Time and Amount of Next Dose

Question: A 45 yr, 74 kg male patient with severe severe infection is started on a new drug. He is given 100 mg as an intravenous bolus. This patient has poor renal function so blood samples were collected at 2 and 12 hours to determine the pharmacokinetics of this drug in this patient. The concentrations were 18.6 and 13.1 mg/L, respectively. If the minimum effective concentration is 10 mg/L calculate the when the next dose should given AND the dose required to increase the concentration back close to the maximum therapeutic concentration or 25 mg/L. HINT: Calculate kel, Cp0, t(10mg/L), V, and next dose.

A dose of 100 mg is given over 1 hour, here assumed to be bolus dose. Time the required for the concentration drop to 10 mg.

Concentration at 2 hour is 18.6 mg/L
Concentration at 12 hour is 13.1 mg/L

First calculate the elimination rate constant.

kel from Cp1 and Cp2

Back calculating to time zero gives the concentration at time zero (immediately after the dose).

Initial concentration after the first dose

We can now calculate the time when the concentration is expected to fall to 10 mg/L.

Time when concentration falls to 10 mg/L

We can now calculate the apparent volume of distribution.

Apparent volume of distribution

The last step is calculate dose required to jump the concentration from 10 mg/L to 25 mg/L. An increase of 15 mg/L.

Next dose

Plot the concentration on the graph by clicking on the 'Plot Line' button.

Investigate the effect of changing the Dose, Dosing interval (tau), elimination rate constant (kel), clearance (CL) and apparent volume of distribution (V) on the plot of plasma concentration (Cp) versus time. Explore the model by changing the parameter(s). Add additional lines with different parameter values using the Plot Line button.

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