Therapeutic Drug Monitoring
Non-Steady State

IV Infusion - Linear One Compartment

A 40 yo patient (H.O. 45 Kg) was started on intravenous antibiotic therapy at a dose of 500 mg over 60 minutes, twice a day, at 0700 and 1900 hr. On Day 2, three blood samples were collected and analyzed for drug concentration. These sample were determined to contain 4.7 mg/L (at 0630), 14.2 mg/L (at 0945) and 5.4 mg/L (at 1830).

Day/Time (hhmm) Dose (mg/hr) Sample (mg/L)
Day 1 at 0700 500 over 1 hr  
Day 1 at 1900 500 over 1 hr  
Day 2 at 0630   4.7
Day 2 at 0700 500 over 1 hr  
Day 2 at 0945   14.2
Day 2 at 1830   5.4

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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