title: Application of in vivo microdialysis for investigation of unbound drug concentrations of intravenously administered sulfadimidine in the paranasal sinus mucosa of horses.
abstract: OBJECTIVE
  To monitor concentrations of sulfadimidine in the paranasal sinus mucosa (PSM) of unsedated horses following IV administration of trimethoprim-sulfadimidine via in vivo microdialysis.
  
  
  METHODS
  10 healthy adult horses.
  
  
  METHODS
  Concentric microdialysis probes were implanted into the subepithelial layers of the frontal sinus mucosa of standing sedated horses. Four hours after implantation, trimethoprim-sulfadimidine (30 mg/kg) was administered IV every 24 hours for 2 days; dialysate and plasma samples were collected at intervals during that 48-hour period and analyzed for concentrations of sulfadimidine. The dialysate concentration and relative loss of sulfadimidine from the perfusate were used to calculate the PSM concentration.
  
  
  RESULTS
  Microdialysis probe implantation and subsequent in vivo microdialysis were successfully performed for all 10 horses. Following the first and second administration of trimethoprim-sulfadimidine, mean ± SD peak concentrations of sulfadimidine were 55.3 ± 10.3 μg/mL and 51.5 ± 8.7 μg/mL, respectively, in plasma and 9.6 ± 4.5 μg/mL and 7.0 ± 3.3 μg/mL, respectively, in the PSM. Peak sulfadimidine concentrations in the PSM were detected at 5.9 ± 2.7 hours and 5.4 ± 2.3 hours following the first and second drug administrations, respectively. For 12 hours, mean PSM sulfadimidine concentration remained greater than the minimum inhibitory concentration indicative of sulfonamide susceptibility of equine bacterial isolates (4.75 μg/mL).
  
  
  CONCLUSIONS
  In vivo microdialysis for continuous monitoring of PSM sulfadimidine concentrations in unsedated horses was feasible. Intravenous administration of trimethoprim (5 mg/kg) and sulfadimidine (25 mg/kg) proved likely to be efficient for treating sinusitis caused by highly susceptible pathogens, providing that the dosing interval is 12 hours.
authors: Clinic for Horses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
authors: Astrid
authors: A
authors: Bienert-Zeit
authors: Caroline
authors: C
authors: Gietz
authors: Carsten
authors: C
authors: Staszyk
authors: Manfred
authors: M
authors: Kietzmann
authors: Jessica
authors: J
authors: Stahl
authors: Bernhard
authors: B
authors: Ohnesorge
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006736:Horses / Q000378:metabolism*; D008297:Male; D008826:Microbial Sensitivity Tests; D017551:Microdialysis / Q000662:veterinary; D009092:Mucous Membrane / Q000378:metabolism; D010256:Paranasal Sinuses; D013418:Sulfamethazine / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000890:Anti-Infective Agents; D013418:Sulfamethazine