Determine Parameters from Post IV Infusion Data

IV Infusion - Linear One Compartment

A drug was administered by IV infusion of 15 mg/hr for 45 min to healthy volunteer. Seven blood samples were collected at 2, 3, 4, 6, 8, 10, and 12 hours after the start of the infusion. Plasma was separated from each blood sample and analyzed for drug concentration. The collected data are shown in the table below.

Time (hr) Cp (mg/L)
2 0.247
3 0.213
4 0.186
6 0.142
8 0.108
10 0.08
12 0.06

Estimate kel, t1/2, V, and Cl.

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The data above were calculated using the equations:

Cp versus time after an IV infusion - CL

Equation 15.3.1 Drug concentration, Cp, after an IV infusion

The table above provides a set of data for you to analyze. Using these data you should be able to estimate the elimination rate constant (kel), the elimination half-life (t1/2), the apparent volume of distribution (V) and the total body clearance (CL) for the drug. First graph the data on semi-log graph paper and put a straight line thorugh the data. A best fit line. Don't try to put the line through any particular point but through all the data. The best fit line may not go through any of the points. A clear ruler helps. Then you can see the points above and below the line to get a good balance. Draw the line. Estimate the intercept on the left and right extreme of the line. Use these extreme points from the line to estimate kel from the -slope (using the natural log, ln, version) as:

kel from the semi-log slope equation

Now you can either pick one of the concentrations (from the line) and substitute into the equation above to find V. Alternately you could extrapolate the 'best-fit' line back to the end of the infusion, not the y-axis (time zero).

Cp(D) equation after an IV Infusion

Equation 15.3.2 CpD at the end of the infusion period, T

With an estimate of CpD it is possible to rearrange Equation 15.3.2 and calculate V, the apparent volume of distribution:

V from the Cp after IV infusion equation

Equation 15.3.3 V estimated from CpD data

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