title: Distribution of orally administered trimethoprim and sulfadiazine into noninfected subcutaneous tissue chambers in adult ponies.
abstract: The distribution of trimethoprim (TMP) and sulfadiazine (SDZ) into subcutaneously implanted noninfected tissue chambers was studied in healthy adult ponies. Six ponies were given an oral TMP/SDZ paste formulation at a dose of 5 mg/kg TMP and 25 mg/kg SDZ at 12 h intervals for 2 days in order to reach steady-state concentrations. Plasma concentrations and tissue chamber fluid (TCF) concentrations of both drugs were measured at regular intervals during a period commencing 24 h after the last oral administration. The peak concentration of TMP (mean +/- SD) was 2.92 +/- 0.86 microg/mL for plasma and 1.09 +/- 0.25 microg/mL for TCF. For SDZ, the mean peak concentration was 40.20 +/- 14.74 microg/mL for plasma and 23.48 +/- 5.84 microg/mL for TCF. TMP peak concentrations in plasma were reached at 3.17 +/- 03.48 h and those in TCF at 7.33 +/- 03.72 h. SDZ peak concentrations in plasma were reached at 1.83 +/- 02.04 h and those in TCF at 8.00 +/- 03.10 h. Concentrations of TMP and SDZ in TCF remained above the generally accepted breakpoint for susceptibility (0.5/9.5 for the TMP/SDZ combination) for 12 h. Therefore, in ponies oral administration of TMP/SDZ at a dose rate of 30 mg/kg given twice daily in the form of a paste should be appropriate for effective treatment of infections caused by susceptible bacteria.
authors.affiliation: Bacteriology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, the Netherlands. e.duijkeren@vet.uu.nl
authors.forename: E
authors.initials: E
authors.lastname: van Duijkeren
authors.forename: J M
authors.initials: JM
authors.lastname: Ensink
authors.forename: L A
authors.initials: LA
authors.lastname: Meijer
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000892:Anti-Infective Agents, Urinary / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004338:Drug Combinations; D005260:Female; D006207:Half-Life; D006736:Horses; D008297:Male; D013411:Sulfadiazine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014295:Trimethoprim / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000096926:Benzenesulfonamides
chemical_list: D000892:Anti-Infective Agents, Urinary; D004338:Drug Combinations; D013411:Sulfadiazine; D014295:Trimethoprim; C024873:sulfadiazine, trimethoprim drug combination; D000096926:Benzenesulfonamides