Pharmacokinetics of a single bolus intravenous, intramuscular and subcutaneous dose of disodium fosfomycin in horses.
Pharmacokinetic parameters of fosfomycin were determined in horses after the administration of disodium fosfomycin at 10 mg/kg and 20 mg/kg intravenously (IV), intramuscularly (IM) and subcutaneously (SC) each. Serum concentration at time zero (C(S0)) was 112.21 +/- 1.27 microg/mL and 201.43 +/- 1.56 microg/mL for each dose level. Bioavailability after the SC administration was 84 and 86% for the 10 mg/kg and the 20 mg/kg dose respectively. Considering the documented minimum inhibitory concentration (MIC(90)) range of sensitive bacteria to fosfomycin, the maximum serum concentration (Cmax) obtained (56.14 +/- 2.26 microg/mL with 10 mg/kg SC and 72.14 +/- 3.04 microg/mL with 20 mg/kg SC) and that fosfomycin is considered a time-dependant antimicrobial, it can be concluded that clinically effective plasma concentrations might be obtained for up to 10 h administering 20 mg/kg SC. An additional predictor of efficacy for this latter dose and route, and considering a 12 h dosing interval, could be area under the curve AUC(0-12)/MIC(90) ratio which in this case was calculated as 996 for the 10 mg/kg dose and 1260 for the 20 mg/kg dose if dealing with sensitive bacteria. If a more resistant strain is considered, the AUC(0-12)/MIC(90) ratio was calculated as 15 for the 10 mg/kg dose and 19 for the 20 mg/kg dose.
Zozaya
D H
DH
Departamento de Fisiología y Farmacología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Gutiérrez
O L
OL
Ocampo
C L
CL
Sumano
L H
LH
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D005260:Female; D005578:Fosfomycin / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics*; D006207:Half-Life; D006736:Horses; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008657:Metabolic Clearance Rate; D011485:Protein Binding
D000900:Anti-Bacterial Agents; D005578:Fosfomycin