Pharmacokinetic profile of once daily intravenous tobramycin in children with cystic fibrosis

Massie, John; Cranswick, Noel

doi:10.1111/j.1440-1754.2006.00944.x

Cited by 34 publications

(22 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, clinical tobramycin dosing, ranging from 8–15 mg/kg/day for cystic fibrosis patients (Massie and Cranswick 2006; Flume et al 2009), is a fraction of the high dose (100 mg/kg/day) used to rapidly induce ototoxicity in the animal model. Although a clinical D-met dose is not yet determined to protect from tobramycin, D-met has demonstrated significant protection from noise-induced hearing loss in animal models with low doses (Clifford et al 2011).…”

Section: Discussionmentioning

confidence: 99%

d -Methionine reduces tobramycin-induced ototoxicity without antimicrobial interference in animal models

Fox

Cooper

Speil

et al. 2016

Journal of Cystic Fibrosis

View full text Add to dashboard Cite

Background Tobramycin is a critical cystic fibrosis treatment however it causes ototoxicity. This study tested D-methionine protection from tobramycin-induced ototoxicity and potential antimicrobial interference. Methods Auditory brainstem responses (ABR) and outer hair cell (OHC) quantifications measured protection in guinea pigs treated with tobramycin and a range of D-methionine doses. In vitro antimicrobial interference studies tested inhibition and post antibiotic effect assays. In vivo antimicrobial interference studies tested normal and neutropenic E. coli murine survival and intraperitoneal lavage bacterial counts. Results D-methionine conferred significant ABR threshold shift reductions. OHC protection was less robust but significant at 20 kHz in the 420 mg/kg/day group. In vitro studies did not detect D-methionine-induced antimicrobial interference. In vivo studies did not detect D-methionine-induced interference in normal or neutropenic mice. Conclusions D-methionine protects from tobramycin-induced ototoxicity without antimicrobial interference. The study results suggest D-met as a potential otoprotectant from clinical tobramycin use in cystic fibrosis patients.

show abstract

Section: Discussionmentioning

confidence: 99%

d -Methionine reduces tobramycin-induced ototoxicity without antimicrobial interference in animal models

Fox

Cooper

Speil

et al. 2016

Journal of Cystic Fibrosis

View full text Add to dashboard Cite

show abstract

“…The pharmacokinetics of aminoglycosides in patients with CF has been evaluated extensively [33][34][35][36][37][38][39][40][41][42][43][44]. The volume of distribution per kg body weight is often increased, and the elimination half-life is decreased [40].…”

Section: Pharmacokineticsmentioning

confidence: 99%

Aminoglycoside therapy against Pseudomonas aeruginosa in cystic fibrosis: A review

Ratjen

Brockhaus

Angyalosi

2009

Journal of Cystic Fibrosis

View full text Add to dashboard Cite

In patients with cystic fibrosis (CF), respiratory infections with the opportunistic bacterial pathogen Pseudomonas aeruginosa have a major impact on morbidity and mortality. Aminoglycosides, especially tobramycin, have been used successfully to combat these infections. Aminoglycoside penetration of bronchial secretions is poor when the antibiotic is administered intravenously. Nebulization allows direct delivery of the drug to the sites of infection within the airways, while avoiding systemic exposure. Published clinical data show that inhaled tobramycin reduces the bacterial load, improves lung function and reduces the number of hospital admissions. Inhaled tobramycin has been used successfully to eradicate P. aeruginosa in patients with early infection. Maintaining clinical benefits requires chronic tobramycin treatment, and the concept of chronic intermittent inhaled treatment (typically, alternating drug and drug-free periods of 28 days) was introduced to minimize the emergence of aminoglycoside resistant P. aeruginosa strains. Other therapeutic advances include the development of different tobramycin formulations and nebulizers that reduce delivery time without compromising efficacy. An optimal treatment regimen for patients with CF with early or intermittent P. aeruginosa infections remains a high priority to maintain long-term lung health.

show abstract

“…Monitoring is necessary not only to achieve therapeutic success, but also to prevent excessive exposure, which has been associated with a higher incidence of adverse events [14]. The various monitoring methods have made the application of the OD approach in clinical cases much easier, and it is the more common practice throughout most countries today [11, 15–17]. However, to our knowledge no appropriate guidelines for the optimal dosing and monitoring of aminoglycosides have been established for CF patients, in particular in the paediatric group, where it is important to eradicate PA as early and intensively as possible to prevent early colonization of resistant forms.…”

Section: Introductionmentioning

confidence: 99%

Target concentration intervention is needed for tobramycin dosing in paediatric patients with cystic fibrosis – a population pharmacokinetic study

Hennig

Norris

Kirkpatrick

2007

Brit J Clinical Pharma

View full text Add to dashboard Cite

What is already known about this subject • Two recent papers have been published which have attempted to build a full population pharmacokinetic model for tobramycin in children with cystic fibrosis. • However, neither study was able to provide any information about between‐subject variability (BSV) and between‐occasion variability (BOV), which is necessary to justify and draw conclusions about the use of target concentration intervention (TCI). • In the publications no simulations were provided to show any new directions or evaluate current therapy. What this study adds • This study provides sound evidence that TCI must be undertaken in this patient group, as the BOV is significantly less than the BSV. • The simulations from this model clearly show that current dosing and monitoring methods will not achieve the necessary targets to maximize the pharmacokinetic–pharmacodynamic relationships of aminoglycosides in this patient group. • The model presented is able to be easily incorporated into Bayesian dose individualization software, e.g. Abbottbase or TCIworks, to achieve dosing targets more accurately. Aim The primary aim was to estimate the population pharmacokinetic parameters of once‐daily intravenous (i.v.) tobramycin in paediatric cystic fibrosis (CF) patients and to investigate the influence of covariates. The second aim was to assess the need for target concentration intervention (TCI) for tobramycin in this patient group. Methods Retrospective demographic, dosing and concentration data were collected from 35 CF patients (21 female, 14 male) aged 0.5–17.8 years, from whom 318 tobramycin plasma concentrations were available. NONMEM was used to estimate the population pharmacokinetics of tobramycin. Simulations were performed using weight‐based dosing with a weight from a covariate distribution model to evaluated current dosing schedules and monitoring practices. Results A two‐compartment model best described the data with population parameter estimates for clearance of central compartment (CL) of 6.37 l h−1 per 70 kg; volume of central compartment (Vc) of 18.7 l per 70 kg; intercompartmental clearance (Q) of 0.393 l h−1; and volume of peripheral compartment (Vper) of 1.32 l. The inclusion of total body weight as covariate reduced the random component of between‐subject variability in CL from 50.1% to 11.7% and in Vc from 62.2% to 11.6%. The between‐occasion variability on CL was estimated in the final model as 6.5%. Simulations show that one dose does not fit all and TCI and dose adjustment are required. Conclusions This study provides the first pharmacokinetic model of once‐daily i.v. tobramycin for the use of target concentration intervention in paediatric CF patients.

show abstract

Pharmacokinetic profile of once daily intravenous tobramycin in children with cystic fibrosis

Cited by 34 publications

References 30 publications

d -Methionine reduces tobramycin-induced ototoxicity without antimicrobial interference in animal models

d -Methionine reduces tobramycin-induced ototoxicity without antimicrobial interference in animal models

Aminoglycoside therapy against Pseudomonas aeruginosa in cystic fibrosis: A review

Target concentration intervention is needed for tobramycin dosing in paediatric patients with cystic fibrosis – a population pharmacokinetic study

Contact Info

Product

Resources

About