Aminoglycoside Half-Life Calculator
Aminoglycoside Half-Life Calculator
Calculate an aminoglycoside elimination half-life from a paired peak and trough, and check the dosing interval against it.
Aminoglycoside Half-Life
Two-level kineticsPeak 8.0 mg/L, trough 0.8 mg/L, 6 hours between samples
Formula
- peak
- peak concentration, mg/L, drawn at least 30 minutes after the end of the infusion
- trough
- trough concentration, mg/L, drawn just before the next dose
- interval
- hours between the two samples
- ke
- the elimination rate constant, per hour
Worked example
Peak 8.0 mg/L, trough 0.8 mg/L, 6 hours between samples
ke = ln(8.0 ÷ 0.8) ÷ 6 = ln(10) ÷ 6 = 2.303 ÷ 6 = 0.384 per hour
half-life = 0.693 ÷ 0.384 = 1.8 hours
A half-life this short is consistent with normal renal elimination
Half-life and dosing interval
| Half-life | Typical implication |
|---|---|
| 2 – 3 hours | Normal — standard extended-interval dosing applies |
| 4 – 8 hours | Prolonged — consider extending the interval or reducing the dose |
| Over 8 hours | Markedly prolonged — significant renal impairment; reassess dosing entirely |
Reading ke, half-life and the extended-interval rule
The elimination rate constant, ke, describes how quickly a drug concentration falls once distribution is complete: it is the natural log of the ratio between two levels divided by the time separating them. Half-life follows directly as 0.693 (the natural log of 2) divided by ke — the time for the concentration to fall by half, and the number clinicians actually use to reason about dosing intervals.
A normal gentamicin or tobramycin half-life in a patient with normal renal function is roughly 2 to 3 hours, and it rises steeply as glomerular filtration falls, because aminoglycosides are cleared almost entirely by the kidney. For extended-interval, once-daily aminoglycoside dosing, the practical rule is to space doses about 8 to 10 half-lives apart. That allows the trough to fall low enough to exploit the post-antibiotic effect and, just as importantly, to limit accumulation in the renal cortex and the inner ear, where aminoglycoside toxicity concentrates.
The calculation is only as good as the timing of the two samples. Both must be drawn after distribution is complete: the peak at least 30 minutes after the end of the infusion, to avoid catching the tail of the distribution phase and overestimating the true peak, and the trough immediately before the next dose. A peak drawn too early, or a trough drawn too late relative to the next dose, will distort the calculated half-life and any dosing decision made from it.
Frequently asked questions
How is the elimination rate constant, ke, calculated?
As the natural log of the ratio of two levels — typically a peak and a trough — divided by the time between them. Half-life is then 0.693 divided by ke.
What is a normal aminoglycoside half-life?
Roughly 2 to 3 hours with normal renal function. It rises steeply as renal function declines, because aminoglycosides are cleared almost entirely by glomerular filtration.
Why does the dosing interval need to be 8-10 half-lives?
So the trough falls low enough to allow the post-antibiotic effect to work and to limit accumulation in the renal cortex and the inner ear, the two sites of aminoglycoside toxicity.
When should the peak sample be drawn?
At least 30 minutes after the end of the infusion, so distribution is complete. A peak drawn earlier catches the distribution phase and overestimates the true peak.
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References
- Nicolau DP et al. Experience with a once-daily aminoglycoside program administered to 2,184 adult patients. Antimicrob Agents Chemother. 1995;39(3):650-655.
- Winter ME. Basic Clinical Pharmacokinetics, 6th ed. Lippincott Williams & Wilkins.