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Aminoglycoside pharmacokinetics

What are the pharmacokinetics of aminoglycosides specifically? In this video, Sally Tipping discussed the key parameters.

In this video, educator Sally Tipping poses the question, ‘Is the PK/PD of all aminoglycosides the same?’ and discusses the absorption, distribution, and elimination of aminoglycosides.

While they all exhibit a similar clearance, Vd and t1/2, meaning the same PK model applies, they have different therapeutic ranges in the blood in which they act effectively.

Aminoglycosides are poorly absorbed orally and are administered through various routes, including topically, intrapleurally, intramuscular injections, and incorporation into implant fixations. The video explains the importance of understanding key parameters such as Vd, protein-binding, distribution, and elimination for effective dosing. Special considerations for dosing in different patient groups, such as those with variations in age and renal function and patients with cystic fibrosis, are highlighted. The Cockcroft-Gault equation can be used to inform dosing based on renal function, and mathematical models such as nomograms can predict peaks and troughs in serum concentrations to aid in dosing adjustments. Finally, in the video, the distribution of gentamicin specifically is examined, and its poor distribution into certain sites, such as bone and across membranes, is highlighted.

Once you have watched the video, take a look at more PK vital statistics for gentamicin.

Example PK statistics – gentamicin

  • Bioavailability < 1% after oral or rectal administration. Well absorbed from intramuscular sites (bioavailability 80 – 90%).
  • Peak plasma concentration is seen between 1 – 2 hours when gentamicin is dosed once daily. Mean peak concentrations are lower in neonates than in adults.
  • Effective plasma concentration is 4 – 8 µg/ml. Peak plasma concentrations seen in patients with renal failure are higher; this is because the peak is determined by both the Vd and excretion, which starts as soon as gentamicin is present in the blood.
  • The Vd in an adult is 0.3 L/kg.
  • Vd varies according to age from 0.5 – 0.7 L/kg for a premature newborn to 0.25 L/kg for an adolescent.

In the downloads section below is a document showing estimated penetration levels of gentamicin at different sites.


How does this affect dosing? Let us know your thoughts!

Later this week, you will learn about aminoglycoside dosing regimens, but first, we want to hear your thoughts! As you will learn, aminoglycosides were traditionally administered as multiple doses (usually 2-3) divided across a 24-hour period, however, many organisations have moved to once a day dosing in certain patient groups. Given their short half-life, would you expect them to be effective for the entire 24 hour time period?

Discuss your answer with the other learners in the comments below.

We will return to this question in step 2.7.

When you are ready, move on to the next step, where we will discuss how efficacy is ensured using breakpoints.

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Optimise Aminoglycoside Use in Clinical Practice

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