.ipred.pred: Absolute population weighted residuals vs population.absval_delta_vs_cov_model_comp: Model comparison plots, of absolute differences in..cov: Absolute value of the conditional weighted residuals vs..pred: Absolute population conditional weighted residuals vs..cov.bw: Absolute conditional weighted residuals vs covariates for.This multidisciplinarity enabled quantification of internal drug exposure-response relationships, contributed to positioning the zebrafish in the preclinical drug development pipeline, and inspired continuous collaborations between experimental and computational scientists. The state-of-the-art methods that we developed included nanoscale blood sampling, sensitive LC-MS/MS methods for drugs and their isomers and metabolites, and three-dimensional microscopy, integrated with non-linear mixed effects modelling to quantify the pharmacological processes in this small vertebrate. In this thesis, we therefore developed and integrated innovative experimental and computational methods for the successful quantification of 1) the internal exposure over time after waterborne drug treatment, 2) disease dynamics and drug-induced changes therein, and 3) between-species differences in disease mechanisms. Translation of pharmacological findings to higher vertebrates requires quantification of the underlying pharmacological and (patho)physiological processes. Show more The zebrafish is a promising vertebrate model organism in early drug discovery and development. This multidisciplinarity enabled quantification of internal drug exposure-response relationships, contributed to. Translational pharmacokinetics-pharmacodynamics in zebrafish: integration of experimental and computational methods Doctoral Thesis The zebrafish is a promising vertebrate model organism in early drug discovery and development. Curriculum Vitae_List of publications_Acknowledgements.
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