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Review
. 2023 May 5;15(5):1411.
doi: 10.3390/pharmaceutics15051411.

Systematic Review and Meta-Analysis of the Effect of Loop Diuretics on Antibiotic Pharmacokinetics

David A Kerling  1 , Sarah C Clarke  1 , Jesse P DeLuca  2 , Martin O Evans  2 , Adrian T Kress  2 , Robert J Nadeau  2 , Daniel J Selig  2
Affiliations
Review

Systematic Review and Meta-Analysis of the Effect of Loop Diuretics on Antibiotic Pharmacokinetics

David A Kerling et al. Pharmaceutics. .

Abstract

Loop diuretics and antibiotics are commonly co-prescribed across many clinical care settings. Loop diuretics may alter antibiotic pharmacokinetics (PK) via several potential drug interactions. A systematic review of the literature was performed to investigate the impact of loop diuretics on antibiotic PK. The primary outcome metric was the ratio of means (ROM) of antibiotic PK parameters such as area under the curve (AUC) and volume of distribution (Vd) on and off loop diuretics. Twelve crossover studies were amenable for metanalysis. Coadministration of diuretics was associated with a mean 17% increase in plasma antibiotic AUC (ROM 1.17, 95% CI 1.09-1.25, I2 = 0%) and a mean decrease in antibiotic Vd by 11% (ROM 0.89, 95% CI 0.81-0.97, I2 = 0%). However, the half-life was not significantly different (ROM 1.06, 95% CI 0.99-1.13, I2 = 26%). The remaining 13 observational and population PK studies were heterogeneous in design and population, as well as prone to bias. No large trends were collectively observed in these studies. There is currently not enough evidence to support antibiotic dosing changes based on the presence or absence of loop diuretics alone. Further studies designed and powered to detect the effect of loop diuretics on antibiotic PK are warranted in applicable patient populations.

Keywords: antibiotics; drug interactions; loop diuretics; pharmacokinetics.

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Conflict of interest statement

The authors declare no conflict of interest. Material was reviewed by the Walter Reed Army Institute of Research and Walter Reed National Military Medical Center. There is no objection to its presentation and/or publication. The opinions and assertions expressed in this article are those of the authors and do not reflect the official policy or position of the US Army Medical Department, Department of the Army, DoD, or the US Government.

Figures

Figure 1
Figure 1
Forest plots of effect of loop diuretic on (a) area under the curve (AUC); (b) half-life (T1/2); (c) amount of drug in urine (Ae). Chrysos et al 1 (furosemide dosed 1 h prior to antibiotic) and Chrysos et al 2 (furosemide dosed 3 h prior to antibiotic) refer to two separate study arms within the Chrysos et al. study [3,13,14,15,16,17,18,19,20,21,22,23].
Figure 1
Figure 1
Forest plots of effect of loop diuretic on (a) area under the curve (AUC); (b) half-life (T1/2); (c) amount of drug in urine (Ae). Chrysos et al 1 (furosemide dosed 1 h prior to antibiotic) and Chrysos et al 2 (furosemide dosed 3 h prior to antibiotic) refer to two separate study arms within the Chrysos et al. study [3,13,14,15,16,17,18,19,20,21,22,23].
Figure 2
Figure 2
Forest plots of effect of loop diuretic on (a) volume of distribution (Vd); (b) maximum concentration (Cmax); (c) estimated glomerular filtration rate (eGFR). Chrysos et al 1 (furosemide dosed 1 h prior to antibiotic) and Chrysos et al 2 (furosemide dosed 3 h prior to antibiotic) refer to two separate study arms within the Chrysos et al study [3,13,14,16,17,18,21,22,23].
Figure 2
Figure 2
Forest plots of effect of loop diuretic on (a) volume of distribution (Vd); (b) maximum concentration (Cmax); (c) estimated glomerular filtration rate (eGFR). Chrysos et al 1 (furosemide dosed 1 h prior to antibiotic) and Chrysos et al 2 (furosemide dosed 3 h prior to antibiotic) refer to two separate study arms within the Chrysos et al study [3,13,14,16,17,18,21,22,23].
Figure 3
Figure 3
Risk-of-bias plot for crossover studies [3,13,14,15,16,17,18,19,20,21,22,23].
See this image and copyright information in PMC

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