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.

Intramuscular dosing strategy for ampicillin sodium in horses, based on its distribution into tissue chambers before and after induction of inflammation

“…In the present study, we observed a slow rise and a slow decline in ampicillin concentrations in TCF, similar to the findings of Ensink et al. (1996a) and a feature that is considered characteristic for TCF (Bengtsson & Greko, 2002; Van Duikeren et al. , 2002).…”

Clinical efficacy of prophylactic administration of trimethoprim/sulfadiazine in a Streptococcus equi subsp. zooepidemicus infection model in ponies

“…In an earlier pharmacokinetic study with uninfected tissue chambers, drug concentrations were approximately 1 μ g/mL TMP and 20 μ g/mL SDZ throughout the dosing interval of 12 h (van Duijkeren et al. , 2002).…”

“…On D1 and D3 the concentrations in these two ponies had also reached the levels of 1 μ g/mL TMP and 20 μ g/mL SDZ. On the basis of these concentrations it would be expected that this dosage regimen would be effective against all susceptible bacteria, with MIC s of ≤0.5/9.5 μ g/mL of TMP/SDZ (van Duijkeren et al. , 2002).…”

“…Samples of TCF for analysis of TMP and SDZ were stored in heparinized tubes at −80 °C until assayed. Concentrations of TMP and SDZ were determined by high performance liquid chromatography with detection by mass spectrometry as described earlier (van Duijkeren et al. , 2002).…”

A randomized controlled field trial of a novel trimethoprim-sulfadiazine oral suspension for treatment of Streptococcus equi subsp zooepidemicus infection of the lower respiratory tract in horses

“…1,2 The combination of a sulfonamide with trimethoprim results in bactericidal activity with lower MICs for each drug. 4 A study 5 evaluating trimethoprim-sulfadiazine paste administered orally to healthy adult ponies indicated that a dosage of 30 mg/ kg administered twice daily results in continuous therapeutic concentrations in subcutaneous tissue chambers for 12 hours. 3 When administered at a dosage of 30 mg/kg (13.6 mg/lb) orally twice daily, therapeutic plasma concentrations are maintained.…”