Pharmacokinetics, pulmonary disposition and tolerability of liposomal gentamicin and free gentamicin in foals.
Authors: Burton A J, Giguère S, Arnold R D
Journal: Equine veterinary journal
Summary
# Liposomal Gentamicin in Foals: Enhanced Pulmonary Delivery Without Increased Toxicity Gentamicin's poor clinical efficacy against *Rhodococcus equi* in foals stems largely from inadequate intracellular penetration, a limitation that liposomal encapsulation theoretically overcomes by enhancing cellular uptake. Burton and colleagues administered both liposomal gentamicin (LG) and conventional free gentamicin (FG) intravenously and via nebulisation to healthy foals, measuring drug concentrations in plasma, pulmonary epithelial fluid and bronchoalveolar cells using high-resolution liquid chromatography-tandem mass spectrometry. The liposomal formulation demonstrated a substantially longer half-life (16.3 versus 6.2 hours) and larger volume of distribution following i.v. dosing, with critically higher gentamicin concentrations achieved within bronchoalveolar cells after both i.v. (5.27 versus 2.98 mg/l) and nebulised (4.47 versus 1.49 mg/l) administration. Repeated i.v. dosing of LG over seven days produced no greater renal injury than FG, indicating equivalent tolerability despite improved tissue penetration. These findings suggest liposomal gentamicin warrants clinical trials as a superior option for treating intracellular respiratory infections in foals, particularly *R. equi* pneumonia, where delivering adequate drug concentrations within infected cells remains the primary therapeutic challenge.
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Practical Takeaways
- •Liposomal gentamicin may offer superior clinical efficacy for treating Rhodococcus equi infections in foals by achieving higher intracellular drug concentrations than standard gentamicin formulations
- •Liposomal gentamicin appears safe for repeated dosing in foals with no increased nephrotoxicity risk compared to free gentamicin, based on renal injury markers over 7 days of treatment
- •This formulation warrants clinical trials in foals with confirmed R. equi infections to determine if improved drug delivery translates to better treatment outcomes
Key Findings
- •Liposomal gentamicin (LG) had significantly longer half-life (16.3 vs 6.2 hours) and larger volume of distribution (2.00 vs 0.72 l/kg) compared to free gentamicin (FG) after i.v. administration
- •Peak gentamicin concentrations in bronchoalveolar cells were 77% higher for LG vs FG after i.v. administration (5.27 vs 2.98 mg/l) and 200% higher after nebulisation (4.47 vs 1.49 mg/l)
- •Liposomal gentamicin was well tolerated with no significant difference in renal injury markers compared to free gentamicin after 7 repeated doses
- •Encapsulation in liposomes enhances cellular uptake and intracellular drug concentrations, warranting further investigation for treating intracellular pathogens like Rhodococcus equi