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Combined Slow and Fast Infusion

Alternately we can give a loading dose by rapid infusion and then give a slower maintenance infusion once the plateau concentration is achieved.

For example, using the previous data

For theophylline, kel = 0.17 hr^-1; V = 25 L; with a required Cp = 14.1 mg/L

If we wish to give a loading infusion over 30 minutes we need to give the infusion at a rate which will produce Cp = 14.1 mg/L at 30 minutes. Therefore:-

Cp^{30 min} = 14.1 mg/L

thus

k0 = 735 mg/hr

Therefore we need to give a dose of 367 mg over 30 minutes to achieve a plasma concentration of 14.1 mg/L at 30 minutes.

It is important to realize what the steady state plasma concentration would be if we didn't turn this fast infusion off.

which would be quite toxic.

Figure 15.5.1 Linear Plot of Cp versus Time showing Combined and Separate Curves for Both Infusions

Click on the figure to view the Java Applet window
Java Applet as a Semi-log Plot

Consequently we would need to ensure that at 30 minutes the rapid infusion rate was slowed from 735 mg/hr to 60 mg/hr. One way to do this is to only provide 367 mg (or 360 mg) in the infusion syringe at first.

The dosing regimen (or controlled sequence of drug administration) to achieve the desired plasma concentration is:-

a) a loading dose by IV infusion of 367 mg/30 minutes followed by

b) a maintenance IV infusion of 60 mg/hr

Javascript Calculators using Equation 15.2.3 and ???

Calculate Cp given fast and slow k0, kel and V at time t