Plasma and Urine Pharmacokinetics of Oral Fosfomycin Tromethamine in Dogs

SIMPLE SUMMARY: Fosfomycin tromethamine, an oral formulation of Fosfomycin, is the most commonly used formulation in humans due to its improved oral bioavailability. However, the information on Fosfomycin tromethamine in dogs is limited. Thus, this study aimed to determine the pharmacokinetic parameters of oral Fosfomycin tromethamine in canine plasma and urine using liquid chromatography tandem mass spectrometry (LC-MS/MS). Six healthy male beagle dogs underwent a three-period three-treatment study: treatment 1 and 2 with single oral Fosfomycin tromethamine at 40 and 80 mg/kg (the total doses with tromethamine salt were 75 and 150 mg/kg, respectively) and treatment 3 with intravenously Fosfomycin disodium at 57 mg/kg (the total dose with disodium salt was 75 mg/kg). The results indicated that, in dogs, oral Fosfomycin as the tromethamine salt was better absorbed into the blood circulation compared to disodium salt as previously reported. The Fosfomycin concentrations in urine were much higher than those in plasma (>100 fold). There were no serious adverse effects except loose stool in some dogs. These results suggest that Fosfomycin tromethamine could serve as a viable substitute for oral antibiotics in bacterial cystitis treatment in dogs with multidrug resistant infections when other antibiotics have failed. ABSTRACT: Fosfomycin is a broad-spectrum, bactericidal antibiotic with low toxicity. It has been used in human medicine and is a promising candidate for treating infections in veterinary medicine. Different Fosfomycin salts exhibit various degrees of bioavailability. Tromethamine salt is the most commonly used oral form due to its improved bioavailability. However, information regarding its use with dogs is limited. Therefore, this study aimed to investigate the pharmacokinetics of oral Fosfomycin tromethamine in canine plasma and urine using liquid chromatography tandem mass spectrometry (LC-MS/MS). Six healthy male beagles underwent a three-period three-treatment study: treatment 1 and 2 with single oral Fosfomycin tromethamine at 40 and 80 mg/kg (the total doses with tromethamine salt were 75 and 150 mg/kg, respectively), and treatment 3 with intravenously Fosfomycin disodium at 57 mg/kg (the total dose with disodium salt was 75 mg/kg). Dogs receiving oral Fosfomycin tromethamine at 75 and 150 mg/kg, maximal drug concentration (Cmax) in plasma produced results of 34.46 ± 12.52 and 66.40 ± 12.64 µg/mL, oral bioavailability (F) was approximately 38 and 45%, while urine Cmax was 4463.07 ± 2208.88 and 8784.93 ± 2303.46 µg/mL, respectively. No serious adverse effects were reported, except loose stool in some dogs. The tremendously high urine Fosfomycin concentrations indicate that oral Fosfomycin tromethamine is suitable as an alternative treatment for bacterial cystitis in dogs.