Maxsim2 - Real-time interactive simulations for computer-assisted teaching of pharmacokinetics and pharmacodynamics.
We developed a computer program for use in undergraduate and graduate courses in pharmacology, pharmacokinetics and pharmacodynamics. This program can also be used in environmental and toxicological studies and preclinical simulation, to facilitate communication between modeling pharmacokineticists and project leaders or other decision-makers in the pharmaceutical industry. The program simulates the drug delivery and transport by means of (I) a six-compartment physiological pharmacokinetic flow model, (II) a system of traditional compartment models, or (III) a target-mediated drug disposition system. The program also can be used to simulate instantaneous equilibria between concentration and pharmacodynamic response, or as temporal delays between concentration and response. The latter is done by means of turnover models (indirect response models). Drug absorption, distribution, and elimination are represented by differential equations, which are described by organ and tissue volumes or other volumes of distribution, blood flows, clearance terms, and tissue-to-blood partition coefficients. The user can control and adjust these parameters by means of a slider in real time. By interactively changing the parameter values and simultaneously displaying the resulting concentration-time and/or response-time profiles, users can understand the major mechanisms that govern the disposition or the pharmacological response of the drug in the organism in real time. Schedule dependence is typically seen in clinical practice with a non-linear concentration-response relationship, and is difficult to communicate except via simulations. Here, we sought to illustrate the potential advantages of this approach in teaching pharmacology, pharmacokinetics, and pharmacodynamics to undergraduate pharmacy-, veterinary-, and medical students or to project teams in drug discovery/development.
Department of Biomedical Sciences and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Box 7028, SE-750 07 Uppsala, Sweden.
Johan
J
Gabrielsson
Department of Systems and Data Analysis, Fraunhofer-Chalmers Centre, SE-412 88 Gothenburg, Sweden.
Kristoffer
K
Andersson
Department of Pharmacology, The Sahlgrenska Academy at University of Gothenburg, Box 431, SE-405 30 Göteborg, Sweden.
Gunnar
G
Tobin
Department of Biomedical Sciences and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Box 7028, SE-750 07 Uppsala, Sweden.
Carina
C
Ingvast-Larsson
Department of Systems and Data Analysis, Fraunhofer-Chalmers Centre, SE-412 88 Gothenburg, Sweden. Electronic address: mats.jirstrand@fcc.chalmers.se.
Mats
M
Jirstrand
D000465:Algorithms; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002415:Cats; D019295:Computational Biology; D003198:Computer Simulation; D003199:Computer Systems; D003194:Computer-Assisted Instruction / Q000379:methods* / Q000706:statistics & numerical data; D004285:Dogs; D004333:Drug Administration Routes; D006736:Horses; D006801:Humans; D008954:Models, Biological; D017711:Nonlinear Dynamics; D010599:Pharmacokinetics; D010600:Pharmacology / Q000193:education*; D012984:Software; D013449:Sulfonamides / Q000008:administration & dosage; D013806:Theophylline / Q000493:pharmacokinetics
D013449:Sulfonamides; D013806:Theophylline; C012655:nimesulide
Interaction; Pharmacodynamics; Pharmacokinetics; Pharmacology training; Real time simulations; Visualization