## Dosing approaches

### First dose

One approach is to use the population values for phenytoin. With
this method we would use the population values of Vm = 7 mg/kg/day
and Km = 5 mg/L. Aiming at 15 mg/L for with a patient weight of 80 kg, the
equation

**Equation XX-3 Dosing Rate versus Average Cp>**

Probably better to start out low since toxicity is more probable
above 20 mg/L.

### Second dosing regimen

That is after giving a continuous dose regimen to steady state,
measure plasma concentration and adjust dose. For example if after
420 mg/day,
is 20 mg/L then a downward adjustment would be necessary. If we
assume that the Km is close to the average value of 5 mg/L we can
estimate Vm from the equation above

thus a new dose rate can be calculated

approximately 400 mg/day. **Note**: A reduction in dose of 20
mg/day (5 %) is calculated to give a 5 mg/L change (25 %) in . Another approach
can be describe using the 'graph' (nomogram) shown below.

In Figure XX-6, Line A represents Cp^{ss} = 8 mg/L on 300
mg/day (70 kg = 4.3 mg/kg/day). Line B was drawn to achieve a new
Cp^{ss} = 15 mg/L with a dose of 5.2 mg/kg/day (= 364 mg/day)

The graph is used by plotting the line described by the current
Cp^{ss} and R on the graph, marking a point in the middle of
the contour. From that point draw a line to the desired
Cp^{ss}, the value on the vertical axis gives the required
dose rate, R.

**Figure 93, Nomogram for Phenytoin
Dosing**[3]

### Third dosing regimen

If we already have two plasma concentrations after two dose rates
we can solve the equation

using simultaneous equations.

With = 8.0
mg/L and =
27.0 mg/L for R1 = 225 mg/day and R2 = 300 mg/day

225 * Km + 225 * 8 = 8 * Vm (1)

and

300 * Km + 300 * 27 = 27 * Vm (2)

or multiplying (1) x 300

300 * 225 * Km + 300 * 225 * 8 = 300 * 8 * Vm (3)

and multiplying (2) x 225

300 * 225 * Km + 300 * 225 * 27 = 225 * 27 * Vm (4)

subtracting (4) - (3)

300 * 225 * (27 - 8) = (225 * 27 - 300 * 8) * Vm

and

With these Vm and Km values we can now calculate the next dosing
regimen to try.

### Graphical methods

There are a number of graphical methods which have been described
for when you have data from more than two dosing intervals. Basically
these rely on converting the equations mentioned above into a
straight line form which can be plotted to give the Vm and Km as a
function of the intercept and/or slope.

Want more practice with this type of problem!

Homework Set #6 & #7 - 1995
Homework Set #7 - 1997

This page was last modified: 6 November 2002
Copyright 2001 David W.A. Bourne