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VM 8314 Models (putting the whole thing together) Presented to Information Dr. Jeff Wilcke VM 8314 Models Physiologic Descriptions of what is “ACTUALLY” going on. Measure concentrations is specific fluids Deal with an organ or system Mathematical Useful (hopefully) descriptions of concentrations rising and falling that often have lost “the feel of reality.” Dr. Jeff Wilcke VM 8314 Mathematical models Single dose experiment(s) Blood / plasma samples at intervals Analyze plots and make predictions: What plasma concentrations should you expect from X dose. Combine with physiologic information understanding to predict disease effects, species differences. Dr. Jeff Wilcke VM 8314 Mathematical models Modelers talk about “compartments” Central compartment Roughly equivalent to the “vascular space” Peripheral compartment Normal tissue compartment Deep compartment Tissue compartment with great affinity for the drug. Dr. Jeff Wilcke VM 8314 Compartments The number of compartments is NOT a property of the drug. How many samples? What timing? What physiology? The number of compartments is an experimental result. It only tells me how many processes I might be able to describe. Clinically, one compartment is usually sufficient. Dr. Jeff Wilcke VM 8314 One compartment You cannot, and should not, try to tell how many compartments from this graph. You can only discern one line, this is a one compartment outcome. Dr. Jeff Wilcke VM 8314 Two compartment Dr. Jeff Wilcke VM 8314 It’s in the experimental details… The difference between these two is that more samples are included early in the experiment. This essentially means that you can “see” distribution happening if you look more carefully. “2-compartment” does NOT tell you that the drug went any particular place… Dr. Jeff Wilcke VM 8314 Dose dependent behavior Plasma concentrations are directly proportional to the doses given. Effects are “dose dependent” Dr. Jeff Wilcke VM 8314 Dose dependent behavior SO, I double the dose and the plasma concentrations double (I get what I expect). The pharmacokinetics PREDICT that I when I double the dose the concentrations double so THE PHARMACOKINETICS are dose independent. Dr. Jeff Wilcke VM 8314 Dose dependent behavior If I double the dose and the concentrations triple (or only rise by 50%) then the PHARMACOKINETICS change with the dose. In this case the PHARMACOKINETICS are dose dependent. Dr. Jeff Wilcke