Tobramycin exposure from active calcium sulfate bone graft substitute.

Détails

Ressource 1Télécharger: BIB_A0951C3E3C64.P001.pdf (241.60 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_A0951C3E3C64
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Tobramycin exposure from active calcium sulfate bone graft substitute.
Périodique
Bmc Pharmacology and Toxicology
Auteur(s)
Livio F., Wahl P., Csajka C., Gautier E., Buclin T.
ISSN
2050-6511 (Electronic)
ISSN-L
2050-6511
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
15
Numéro
1
Pages
12
Langue
anglais
Notes
Publication types: Clinical Trial ; pdf: Research article
Résumé
BACKGROUND: Bone graft substitute such as calcium sulfate are frequently used as carrier material for local antimicrobial therapy in orthopedic surgery. This study aimed to assess the systemic absorption and disposition of tobramycin in patients treated with a tobramycin-laden bone graft substitute (Osteoset® T).
METHODS: Nine blood samples were taken from 12 patients over 10 days after Osteoset® T surgical implantation. Tobramycin concentration was measured by fluorescence polarization. Population pharmacokinetic analysis was performed using NONMEM to assess the average value and variability (CV) of pharmacokinetic parameters. Bioavailability (F) was assessed by equating clearance (CL) with creatinine clearance (Cockcroft CLCr). Based on the final model, simulations with various doses and renal function levels were performed. (ClinicalTrials.gov number, NCT01938417).
RESULTS: The patients were 52 +/- 20 years old, their mean body weight was 73 +/- 17 kg and their mean CLCr was 119 +/- 55 mL/min. Either 10 g or 20 g Osteoset® T with 4% tobramycin sulfate was implanted in various sites. Concentration profiles remained low and consistent with absorption rate-limited first-order release, while showing important variability. With CL equated to CLCr, mean absorption rate constant (ka) was 0.06 h-1, F was 63% or 32% (CV 74%) for 10 and 20 g Osteoset® T respectively, and volume of distribution (V) was 16.6 L (CV 89%). Simulations predicted sustained high, potentially toxic concentrations with 10 g, 30 g and 50 g Osteoset® T for CLCr values below 10, 20 and 30 mL/min, respectively.
CONCLUSIONS: Osteoset® T does not raise toxicity concerns in subjects without significant renal failure. The risk/benefit ratio might turn unfavorable in case of severe renal failure, even after standard dose implantation.
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/04/2014 16:34
Dernière modification de la notice
20/08/2019 15:06
Données d'usage