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Side effects of aminoglycosides on the kidney, ear and balance in cystic fibrosis.

Prayle A, Watson A, Fortnum H, Smyth A - Thorax (2010)

Bottom Line: The prognosis of CF has improved, and thus side effects of treatments have become increasingly important.Observational studies suggest that the morbidity from side effects of aminoglycosides is disturbingly common, and that aggressive treatment may lead to more side effects.This review of the current literature on side effects of aminoglycosides considers the pathophysiological mechanisms, epidemiology and risk factors, investigation of side effects and preventative strategies.

View Article: PubMed Central - PubMed

Affiliation: Child Health and Nottingham Respiratory Biomedical Research Unit, University of Nottingham, E Floor East Block, Queen's Medical Centre, Nottingham NG7 2UH, UK.

ABSTRACT
Aminoglycoside antibiotics are a central component of the treatment of pulmonary exacerbations of cystic fibrosis (CF) and slow the decline in lung function which ultimately causes the death of most patients. The prognosis of CF has improved, and thus side effects of treatments have become increasingly important. Observational studies suggest that the morbidity from side effects of aminoglycosides is disturbingly common, and that aggressive treatment may lead to more side effects. This review of the current literature on side effects of aminoglycosides considers the pathophysiological mechanisms, epidemiology and risk factors, investigation of side effects and preventative strategies. Treatments which have shown early promise are identified and areas of future research are discussed.

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Related in: MedlinePlus

Effects of saturable uptake on kidney cortical accumulation in single daily versus three times daily dosing. In three times daily dosing (shown in red), all of the area under the curve (AUC; red shaded area) contributes to the uptake of the aminoglycoside into the kidney cortex. However, above a certain threshold (indicated by the arrow), the receptor-mediated uptake of the aminoglycoside is saturated and serum concentrations above this level do not contribute to the uptake of aminoglycoside into the renal cortex. As this threshold is exceeded in single daily dosing (shown in green), a proportion of the single daily dose AUC does not contribute to renal uptake. Thus, the area below this threshold contributes to renal uptake (the green area in single daily dosing). As the green area is smaller than the red area, the renal uptake in single daily dosing is thought to be lower than with the three times daily dosing regimen.
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fig2: Effects of saturable uptake on kidney cortical accumulation in single daily versus three times daily dosing. In three times daily dosing (shown in red), all of the area under the curve (AUC; red shaded area) contributes to the uptake of the aminoglycoside into the kidney cortex. However, above a certain threshold (indicated by the arrow), the receptor-mediated uptake of the aminoglycoside is saturated and serum concentrations above this level do not contribute to the uptake of aminoglycoside into the renal cortex. As this threshold is exceeded in single daily dosing (shown in green), a proportion of the single daily dose AUC does not contribute to renal uptake. Thus, the area below this threshold contributes to renal uptake (the green area in single daily dosing). As the green area is smaller than the red area, the renal uptake in single daily dosing is thought to be lower than with the three times daily dosing regimen.

Mentions: Manipulation of the dosing regimen provides a cost-effective and simple method of reducing kidney injury. Given the saturable uptake of aminoglycosides, it follows that a single daily dose would be expected to be less nephrotoxic than the same daily dose in three divided doses (see figure 2). The TOPIC study, a large randomised trial of tobramycin for patients with CF, established that there is equal efficacy with a single daily dosing regimen as with a multiple daily dosing regimen,27 a finding confirmed in a subsequent meta-analysis.28 In the paediatric group receiving a single daily dose, the serum creatinine level decreased during the course of treatment compared with a rise in the group receiving three divided doses. In further support of renal safety, in the once daily arm the rise in NAG was 33% less than in the group receiving a three times daily regimen in both adults and children.


Side effects of aminoglycosides on the kidney, ear and balance in cystic fibrosis.

Prayle A, Watson A, Fortnum H, Smyth A - Thorax (2010)

Effects of saturable uptake on kidney cortical accumulation in single daily versus three times daily dosing. In three times daily dosing (shown in red), all of the area under the curve (AUC; red shaded area) contributes to the uptake of the aminoglycoside into the kidney cortex. However, above a certain threshold (indicated by the arrow), the receptor-mediated uptake of the aminoglycoside is saturated and serum concentrations above this level do not contribute to the uptake of aminoglycoside into the renal cortex. As this threshold is exceeded in single daily dosing (shown in green), a proportion of the single daily dose AUC does not contribute to renal uptake. Thus, the area below this threshold contributes to renal uptake (the green area in single daily dosing). As the green area is smaller than the red area, the renal uptake in single daily dosing is thought to be lower than with the three times daily dosing regimen.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2921289&req=5

fig2: Effects of saturable uptake on kidney cortical accumulation in single daily versus three times daily dosing. In three times daily dosing (shown in red), all of the area under the curve (AUC; red shaded area) contributes to the uptake of the aminoglycoside into the kidney cortex. However, above a certain threshold (indicated by the arrow), the receptor-mediated uptake of the aminoglycoside is saturated and serum concentrations above this level do not contribute to the uptake of aminoglycoside into the renal cortex. As this threshold is exceeded in single daily dosing (shown in green), a proportion of the single daily dose AUC does not contribute to renal uptake. Thus, the area below this threshold contributes to renal uptake (the green area in single daily dosing). As the green area is smaller than the red area, the renal uptake in single daily dosing is thought to be lower than with the three times daily dosing regimen.
Mentions: Manipulation of the dosing regimen provides a cost-effective and simple method of reducing kidney injury. Given the saturable uptake of aminoglycosides, it follows that a single daily dose would be expected to be less nephrotoxic than the same daily dose in three divided doses (see figure 2). The TOPIC study, a large randomised trial of tobramycin for patients with CF, established that there is equal efficacy with a single daily dosing regimen as with a multiple daily dosing regimen,27 a finding confirmed in a subsequent meta-analysis.28 In the paediatric group receiving a single daily dose, the serum creatinine level decreased during the course of treatment compared with a rise in the group receiving three divided doses. In further support of renal safety, in the once daily arm the rise in NAG was 33% less than in the group receiving a three times daily regimen in both adults and children.

Bottom Line: The prognosis of CF has improved, and thus side effects of treatments have become increasingly important.Observational studies suggest that the morbidity from side effects of aminoglycosides is disturbingly common, and that aggressive treatment may lead to more side effects.This review of the current literature on side effects of aminoglycosides considers the pathophysiological mechanisms, epidemiology and risk factors, investigation of side effects and preventative strategies.

View Article: PubMed Central - PubMed

Affiliation: Child Health and Nottingham Respiratory Biomedical Research Unit, University of Nottingham, E Floor East Block, Queen's Medical Centre, Nottingham NG7 2UH, UK.

ABSTRACT
Aminoglycoside antibiotics are a central component of the treatment of pulmonary exacerbations of cystic fibrosis (CF) and slow the decline in lung function which ultimately causes the death of most patients. The prognosis of CF has improved, and thus side effects of treatments have become increasingly important. Observational studies suggest that the morbidity from side effects of aminoglycosides is disturbingly common, and that aggressive treatment may lead to more side effects. This review of the current literature on side effects of aminoglycosides considers the pathophysiological mechanisms, epidemiology and risk factors, investigation of side effects and preventative strategies. Treatments which have shown early promise are identified and areas of future research are discussed.

Show MeSH
Related in: MedlinePlus