Download BestDose_Exercises_answers

Workshop Day 2
Best Dose stand alone exercise
Put the PastRx executable in the “bin” directory of BestDose.
Put the patient files (.mb2) in the “Patients” directory of BestDose.
Exercise 1
a. Design an initial dosing regimen of twice daily vancomycin (1h infusion) in a virtual patient
having these characteristics:
- Male
- 25 years old
- 80 kg, 185 cm
- Serum creatinine (stable): 75 µM
- Cmin target = 20 mg/L
BestDose suggests a loading dose of > 5000 mg followed by a maintenance dose about 2800
mg/12h.
A dosage of 3000 mg/12h will achieve a Cmin > 20 mg/L by day 2
b. Design an initial dosing regimen for the same patient for continuous IV vancomycin
By contrast, a dosage of 3000 mg/24h with continuous IV (option 3) will achieve Cmin > 20 mg/L by
day 2
c. Design an initial dosing regimen for continuous IV vancomycin for the same patient but
assuming a serum creatinine of 180 µM
In this case, BestDose suggests approximately 1750 mg over the first 24h, then 1250 mg/24h
as a maintenance dose.
Exercise 2
a.
-
Create and save a patient file for a patients having these data
IV gentamicin
Female patients, 81 years old
55 kg, 162 cm
Creatinine clearance= 42 ml/min
First dose, day 1: 160 mg at 19:35, over 1h
Concentration measurements: 7.4 mg/L at 21:35 day 1; 2.7 mg/L at 8:00 on day 2
Next dose on day 2 at 20:00
In case of bugs, use the GENT1 file for b. and c. questions
b. Then load the patient file and fit gentamicin.mm model to data
c. Design a dosage regimen to hit a target trough of 1 mg/L and a peak of 15 mg/L
A dosage of 240 mg/36h would achieve Cmax about 14.5 mg/L and a Cmin about 0.8 mg/L at
the steady-state. Once daily dosing would result in larger Cmin, > 1 mg/L
Exercise 3
The GENT2 patient file shows the subsequent days of therapy of the patient describe in exercise 2.
The IV route was switched to intramuscular (IM), and several gentamicin concentrations were
measured.
a. What could explain the apparent gentamicin accumulation in this patient?
Decrease in renal function: CCr went from 42 down to 31 ml/min. While this was not
predictable on day 1, it is well fit retrospectively by the model taking into account the history
of renal function.
b. Design a new dosage regimen to hit a target trough of 1 mg/L and a peak of 15 mg/L with IM
gentamicin
Do not forget to select IM instead of IV, then option 1 for calculating the dose interval, and to
increase the upper bound of the dose interval up to 72 or 96h. Targets may be 15 mg/L 0.5h
after the dose for the IM route.
260 mg/72h will achieve both peak and trough goal. Shorter dose intervals lead to Cmin > 1
mg/L
Exercise 4
Load the VANCO1 patient file.
This file shows the past drug therapy of a female patients who received continuous vancomycin and
experienced drug accumulation over the first days of therapy
a. Fit the vancomycin.mm model to data
b. Use the advanced compute option and do a HMM analysis. Set the probability % of original
pop model prior vs new grid to 10%. Compare the fit quality to the previous one
HMM best fits data, especially concentration #2
c. Use the best fitting option and design a dosage regimen of continuous IV vancomycin to get
the patient vancomycin target concentration at 15 mg/L
BestDose suggests to administer about 80 mg over the first 24h, then 400 mg/24h as the
maintenance dose. We may revise as 0 mg (no dose) for the first 24h, then 500 mg/24h. The Css will
be between 17 and 18 mg/L on day 5. This example illustrate the value of the software to manage
overdosing episode, by calculating when the therapy can be resumed, and which dose to choose.