PK/PD Flashcards
what is PK/PD modelling
data driven analyses based on statistical and mathemetical models.
investigate the relationship between the concentration of a drug (pharmacokinetics, PK) and its pharmacological effect (pharmacodynamics, PD).
what are in silico experiments
experimentations performed by computers
what do PK/PD graphs include
pk: conc. vs time
PD: effect vs conc
pk/pd: effect vs time
what does PK/PD include
experiments that involve conc, effect, time using design, analysis modelling and simulations
what are the benefits of PK/PD studies
- relate in vivo to in vitro data
- translate animal models to humans
- explain variabilities in responses
- aid dose and regimen selection
- identify and increase confidence in biomarkers
- understand time course of response, relationship between dose and response, tolerance and sensitization.
These studies provide valuable information about how drugs interact with the body, how their concentrations change over time, and how these changes relate to the observed therapeutic or toxic effects.
what are the three pillars that improve chances of progressing into phase 3 clinical trials.
- exposure at target site of action
- binding to target
- expression of functional activity.
what does pop-pk focus on
identifying causes of variability in pK within a population group
used to determine optimum safe dosing strategies for sub groups
what causes Pk variability in populations
(extent and rates of ADME)
differences in vd (due to weight or protein binding)
differences in bioavailability and absorption rate
and differences in CL due to renal and hepatic function
what causes Pd variability in populations
(relationship between drug conc and effect)
differences in receptor number, affinity, endogenous substances, effects of disease.
what are some differences between classical and population Pk studies
classical: healthy volunteers, small size, dense 1-6 time points, inter individual variability minimized (main focus is on characterizing the drug’s ADME)
population: non healthy volunteers, large or integrated size, few samples for many patients. ( aim to characterize the PK of a drug in a broader population)
what is the aim of PKPB modelling
physiology based pk modelling describes the PK of pharmaceuticals within different organs and tissues
is a form of mechanistic modelling (aims to stimulate complex mechanisms)
used in DDI interaction studies, pharmacogenetics, PK in special populations, first in human dose predictions,
effect of changes in physiology and biochem on PK
what do PKPB models require
system data on organ perfusion, organ volume, body weight, fat content, enzyme transporter and plasma protein abundance. (physiological and biochemical data)
compound data
pKa Fu MW CLint KM VMAX
what leads to different PK/PD outcomes
process/system noise, assumption that individuals have random fluctuations
stochastic modelling is used where randomness or uncertainty plays a fundamental role
