Case Study

PHA 5127

Aminoglycosides

Answers provided by

Jeffrey Stark Graduate Student

 

Background

Gentamicin is used to treat a wide variety of infections. However, due to its toxicity, its use must be restricted to the therapy of life-threatening infections and those for which a less toxic antimicrobial agent is ineffective. Gentamicin follows a one-compartment body model with first-order elimination. Protein binding is low for gentamicin (depending on the test performed, binding is reported to be 0-30%). The volume of distribution is in the range of 10-40L and the half-life is around 2 hours (although there may be considerable variation in this parameter). Dosage is normally 1.0 mg/kg every 8 hours for 7-10 days. The therapeutic range is 1-6 mg/L. Gentamicin is commonly administered via short-term infusions. However, for this case study, assume that the infusions are sufficiently short as to allow IV bolus equations to be used for any necessary calculations. (Don’t worry, we’ll see all of the infusion expressions soon enough. Perhaps too soon for many of you, especially the algebraically and exponentially challenged).

 

Patient information

Mr. I.P. Little (the names have been changed to protect the innocent) is a 69 year old black male with a history of diabetes and hypertension. He is being treated with gentamicin for an infection in his lower leg. The infection was the result of a puncture wound which progressed due to poor circulation and immune response. Additional patient information is given below.

height 5’9’’

weight 170 lb

SCr 1.3 mg/100mL

Note: Serum creatinine may also be expressed as 1.3 mg/dL

While the patient is most likely on other medications as well, assume no drug-drug interactions when addressing the following questions.

 

 

Questions

(1) Predict the creatinine clearance of this patient. Is this in the "normal" range? If not, explain and propose a plausible reason for any deviation from the normal value. Of what importance is Clcreat in this case study? Why is the ideal body weight (IBW) used in the calculation rather than the actual weight?

(2) Predict the ke and t1/2 of gentamicin starting with the equation which relates ke to creatinine clearance. Then, calculate these parameters based on the expression Cl=ke*Vd assuming a Vd of, say,15L (which falls within the normal range). Discuss any difference between the two values.

(3) Using the kinetic parameters found in the part of question (2), calculate the peak and trough levels for gentamicin expected from a dose of 70mg every 8 hours. Do this for the first dose and for the steady-state conditions.

(4) Plasma levels were drawn and gentamicin levels determined after the first dose (70mg every 8 hours). The concentrations were 5.8 mg/L and 3.8 mg/L at 0 and 2 hours post infusion, respectively. Using this data, recalculate the ke, t1/2, Vd, and Cl for this patient.

(5) Using the kinetic parameters found in question (4), calculate the steady-state gentamicin concentrations (peak and trough) expected for a dosing regimen of 70mg every 8 hours. Are these levels within the desired therapeutic range? If not, what changes in the dosing regimen would you recommend (keep the dosing interval at 8 hours)?

pdf file for printing answers