Pharmacokinetics of disodium-fosfomycin in mongrel dogs.
Pharmacokinetic variables of fosfomycin were determined after administration of buffered disodium-fosfomycin intravenously (IV), intramuscularly (IM), subcutaneously (SC) and orally (PO), in mongrel dogs, at 40 and 80 mg/kgday for three days. Renal integrity was also assessed by measuring key serum variables. Day 1, day 2 and day 3 plasma concentration vs. time profiles were undistinguishable, but there appears to be a lineal increase in serum concentrations vs. time with the dose. A non-accumulative kinetic behavior was observed after three days with both doses and most pharmacokinetic variables remain unaltered. Considering a MIC range from 1 mirog/mL to 16 microg/mL of fosfomycin in serum for sensitive bacteria, and a negligible plasma protein binding of fosfomycin (<0.5%), useful plasma concentrations can only be achieved after the SC injection of 80 mg/kg every 12h, having a C(max)=18.96+/-0.3 microg/mL; a T(1/2beta)=2.09+/-0.06 microg/mL and a bioavailability of 84-85%. No alterations were observed in serum variables of kidney-related biochemical values.
Gutierrez
O L
OL
Departamento de Fisiología y Farmacología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de Mexico, Avenida Universidad 3000, Coyoacán, Mexico City 04510, Mexico.
Ocampo
C L
CL
Aguilera
J R
JR
Luna
J
J
Sumano
L H
LH
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D004285:Dogs / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D005578:Fosfomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011485:Protein Binding
D000900:Anti-Bacterial Agents; D005578:Fosfomycin