Simplified Estimation of Aminoglycoside Pharmacokinetics in Underweight and Obese Adult Patients

Pai, Manjunath P.; Nafziger, Anne N.; Bertino, Joseph S.

doi:10.1128/aac.00174-11

Cited by 72 publications

(77 citation statements)

References 28 publications

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“…The standard Cockcroft-Gault, MDRD Study and CKD-EPI equations have been compared in the literature for estimating aminoglycoside clearance. [15][16][17][18] Further, some variants of these equations have also been considered. These include using weight descriptors other than total body weight for the Cockcroft-Gault equation and correction for individual body surface area (BSA) for the MDRD Study and CKD-EPI equations.…”

Section: Introductionmentioning

confidence: 99%

The performances of the Cockcroft-Gault, Modification of Diet in Renal Disease Study and Chronic Kidney Disease Epidemiology Collaboration equations in predicting gentamicin clearance

2013

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Background: It is unclear which renal function equation, employing an isotope dilution mass spectrometry (IDMS)-aligned creatinine assay, best predicts gentamicin clearance. Methods: The performances of the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) Study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations for predicting gentamicin clearances were assessed retrospectively in 240 patients treated with gentamicin during 2011-2012, when the local creatinine assay was IDMSaligned. Comparisons were based on the percentage within 30% of gentamicin clearance (P 30 ) and the root-mean-square error (RMSE) of each equation. Gentamicin clearance was calculated from plasma concentrations using a one-compartment model. Results: The Cockcroft-Gault equation and the CKD-EPI equation corrected for individual body surface area (BSA) were associated with the highest P 30 (69% and 67%, respectively) and lowest RMSE (39 and 36 mL/min, respectively) in the 240 patients. Correction for individual BSA improved the performances of the MDRD Study and CKD-EPI equations in patients with body mass indices <18.5 or 530 kg/m 2 . The equations systematically underestimated gentamicin clearance as gentamicin clearance increased, with performance being inferior with gentamicin clearance 590 versus <90 mL/ min. Conclusions: The CKD-EPI equation corrected for individual BSA, and the Cockcroft-Gault equation, provided the best estimates of gentamicin clearance. The CKD-EPI and MDRD Study equations should be corrected for individual BSA at the extremes of body size, if used for guiding gentamicin therapy. The performances of the equations were inferior in patients with higher values of gentamicin clearance.

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Section: Introductionmentioning

confidence: 99%

The performances of the Cockcroft-Gault, Modification of Diet in Renal Disease Study and Chronic Kidney Disease Epidemiology Collaboration equations in predicting gentamicin clearance

2013

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“…Dosing of aminoglycosides is typically based on total body weight. However, the most appropriate alternative body size descriptor for dosing aminoglycosides at the extremes of weight is not known [17].Unfortunately obese subjects are often excluded from clinical trials during the drug development process [18]. Physiological changes associated with obesity can potentially alter the clearance of commonly used drugs [19].…”

Section: Resultsmentioning

confidence: 99%

The problem of low peak concentration of gentamicin in clinical practice

Goboova¹,

Kuželová

Foltánová

2012

Acta Facultatis Pharmaceuticae Universitatis Comenianae

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Aminoglycoside antibiotics have particular importance in the treatment of Gram-negative infections. Toxicity of gentamicin is well-known, but patients often receive insufficient dosage in clinical practice. The purpose of this study was to refer to the problem of insufficient dosages that were confirmed by low peak concentration and to determine relationship between low peak levels and pharmacokinetic parameters, renal function and body weight.We studied 68 patients who were treated with gentamicin for one year (August 2010 -August 2011). Therapeutic drug monitoring (TDM) was applied for all the patients. Gentamicin peak and trough concentrations were measured by the FPIA (Fluorescence Polarization Immunoassay) method with an analyser, AxSYM of ABBOTT company. We divided the patients into 3 groups according to peak and trough levels.Together 13 (19%) patients had high trough concentrations and optimal peak concentrations. Only 6 (9%) patients had optimal trough and peak levels in the first measurement of plasma concentrations. The third group included 49 patients (72%). These patients had optimal trough levels and low peak levels in the first measurement. 34 patients of the third group (28 males, 6 females) had optimal peak levels after adjustment of dosage in the second measurement. 15 patients, only males did not reach optimal peak levels even after adjustment of dosage in the second measurement.The patients with low peak levels of gentamicin are more frequent than patients with toxic adverse effects in clinical practice. Especially, these are the patients with higher value of body weight and following increased pharmacokinetic parameters: creatinine clearance, total volume of distribution, total clearance and elimination rate constant. The clinical pharmacists have to adjust dosage regimens, especially according to Therapeutic drug monitoring (TDM) and clinical experience. The results of the study have confirmed that the clinical pharmacists must adjust dose regimen not only for patients who require reduced doses but more often for patients who require higher doses than are commonly used in clinical practice. These patients are at risk of underdosing of aminoglycoside antibiotics.

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“…D'autre part, la variable « poids » est pré sente dans la formule de Cockcroft. Ceci peut être un avantage au niveau pharmacociné tique car le poids est une estimation du volume de distribution du mé dicament qui intervient né cessairement dans la pharmacociné tique [48]. Ceci pourrait expliquer que la formule de Cockcroft donne de meilleurs ré sultats dans certaines é tudes de pharmacociné tique et soit encore pré fé ré e par certains auteurs [49].…”

Section: L'estimation Du Dfg : Rappels Statistiquesunclassified

“…En effet, il n'existe pas de consensus clair quant au poids qui doit effectivement être utilisé dans la formule de Cockcroft : poids ré el, poids idé al calculé , poids ajusté , poids « maigre » [26]. Des donné es de simulation ont illustré des discordances significatives en termes d'adaptations posologiques selon que l'un ou l'autre de ces « poids » é tait utilisé , par exemple lorsque des populations obè ses, ou à l'inverse dé nutries, sont considé ré es [47,48,[51][52][53][54][55][56][57][58].…”

Section: L'estimation Du Dfg : Rappels Statistiquesunclassified

“…Les é tudes sur la pré diction de la clairance de mé dicaments (le plus souvent les aminoglycosides et la vancomycine) par les diffé rentes é quations sont plus rares et les ré sultats contradictoires [48,51,58,76,[84][85][86][87][88][89]. Enfin, une autre façon d'illustrer les é ventuelles discordances entre les é quations est de reprendre des donné es d'é tudes cliniques observationnelles ou interventionnelles et de vé rifier si les conclusions des dites é tudes resteraient identiques en utilisant l'é quation de Cockcroft (comme cela a é té fait de prime abord dans la plupart des é tudes) ou une autre é quation.…”

Section: Le Choix De La Formule : Que Nous Dit La Litte´rature ?unclassified

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Adaptation posologique des médicaments et fonction rénale : quel(s) estimateur(s) faut-il choisir ?

Delanaye

Flamant

Guerber³

et al. 2016

Néphrologie & Thérapeutique

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Le choix de la formule d'estimation du dé bit de filtration glomé rulaire (DFG) à utiliser pour l'adaptation posologique fait encore dé bat, principalement entre la formule de Cockcroft et les é quations plus ré centes, MDRD (pour Modified Diet in Renal Disease) et CKD-EPI (pour Chronic Kidney Disease Epidemiology). Les arguments mis en avant en faveur de l'utilisation de la formule de Cockcroft sont : qu'elle a é té pré fé rentiellement utilisé e pour dé cider des adaptations posologiques avant la mise sur le marché des mé dicaments, qu'elle permettrait une meilleure pré diction du risque de survenue des effets indé sirables à l'accumulation des mé dicaments, qu'elle permettrait de limiter le surdosage mé dicamenteux chez la personne âgé e. Dans cet article d'opinion, nous discutons les faiblesses de l'argumentaire des partisans du maintien de l'utilisation de la formule de Cockcroft dans le contexte de l'adaptation posologique, ainsi que les limites et le manque de fiabilité de cette formule. Nous soutenons la recommandation de la Haute Autorité de santé (HAS) sur l'utilisation systé matique, en 2015, de l'é quation CKD-EPI pour l'estimation du DFG. Lorsque le DFG est é valué dans le but d'adapter la posologie d'un mé dicament, la dé sindexation de la surface corporelle est pré fé rable. Compte tenu des difficulté s d'estimation du DFG chez la personne âgé e et chez les individus à gabarit hors norme, nous recommandons d'utiliser en priorité dans ces populations, des mé dicaments pour lesquels un suivi pharmacologique est disponible, ou d'avoir recours à une mé thode de ré fé rence de mesure du DFG.ß 2015 Association Socié té de né phrologie. Publié par Elsevier Masson SAS. Tous droits ré servé s.

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Simplified Estimation of Aminoglycoside Pharmacokinetics in Underweight and Obese Adult Patients

Cited by 72 publications

References 28 publications

The performances of the Cockcroft-Gault, Modification of Diet in Renal Disease Study and Chronic Kidney Disease Epidemiology Collaboration equations in predicting gentamicin clearance

The performances of the Cockcroft-Gault, Modification of Diet in Renal Disease Study and Chronic Kidney Disease Epidemiology Collaboration equations in predicting gentamicin clearance

The problem of low peak concentration of gentamicin in clinical practice

Adaptation posologique des médicaments et fonction rénale : quel(s) estimateur(s) faut-il choisir ?

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