Can Tobramycin Inhalation Be Improved With a Jet Nebulizer?

Abstract

Data on the pharmacokinetics of antibiotics after inhalation are limited. The aim of this pilot study was to assess the pharmacokinetics of tobramycin under optimalized and standardized aerosol circumstances and, furthermore, to be able to consider possible treatment of exacerbations with inhalation therapy. Six patients were studied after inhalation of 600 mg tobramycin. A jet nebulizer loaded with a 10% solution of tobramycin in water was used. The percentage of the dose that was systemically absorbed ranged from 1.0% to 16.6%. The maximum serum levels of tobramycin ranged from 0.77 mg/L to 3.63 mg/L (mean 1.70 +/- 1.01). The pharmacokinetic data were best described by a two-compartment model. Compared to intravenous administration, the long terminal half-life (mean 9.47 h +/- 3.28 h) could be explained by the slow absorption of tobramycin from the site of administration (flip-flop model). Despite standardized aerosol conditions, considerable interpatient variability was observed. However, the relatively low serum levels allow a further increase of the dose.

In vivo animal models for drug delivery across the lung mucosal barrier☆

“…Slow drug absorption may in turn influence the rate of elimination. This situation is known as flip-flop kinetics [136] and has been observed for tobramycin [140] and insulin [26]. Likewise, estimation of the rate of drug absorption from the lungs simply on the basis of Tmax is not recommended, since a short systemic half life can influence the magnitude of Tmax.…”

Mucin Binding Reduces Colistin Antimicrobial Activity

“…This established that high doses of inhaled colistin can be toxic to humans. The actual dose of active colistin delivered by nebulization of colistimethate solution is unknown; however, assuming (i) a conservative 15% of the nominal dose in the nebulizer (nebulized dose is generally 1 to 2 million IU of colistin, equivalent to 80 to 160 mg of colistimethate or 33 to 67 mg of colistin [colistin base activity, the active moiety] [21]) is delivered to the lung (a deposition efficiency of approximately 10% has been found for aerosolized tobramycin [22,23]) and (ii) subsequent 50% conversion to active colistin (for intravenous dosing, only 20% to 25% is converted, due largely to significant renal clearance of colistimethate before conversion [1]; the amount converted in the lung before being absorbed or cleared has not been reported), then this generates an estimate of approximately 8% of the nominal dose in the nebulizer, or 5 to 10 mg of colistin, as the exposure. However, even this exposure would not be predicted to be safely tolerated based on clinical studies of direct inhalation of colistin sulfate.…”

Dry powder inhalation of colistin in cystic fibrosis patients: A single dose pilot study

“…In a previous study on aerosolized tobramycin a deposition efficiency of approximately 10% was found [35,36]. Using an identical nebuliser-compressor combination, the estimated dose of colistin sulphomethate reaching the target area will therefore be approximately 16 mg. Based on a dosing efficiency of colistin sulphomethate in the Twincer ® inhaler of approximately 60% [20], the amount of colistin sulphomethate dry powder to be inhaled would be approximately 25 mg colistin sulphomethate (excluding excipient) to obtain an equivalent dose.…”