The line(s) on this graph was calculated from the model shown below.
Figure 16.2.1 Diagram Illustrating Hemodialysis
The value for Clearancehemodialysis depends on the molecular weight of the drug and the fraction unbound, not bound to the plasma protein. The maximum value for Clearancehemodialysis in this simulation was 4 L/hr (67 ml/min) for compounds below 500 Dalton. The value of Clearancehemodialysis for molecules between 500 and 1000 decreased linearly to a value of 0 when the molecular weight is greater than 1000. This value is multiplied by the fraction unbound to give the Clearancehemodialysis value and divided by the apparent volume of distribution to give a rate constant for the hemodialysis process. This is added to kel only during the four hour dialysis period to give a higher effective rate constant.
|Less than or equal to 500 Dalton||fu x 4.0 L/hr|
|500 to 1000 Dalton||L/hr|
|Greater than 1000 Dalton||0.0 L/hr|
Try simulating concentration versus time before, during and after hemodialysis. Look at the effect of protein biding by trying fu values of 0.8, 0.5 and 0.1. The effect of volume of distribution can be studied by trying values of 10, 50 and 100 L. You may need to change the y axis scale to see all the these lines. Finaly try molecular weight values of 125, 750 and 1250 to explore the effect of this drug variable on hemodialysis. Check out the effect of multi-compartment (two compartment) pharmacokinetics by changing k12 to 1.5 and k21 to 1.0 hr-1.
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