Pharmacokinetics, pulmonary disposition and tolerability of liposomal gentamicin and free gentamicin in foals.

The researchers studied the effectiveness and tolerance of liposomal gentamicin (LG) and free gentamicin (FG) in foals in treating infections caused by the intracellular pathogen Rhodococcus equi. They found that liposomal gentamicin, a version of the drug encased in liposomes for better cellular absorption, had a longer half-life, wider distribution, and higher intracellular concentrations than free gentamicin. Both forms of the drug were tolerated by the foals without significant renal injury.

Experiment Design and Methods

• The researchers carried out an experimental study on two sets of healthy foals. For one experiment, eight foals were given a single intravenous (i.v.) or nebulised dose of LG or FG. This was done in a balanced Latin square design, with a 14-day washout period between treatments. In another experiment, twelve healthy foals were given either LG or FG at 6.6 mg/kg body weight i.v. every 24 hours for seven doses. Key renal health indicators were measured to assess for renal damage.
• Liquid chromatography-tandem mass spectrometry (an analytical chemistry technique) was used to measure the concentrations of gentamicin, the active therapeutic ingredient in these treatments.

Results

• Liposomal gentamicin demonstrated a significantly higher half-life of about 16.3 hours on average, and a greater capacity to distribute throughout the body, compared to free gentamicin.
• Peak gentamicin concentrations in bronchoalveolar cells (cells in the lungs) were significantly higher for LG compared with FG when administered through both i.v. and nebulised methods.
• Liposomal gentamicin was well tolerated by all foals in the study. Indications of renal injury, a potential side effect of this treatment, were practically equivalent between the sets of foals treated with LG and FG.

Conclusions

• The administration of liposomal gentamicin resulted in higher concentrations of the drug within cells compared to free gentamicin.
• Liposomal gentamicin was found to be tolerated well by the foals, indicating it is a potentially safe treatment option.
• The study suggests that liposomal gentamicin deserves further study as a treatment of infections caused by intracellular pathogens such as Rhodococcus equi.