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Using physiology-based pharmacokinetic modelling for mechanistic analyses of drug action in disease and special populations

Published on Jul 21, 20141610 Views

Inter-individual variability in clinical endpoints and occurrence of potentially severe adverse effects may hamper drug development at all phases of (pre-)clinical research. A comprehensive understa

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Using physiology-based pharmacokinetic modelling for mechanistic analyses of drug action in disease and special populations00:00
Agenda - 100:40
Definition of PBPK Modelling01:25
The Very Special Populations03:50
Motivation – need for a PBPK model of preterm born children04:16
Preterm born infants show no loss of fat and water during the first days of life…05:19
Preterm born children show a “catch up grow” in the first 2 years. 06:14
Organ growth in preterm born infants06:55
Evaluation of the preterm PBPK model in a population simulation of Amikacin administration07:51
Evaluation of the preterm PBPK model – clinical data from preterms of different gestational age09:00
2nd data set for evaluation of the preterm PBPK model – Paracetamol10:25
2nd Evaluation of the preterm PBPK model – Paracetamol 11:12
Agenda - 211:48
PBPK/ PD Concept for simulations of naked antibody predosing11:53
PBPK Modell can describe target mediated disposition like behavior PK of the ADC13:03
PBPK Modell can describe the decrease of ADC upload after naked anti body pretreatment13:35
PBPK Modell can describe plasma concentrations of ADC with and without predosing14:10
PBPK Modell can inhibition of tumorgrow by ADC with and without predosing14:23
Agenda - 315:16
Model-based risk assessment in pharmaceutical R&D15:28
The risk for Statin induced myopathy seems to be linked to gene function16:13
Validating the predictive power for PK genotypes 17:12
Population simulations18:35
Calculation of a toxicodynamic (TD) marker for statin toxicity 18:56
Population simulations describe distributions of the toxico-dynamic marker for different genotypes19:34
Prediction of clinical incidence rates for the rare CC-subpopulations.20:26
Summary22:21
Thank you23:11