Aminoglycoside nephrotoxicity: do time and frequency of administration matter?

Beauchamp, Denis; Labrecque, Gaston

doi:10.1097/00075198-200112000-00006

Cited by 60 publications

(22 citation statements)

References 106 publications

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“…The mechanisms associated with temporal variations in AG nephrotoxicity are not completely understood, but two hypotheses can be given. First, temporal variations in PK parameters may be of crucial importance, and second, food intake or the activity period may be of crucial importance (2). The relation between food intake and the interactions of AGs with renal tubular cells seems to be linked to the urine pH (2).…”

Section: Discussionmentioning

confidence: 99%

“…First, temporal variations in PK parameters may be of crucial importance, and second, food intake or the activity period may be of crucial importance (2). The relation between food intake and the interactions of AGs with renal tubular cells seems to be linked to the urine pH (2). The interaction is stronger at low pH than at high pH, since these molecules are fully protonated at low pH.…”

Section: Discussionmentioning

confidence: 99%

“…The interaction is stronger at low pH than at high pH, since these molecules are fully protonated at low pH. It has been shown that the urine pH is higher during the activity period or during the period of food intake and lower during the rest period (2). This could partly explain the lower level of nephrotoxicity during the activity period.…”

Section: Discussionmentioning

confidence: 99%

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Aminoglycoside Nephrotoxicity: Modeling, Simulation, and Control

Rougier

Deroanne

Maurin³

et al. 2003

Antimicrob Agents Chemother

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The main constraints on the administration of aminoglycosides are the risks of nephrotoxicity and ototoxicity, which can lead to acute, renal, vestibular, and auditory toxicities. In the present study we focused on nephrotoxicity. No reliable predictor of nephrotoxicity has been found to date. We have developed a deterministic model which describes the pharmacokinetic behavior of aminoglycosides (with a two-compartment model), the kinetics of aminoglycoside accumulation in the renal cortex, the effects of aminoglycosides on renal cells, the resulting effects on renal function by tubuloglomerular feedback, and the resulting effects on serum creatinine concentrations. The pharmacokinetic parameter values were estimated by use of the NPEM program. The estimated pharmacodynamic parameter values were obtained after minimization of the leastsquares objective function between the measured and the calculated serum creatinine concentrations. A simulation program assessed the influences of the dosage regimens on the occurrence of nephrotoxicity. We have also demonstrated the relevancy of modeling of the circadian rhythm of the renal function. We have shown the ability of the model to fit with 49 observed serum creatinine concentrations for a group of eight patients treated for endocarditis by comparison with 49 calculated serum creatinine concentrations (r 2 ‫؍‬ 0.988; P < 0.001). We have found that for the same daily dose, the nephrotoxicity observed with a thrice-daily administration schedule appears more rapidly, induces a greater decrease in renal function, and is more prolonged than those that occur with less frequent administration schedules (for example, once-daily administration). Moreover, for once-daily administration, we have demonstrated that the time of day of administration can influence the incidence of aminoglycoside nephrotoxicity. The lowest level of nephrotoxicity was observed when aminoglycosides were administered at 1:30 p.m. Clinical application of this model might make it possible to adjust aminoglycoside dosage regimens by taking into account both the efficacies and toxicities of the drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Aminoglycoside Nephrotoxicity: Modeling, Simulation, and Control

Rougier

Deroanne

Maurin³

et al. 2003

Antimicrob Agents Chemother

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“…The nephrotoxicity was 34.6% during periods of resting (midnight to 7:30 a.m.) against 12.5% (8:00 a.m. to 3:30 p.m.) and 9.3% (4:00 p.m. to 11:30 p.m.) during active periods [50]. This variation is related to alterations in urinary pH, as there is greater interaction of aminoglycosides and anionic phospholipids when the pH is low [78]. It was seen, both in animals and humans, that the urinary pH is higher during activity and after eating and lower during rest and low food intake [79].…”

Section: Clinical Trialsmentioning

confidence: 99%

<![CDATA[<B>Aminoglycoside nephrotoxicity</B>]]>

Oliveira¹,

Cipullo²,

Burdmann³

2006

Braz. j. cardiovasc. surg.

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Aminoglycoside are frequently used due to its high efficacy against gram-negative bacteria and positive synergism with other antibiotics against gram-positive organisms. They are commonly used for prevention and treatment of infection complications after cardiothoracic surgery. The principal side effect of this class of antibiotics is nephrotoxicity, which may occur in up to 20% of the exposed patients. Although usually reversible, aminoglycosideinduced renal injury prolongs hospitalization time and increase patients cost. Even more important, the occurrence of nephrotoxicity is associated with higher patient mortality. There are some known risk factors for nephrotoxicity development and some measures that may prevent it. This review will cover the most relevant aspects of this important side effect of aminoglycoside therapy. Descriptors 445OLIVEIRA, JFP ET AL -Aminoglycoside nephrotoxicity Braz J Cardiovasc Surg 2006; 21(4): 444-452

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“…Surprisingly, it has been found that nephrotoxicity varies according to the time of day at which the drug is administered. Administration during active periods (1:30 pm) has been shown to be associated with less nephrotoxicity compared with administration during rest periods (1:30 am) (Beauchamp and Labrecque 2001 ).…”

Section: Toxicodynamicsmentioning

confidence: 99%

Aminoglycosides

Bulik

Nightingale

Nicolau³

2013

Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics

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Aminoglycoside antibiotics, bactericidal agents which irreversibly bind to the 30s ribosomal subunit and cause the inhibition of protein synthesis, have remained a vital aspect of the antimicrobial armamentarium since their introduction over 5 decades ago. Aminoglycosides are broad-spectrum agents with activity against a wide range of aerobic Gram-negative and Gram-positive pathogens, in addition to certain mycobacteria. Due to poor oral absorption, aminoglycosides are mainly administered as parenteral or inhalational agents. They demonstrate low protein binding and distribute freely into the interstitial or extracellular fl uid. These agents are eliminated from the body via glomerular fi ltration with 99% of a dose excreted unchanged in the urine. As such, the aminoglycosides require dose adjustment in the presence of renal dysfunction to avoid drug related toxicities. Understanding of the pharmacokinetic-pharmacodynamic properties of the aminoglycosides has allowed practitioners to utilize these agents with minimization of drug related toxicities. Pharmacodynamically optimized dosing of the aminoglycosides includes the administration of large doses once daily to both minimize the drug toxicities associated with elevated trough levels, and to optimize the postantibiotic eff ects observed with these agents. For patients who are not candidates for high-dose once daily dosing, these patients are administered aminoglycosides via the "traditional method" which involves multiple administrations of smaller doses every 8 hours. Overall, despite some drug related toxicities which can be overcome through the optimization of PK-PD, the aminoglycosides remain a vital component of a practitioner's arsenal against infection.

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Aminoglycoside nephrotoxicity: do time and frequency of administration matter?

Cited by 60 publications

References 106 publications

Aminoglycoside Nephrotoxicity: Modeling, Simulation, and Control

Aminoglycoside Nephrotoxicity: Modeling, Simulation, and Control

<![CDATA[<B>Aminoglycoside nephrotoxicity</B>]]>

Aminoglycosides

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