BACKGROUND: : Once daily intravenous aminoglycoside dosing (ODD) is widely used to treat acute Pseudomonas aeruginosa exacerbations in patients with cystic fibrosis. Controversy exists as to what is the most appropriate method of therapeutic drug monitoring (TDM) of such therapy with recommendations including trough plasma concentrations of <1 mg/L or <2 mg/L, area under curve (AUC) and various nomograms. This study aimed to compare the exposures to ODD of tobramycin in adults and children with cystic fibrosis using the AUC and trough TDM approaches. METHODS: : Using a mono-exponential software program to calculate AUC from 2 plasma concentrations, AUCs were determined in 22 adults with pre-dose tobramycin concentrations <1 mg/L. The exposure of 5 children with reduced tobramycin clearances was simulated at the usual recommended dose of 10 mg/kg/daily but retaining a trough <1 mg/L. RESULTS: : A tobramycin dose of 10 mg/kg of tobramycin in these patients with normal serum creatinine and a trough concentration <1 mg/L resulted in exposures in excess of those associated with conventional 8-hourly dosing. CONCLUSIONS: : The TDM approach of a trough <1 mg/L, as used with conventional 8-hourly tobramycin dosing, is not relevant to ODD.
BACKGROUND: : Once daily intravenous aminoglycoside dosing (ODD) is widely used to treat acute Pseudomonas aeruginosa exacerbations in patients with cystic fibrosis. Controversy exists as to what is the most appropriate method of therapeutic drug monitoring (TDM) of such therapy with recommendations including trough plasma concentrations of <1 mg/L or <2 mg/L, area under curve (AUC) and various nomograms. This study aimed to compare the exposures to ODD of tobramycin in adults and children with cystic fibrosis using the AUC and trough TDM approaches. METHODS: : Using a mono-exponential software program to calculate AUC from 2 plasma concentrations, AUCs were determined in 22 adults with pre-dose tobramycin concentrations <1 mg/L. The exposure of 5 children with reduced tobramycin clearances was simulated at the usual recommended dose of 10 mg/kg/daily but retaining a trough <1 mg/L. RESULTS: : A tobramycin dose of 10 mg/kg of tobramycin in these patients with normal serum creatinine and a trough concentration <1 mg/L resulted in exposures in excess of those associated with conventional 8-hourly dosing. CONCLUSIONS: : The TDM approach of a trough <1 mg/L, as used with conventional 8-hourly tobramycin dosing, is not relevant to ODD.
Authors: Kevin J Downes; Molly Hayes; Julie C Fitzgerald; Gwendolyn M Pais; Jiajun Liu; Nicole R Zane; Stuart L Goldstein; Marc H Scheetz; Athena F Zuppa Journal: J Antimicrob Chemother Date: 2020-01-01 Impact factor: 5.790
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Authors: Catherine M T Sherwin; Jeffery T Zobell; Chris Stockmann; Bradley E McCrory; Millie Wisdom; David C Young; Jared Olson; Krow Ampofo; Michael G Spigarelli Journal: J Pharmacokinet Pharmacodyn Date: 2014-01-07 Impact factor: 2.745
Authors: Brianna Hemmann; Elizabeth Woods; Tanya Makhlouf; Chris Gillette; Courtney Perry; Mary Subramanian; Holly Hanes Journal: J Pediatr Pharmacol Ther Date: 2022-09-26
Authors: Netzahualcóyotl Arroyo-Currás; Gabriel Ortega; David A Copp; Kyle L Ploense; Zoe A Plaxco; Tod E Kippin; João P Hespanha; Kevin W Plaxco Journal: ACS Pharmacol Transl Sci Date: 2018-10-05