Evaluation of renal function equations to predict amikacin clearance

ABSTRACT

Objective: To evaluate the predictive performance of eight renal function equations to describe amikacin elimination in a large standard population with a wide range of age.

Methods: Retrospective study of adult hospitalized patients treated with amikacin and monitored in the clinical pharmacokinetics laboratory of a pharmacy service. Renal function was calculated as Cockcroft-Gault with total, adjusted and ideal body weight, MDRD-4, CKD-EPI, rLM, BIS1, and FAS. One compartment model with first-order elimination, including interindividual variability on clearance and volume of distribution and combined residual error model was selected as a base structural model. A pharmaco-statistical analysis was performed following a non-linear mixed effects modeling approach (NONMEM 7.3 software).

Results: 198 patients (61 years [18–93]) and 566 measured amikacin plasma concentrations were included. All the estimated glomerular filtration rate and creatinine clearance equations evaluated described properly the data. The linear relationship between clearance and glomerular filtration rate based on rLM showed a statistically significant improvement in the fit of the data. rLM must be evaluated carefully in renal failure for amikacin dose adjustment.

Conclusions: Revised Lund-Malmö (rLM) and CKD-EPI showed the superior predictive performance of amikacin drug elimination comparing to all the alternative metrics evaluated.

KEYWORDS:

• Amikacin
• aminoglycosides
• eGFR
• glomerular filtration rate
• pharmacokinetics
• renal elimination

Article highlights

• A population pharmacokinetic approach has been used to evaluate eight renal function metrics of amikacin clearance

• rLM values were more reliable than alternative equations in a wide range of age

• rLM provided a better estimation of amikacin clearance than alternative renal function metrics

• Dose-adjustment based on eGFR must be evaluated carefully in kidney failure

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

Miss Eva María Saéz Fernández and Mr Jonás Samuel Pérez-Blanco were the principal researchers of this study and both contribute as first authors. Miss Eva María Saéz Fernández and Mr Jonás Samuel Pérez-Blanco performed the analysis and interpretation of the data. Eva María Sáez Fernández, Jonás Samuel Pérez-Blanco, Ana Martín-Suárez, José M Lanao and M Victoria Calvo have materially participated in the research and in the preparation and revision of this article. All authors approve the current version of the manuscript to be published and agree to be accountable for all aspects of the work.

Supplementary material

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Additional information

Funding

This paper was not funded.