Transcript Document

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