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The incentive of these pharmacokinetic DiY blogs was to give colleagues that have an interest in pharmacokinetics and pharmacodynamics a relative simple tool  to use published pk/pd models and make simulations that can be used to deepen the understanding of the tools like TCI that we use in daily practice to perform anaesthesia. We have used the Euler approximation in a spreadsheet and demonstrated that small steps of 5 seconds could be sufficiently closely matched to the exponential equations and graphs that represent the evolution of drug concentrations in a patient. This was possible for bolus, infusion and target controlled infusion in a deterministic way, in other words: based on calculations that are simple and valid for all drugs simulations. For me these spreadsheets are valuable despite the fact that I have developed Tivatrainer(X) that uses analytical equations and is in theory more accurate. For a quick simulation to verify an idea or concept I still use the spreadsheet approach

In part 1 I have explained how a relative simple spreadsheet can produce the concentration of an intravenous drug dose with given pharmacokinetic parameters that describe a 2 or 3 compartment model. In part 2, target controlled infusion(TCI)  for blood control has been introduced together with a method to use two pharmcokinetic models in one simulation: the Eleveld model with and without opioid. In this episode I add the effect compartment and the Emax model for the BIS, available in this  relative new Eleveld population Pk/Pd  model, the first ‘universal’ model for propofol.  The principles on which the spreadsheets are built are  similar for other drugs. So you could use these spreadsheets with a bit of parameter alteration for Lidocaine, Remifentanil, Sufentanil or whatever other drug that can be modelled with compartimental kinetics. In part 1 I have explained how you can verify your simulations with the original study data by what I called the overlaying technique. If your simulation does

In the pharmacokineticsDiY part 1 the numerical approach of pharmacokinetic calculations was explained. Using relative simple formulas implemented in a spreadsheet the concentrations of a drug could be calculated following variable drug input protocols. The Eleveld model for propofol was used. This was not without a reason. Douglas Eleveld and co-authors analyzed the data from numerous other studies, collected in the open Target Controlled In fusion(TCI) initiative, to develop a pharmacokinetic and pharmacodynamic model for broad application in anaesthesia and sedation. Their work is a milestone in the development of Pk/Pd models that will improve the clinical usability of Target Controlled Infusion systems and the understanding and interpretation of the observed effect related to these models.  Until recently most of the implemented models in Target Controlled Infusion systems were limited in usability and hampered by unverified extrapolation of  data from  studies that were not intended to deliver robust, population models for TCI. So a model for an ‘average’ patient could be unreliable

part 1:building and verifying the spreadsheet This blog is about pharmacokinetics: Do It Yourself. Only a bit of knowledge of using spreadsheets is required. If you read publications on pharmacokinetics you will have noticed that the model parameters are usually presented in two different notations: clearances V1,V2,V3,Cl,Cl2,Cl3 and time-constants(V1,k10,k21,k12,k13,k31). For a 3 compartment open model these 6 parameters describe the state of the model. To my knowledge the 2 and 3 compartment models with elimination from the central compartment are currently the only models used in modern infusion pumps that are capable of Target Controlled Infusion. For the clearance annotation the parameters consist of the volumes of the compartments V1, V2, V3 and the clearances (vol/time) to the outside: central clearance Cl and inter-compartmental clearances Cl2 and Cl3 often called Q2 and Q3. For the time constant annotation, it is the volume of the central compartment V1 and the time constants in-between de compartments k12 , k21, k13, k31 (/time)