Aminoglycoside Kinetics Answers

This section presents a series of questions over material you have studied in the aminoglycoside tutorials. Each question will be asked with a series of answers.

Question #1
The clearance of aminoglycosides:
A. Can be calculated by multiplying the elimination rate constant by the distribution volume.
B. Is often expressed in units of ml/min.
C. Can be thought of as the volume of serum which is cleared of drug in a given period of time.
D. All of the above

Question #2
Given the equation:

Cp = Cpo x e(-Kdt)

What does the term e(-Kdt) represent?
A. The fraction of the serum concentration that is eliminated.
B. The fraction of the serum concentration that remains
C. The fraction of the dose that remains after time (t).
D. The natural logarithm of the elimination rate constant.

Question #3
Thinking about the answer you gave above, what would the term 1-e(-Kdt) represent?
A. The fraction of the serum concentration that is eliminated.
B. The fraction of the serum concentration that remains.
C. The fraction of the dose that remains after time (t).
D. The natural logarithm of the elimination rate constant.

Question #4
The elimination half-life for an aminoglycoside is:
A. Expressed as reciprocal units of time, usually hours.
B. Dependent upon the serum concentration.
C. The time in hours for the serum concentration to decrease by one-half.
D. The time in hours for the serum concentration to increase by one half.

Question #5
C.N. is a 27 year old woman who weighs 60 kg. Laboratory values include BUN = 20 mg/dl and serum creatinine = 1.4 mg/dl. She is to be started on gentamicin. One method to estimate this patient's half life is:
A. Estimate the creatinine clearance--gentamicin clearance will be the same.
B. Assume the half-life is equal to the serum creatinine.
C. Estimate creatinine clearance and use the Dettli equation to estimate gentamicin half-life.
D. Cannot be estimated from the present data.

Question #6
28 year old man weighing 80 kg is brought to the emergency room after a motor vehicle accident. He has multiple injuries including a skull fracture. The physician writes orders for ampicillin, 2g IV q6hr, and tobramycin, 120 mg IV q6hr to cover suspected bacteremia.

Wt=80 kg BUN=40 mg/dl SCr=0.9 mg/dl

The first dose of tobramycin is infused from 0800 to 0900.

Graph the data.

What is the Cpmax?
A. 3.0 ug/ml.
B. 4.6 ug/ml.
C. 3.4 ug/ml.
D. 4.0 ug/ml.

What is this patient's elimination rate constant?
A. 0.365 hours.
B. 0.365/hour.
C. 0.158/hour.
D. 1.9 hours.

Calculate the distribution volume from the graphed data.
A. 15.8 liters.
B. 30.5 liters.
C. 25.1 liters.
D. 20.4 liters.

Is the calculated volume of distribution within expected values.
A. No.
B. Yes.

Determine a dosing regimen for this patient that would provide peaks of approximately 7.0 mg/L and troughs of approximately 1.0 mg/L.
A. 230 mg IV over one hour q6hr.
B. 190 mg IV over one hour q6hr.
C. 230 mg IV over one hour q8hr.
D. 190 mg IV over one hour q12hr.

What parameters should we monitor to aid us in determining need for levels or dosing adjustments?

1. Total body weight
2. Serum creatinine and BUN
3. Liver function tests

A. 1 and 2
B. 2 only
C. 1, 2, and 3
D. None of the above

Question #7
36 year old woman weighing 80 kg was brought to the emergency room after a snowmobile accident. She has a skull fracture and is bleeding internally and now seems to be in acute renal failure. Her last serum creatinine was 5.2 mg/dl. Tobramycin, 80 mg IV q8hrs has been ordered, along with a pharmacokinetic consult.

What is your initial recommendation?

A. Go ahead with the prescribed regimen, renal failure in an acute setting will not affect aminoglycoside kinetics.
B. Consider an alternative antibiotic that is not toxic to the kidneys.
C. Give first dose of 80 mg, then collect three serial levels before giving the second dose.
D. Estimate creatinine clearance using the Cockroft-Gault equation and recommend a dose of 2 mg/kg with a dosing interval based on the Dettli equation. Collect levels at steady state.

Question 8
Accurate assessment of individual half-life requires that serial levels be drawn over what period of time?
A. A minimum of 1.5 times the half-life.
B. A minimum of 1.0 times the half-life.
C. At least 4 hours.
D. Time is not important as long as there is a two-fold difference in serum con

Question #9
Peak and trough gentamicin levels were drawn from a patient on a 100mg IV q6hr regimen. The pharmacist who is analyzing the data realizes that the dose previous to the dose that was studied was given 1 hour late. How does this impact the levels that were drawn?
A. Both the trough and peak will be higher than if the previous dose had been given on time.
B. Both the trough and peak will be lower than if the previous dose had been given on time.
C. The trough will be higher than if the previous dose had been given on time but the peak will not be affected.
D. The trough will be higher and the peak will be lower than if the previous dose had been given on time.

Question #10
What are the goals of pharmacokinetic monitoring of aminoglycosides?
A. Maximize antimicrobial efficacy.
B. Minimize antibiotic toxicity.
C. Both A and B.
D. Neither A nor B.

Question #11
Which of the following factors can influence initial dosing recommendations?
1. Patient age
2. Patient weight
3. Patient gender
4. Concurrent disease states

|A. 1, 2, 3, and 4
B. 1, 2, and 3
C. 1 and 2
D. 2 and 4

Question #12
A 72 year old male cancer patient was begun on vancomycin and tobramycin, 50 mg IV q6hr two days ago for febrile neutropenia following chemotherapy. The physician contacts you now for a pharmacokinetic consult because the patient has not responded to therapy. You call the nursing station and find that a dose has just been infused from 1100 to 1200.

Wt=70 kg Ht=70 inches
BUN=15 mg/dl SCr=1.3 mg/dl

What is this patient's estimated creatinine clearance?
A. 51 ml/min.
B. 76 ml/min.
C. 92 ml/min.
D. 26 ml/min.

Estimate tobramycin elimination rate constant and half-life via the Dettli equation.
A. 0.121/hr; 5.7 hrs.
B. 0.132/hr; 5.2 hrs.
C. 0.154/hr; 4.5 hrs.
D. 0.170/hr; 4.1 hrs.

Based on the half-life that you have estimated, is the prescribed regimen appropriate?
A. Yes, because this patient's situation warrants aggressive therapy.
B. Yes, because the low dose compensates for the short dosing interval.
C. No, because the dose is too high.
D. No, because the dosing interval is inappropriately short and the dose is too low.

You recommended a more reasonable tobramycin regimen and have tailored the regimen based on pharmacokinetic data. One week later, the patient is still febrile and the physician decides to add amphotericin B to the patients regimen. Given that amphotericin B is renally toxic and all patients will exhibit a rise in serum creatinine after several days of therapy, what is your plan?

A. Continue to get trough and peak levels every week for the duration of therapy to ensure patient stays within your desired parameters for troughs and peaks.
B. You have adequately characterized this patient's pharmacokinetics and need do nothing further.
C. You anticipate a decrease in aminoglycoside clearance secondary to administration of amphotericin B, therefore you follow the patient's tobramycin closely, adjusting his regimen appropriately.
D. You tell the physician that amphotericin B cannot be administered concurrently with an aminoglycoside.

This patient is receiving amphotericin B and we expect a change in renal function. He is therefore not at steady state and peak/trough kinetics are inappropriate. Besides stable renal function, what are other determinants of steady state?

1. Doses have been given on a regular schedule, with no missed doses.
2. Patient's condition is stable.
3. Patient's fluid status is stable.

A. 1 and 3.
B. 1,2, and 3.
C. 1 and 2.
D. 1 only.