A Novel Aminoglycoside Antibiotic Is Developed That Is Intravenously Administered

A novel aminoglycoside antibiotic is developed that is intravenously administered and excreted unchanged in urine with an elimination half-life of 4 hours.  Two different dosing regimens are tested in a clinical trial: smaller doses given 3 times a day and a higher dose given once a day.  The total administered drug amount per kilogram of body weight per day (mg/kg/day) is the same in both regimens.  Serum drug concentration is monitored in both groups and is shown in the graph below:[Blue: once-daily (extended interval) dosing, Green: multiple-daily dosing, MIC: minimum inhibitory concentration] It is found that both regimens are effective against gram-negative pathogens, with clinical improvement occurring slightly earlier on average with once-daily dosing.  Which of the following best explains the efficacy of once-daily dosing despite the short half-life of this antibiotic?

A) Concentration-dependent killing
B) High therapeutic index
C) Linear dose-response relationship
D) Low threshold dose
E) Time-dependent killing

Correct Answer:

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