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Tobramycin For Cystic Fibrosis Improves Therapeutic Ratio Compared to Parenteral Aminoglycosides
A DGReview of :"Pharmacokinetics and bioavailability of aerosolized tobramycin in cystic fibrosis(*)"
Chest
07/25/2002
By Mark Greener
Aerosolised tobramycin's high sputum concentrations "significantly" improve the therapeutic ratio compared to parenteral aminoglycosides in patients suffering from cystic fibrosis.
American researchers - the lead author was from Nemours Children's Clinic, Orlando - used data obtained during two randomised, double blind, placebo-controlled studies with identical designs to assess pharmacokinetics of aerosolised tobramycin. During the studies, 258 patients with cystic fibrosis received tobramycin 300 mg twice daily. Patients took aerosolised tobramycin for 28 days and then received no drug for a further 28 days, which constituted a cycle. Patients received three treatment cycles.
The authors estimated that the mean peak concentration of tobramycin in sputum was 1237 microg/g. Around 95 percent of patients attained tobramycin sputum concentrations that were more than 25 times the minimum inhibitory concentration for the Pseudomonas aeruginosa isolates.
An hour following the dose, the mean serum concentration of tobramycin was 0.95 microg/mL. The authors estimated that 11.7 percent of the nominal dose of inhaled tobramycin was systemically bioavailable. The low serum tobramycin concentrations reduced the risk of systemic adverse events. Tobramycin accumulated in neither the sputum nor serum.
The authors found that the pharmacokinetic data followed a two-compartment model. The model was comparable to that following parenteral administration.
The authors commented that aerosolised tobramycin is associated with high sputum concentrations that ensure effective antibiotic levels at the site of the infection. Indeed, the authors add that inhaled tobramycin "significantly" improves the therapeutic ratio compared to parenteral aminoglycosides.
Chest 2002;122:219-26.
"Pharmacokinetics and bioavailability of aerosolized tobramycin in cystic fibrosis(*)"
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