Initiating and managing therapy - TDM - Modelling
19 important questions on Initiating and managing therapy - TDM - Modelling
What is the pharmacokinetic modeling?
What are the formulas that are used in the 1-compartment model?
2) Cl = K*V
dA/dt = -Cl*C (dA/dt = the rate of change of amount in the body.
or
dA/dt = -k * A
What is the difference between an analytical solution and a numerical solution?
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Which formulas belong to the analytical solution?
C0 = Dose/ V
What are the formulas that belong to a 2-compartment model?
2) k10 = CL/V1
3) k12 = Cl12/V1
4) k21 = Cl21/V2
So, what is the numerical solution?
What are some (dis)advantages of the numerical method?
disadvantages: 1) approximate solution (improved by advanced integration methods), 2) slower execution
What are integration methods for the numerical solution?
- (4th order) Runge-Kutta
- predictor-corrector methods
- Bulirsch-Stoer
What is the critical factor for the numerical solution?
An automated step size control can be the solution or an estimate of error (determined by order).
So, what is data modelling?
You need to determine the best fitting model.
What is nonlinear regression analysis?
Given n observations (with measurement errors)
Given a (PK) model with m (unknown) parameters
To be estimated: best fitting set of parameters.
You generate also a set of data with e.g. Monte Carlo simulation.
What will be the solution with the nonlinear regression analysis?
2) General solution by nonlinear regression analysis: Approximate solution by an iterative algorithm
What are ordinary least squares (OLS)?
What are sources of residual error?
- model misspecification
- errors in timing, dosing, sampling etc.
What is the maximum likelihood (ML)?
What is the objective function value (OFV)?
What is the weighted least squares (WLS)?
What are the criteria for minimization algorithms?
- speed of convergence
What is the difference between global minimum and local minima?
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