Therapeutic Drug Monitoring
Non-Steady State

IV Infusion - Linear One Compartment

A 50 yo patient (U.J. 93.5 Kg) was started on intravenous antibiotic therapy at a dose of 1100 mg over 60 minutes, twice a day, at 0600 and 1800 hr. On Day 2, three blood samples were collected and analyzed for drug concentration. These sample were determined to contain 13.9 mg/L (at 0515), 30.7 mg/L (at 0845) and 16.2 mg/L (at 1745).

Day/Time (hhmm) Dose (mg/hr) Sample (mg/L)
Day 1 at 0600 1100 over 1 hr  
Day 1 at 1800 1100 over 1 hr  
Day 2 at 0515   13.9
Day 2 at 0600 1100 over 1 hr  
Day 2 at 0845   30.7
Day 2 at 1745   16.2

Calculate the kel, V, Clearance and t1/2 for this drug in this patient.

Hint: Sketch the expected concentration versus time curve for the second day.


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Some Equations:

The elimination rate constant, kel can be calculated using Equation 6.2.1

kel from two time points

Equation 6.2.1 An equation for determining kel from two data points

Remember drug concentration at future times can be determined using Equation 6.2.2.

Concentration at a second time

Equation 6.2.2 Concentration at another time

The concentration due to the next infusion can be calculated from Equation 6.2.3.

Equation 6.2.3 Concentration versus time, post infusion

Rearranging Equation 6.2.2 and 6.2.3 gives us an equation for the apparent volume of distribution, Equation 6.2.4.

Equation 6.2.4 Apparent volume of distribution

Problem by Dr Vincent Dennis, programming by Dr David Bourne.


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