| Autor: |
Yamamoto, Y., Valitalo, P.A.J., Huntjens, D.R., Proost, J.H., Vermeulen, A., Krauwinkel, W., Beukers, M.W., Berg, D.J. van den, Hartman, R.J., Wong, Y.C., Danhof, M., Hasselt, J.G.C. van, Lange, E.C.M. de |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Zdroj: |
CPT: Pharmacometrics & Systems Pharmacology, 6(11), 765–777 |
| Popis: |
Drug development targeting the central nervous system (CNS) is challenging due to poor predictability of drug concentrations in various CNS compartments. We developed a generic physiologically based pharmacokinetic (PBPK) model for prediction of drug concentrations in physiologically relevant CNS compartments. System-specific and drug-specific model parameters were derived from literature and in silico predictions. The model was validated using detailed concentration-time profiles from 10 drugs in rat plasma, brain extracellular fluid, 2 cerebrospinal fluid sites, and total brain tissue. These drugs, all small molecules, were selected to cover a wide range of physicochemical properties. The concentration-time profiles for these drugs were adequately predicted across the CNS compartments (symmetric mean absolute percentage error for the model prediction was |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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