A 64-year-old man is evaluated for persistent fever and weakness. He has a history of aortic valve replacement for aortic stenosis. Physical examination reveals a new cardiac murmur with scattered petechiae and splinter hemorrhages seen on his extremities. Echocardiogram shows a vegetation involving one of the aortic valve leaflets, and blood cultures grow enterococci. As part of the patient's treatment, 240 mg of intravenous gentamicin is started. The pharmacy calculates that, in this patient, gentamicin has a volume of distribution of 30 L, a half-life of 4 hours, and demonstrates first-order and one-compartment kinetics. Which of the following is the most likely serum drug concentration just before the next dose 8 hours later?

Question

A 64-year-old man is evaluated for persistent fever and weakness.  He has a history of aortic valve replacement for aortic stenosis.  Physical examination reveals a new cardiac murmur with scattered petechiae and splinter hemorrhages seen on his extremities.  Echocardiogram shows a vegetation involving one of the aortic valve leaflets, and blood cultures grow enterococci.  As part of the patient's treatment, 240 mg of intravenous gentamicin is started.  The pharmacy calculates that, in this patient, gentamicin has a volume of distribution of 30 L, a half-life of 4 hours, and demonstrates first-order and one-compartment kinetics.  Which of the following is the most likely serum drug concentration just before the next dose 8 hours later?

Quizplus · Accepted Answer

Optimal antibiotic therapy often requires monitoring of serum drug concentrations to ensure adequate dosing, which is necessary to achieve therapeutic levels while avoiding toxicity (eg, nephrotoxicity due to aminoglycosides). The highest level (peak) of drug concentration is usually ½ hour after intravenous or 1 hour after intramuscular dosing, whereas the lowest drug concentration (trough) occurs during the last ½ hour before the next dose. The drug concentration (mg/L) can be calculated by dividing the drug dose (mg) by the volume of distribution (V_D). V_D refers to the theoretically required volume (in liters) if the drug were contained completely in the plasma. It can vary depending on how well the drug distributes into tissues; the higher the V_D, the greater the drug binds to the tissues. When drug metabolism occurs via first-order kinetics, the half-life (t_1/2) represents the amount of time required to lower the drug concentration by 50%. In this example, the first dose of the drug is 240 mg, V_D is 30 L, and t_1/2 is 4 hours. The initial drug concentration is the dose (240 mg) divided by the V_D (30 L), which equals 8 mg/L. After the first half-life (4 hours), the drug concentration will decrease by half to 4 mg/L. After the next half-life (4 hours later, or 8 hours after the initial dose), the drug concentration will decrease by half again to 2 mg/L (Choices A, B, C, and E). Educational objective: The half-life (t_1/2) of a drug is the time required to lower its concentration by 50%. The volume of distribution (V_D) refers to how well the drug distributes into tissues compared to plasma; the higher the V_D, the greater the drug distribution into the tissues. The drug concentration (mg/L) is equal to drug dose (mg) divided by V_D (L).

A 64-Year-Old Man Is Evaluated for Persistent Fever and Weakness