigating dissolution pressures of various release media on the drug as well as in vivo data obtained from a clinical study were included into the in silico models. Furthermore, precipitation experiments were performed in presence of biorelevant media and precipitates were analyzed by nanoparticle tracking analysis. Size analysis and particle fraction were also incorporated in this model and a sensitivity analysis was performed. An optimal description of the in vivo situation based on in vitro release and particle characterization data was achieved, as demonstrated by an absolute average fold error of 1.21. This in vitro-in vivo correlation provides an explanation for the pharmacokinetics of Foscan® in humans. |
| Databáze: | OpenAIRE |
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