Pharmacokinetics and bioavailability of sulfadiazine and trimethoprim following intravenous, intramuscular and oral administration in ostriches (Struthio camelus)

A pharmacokinetic and bioavailability study of sulfadiazine combined with trimethoprim (sulfadiazine/trimethoprim) was carried out in fifteen healthy young ostriches after intravenous (i.v.), intramuscular (i.m.) and oral administration at a total dose of 30 mg/kg body weight (bw) (25 and 5 mg/kg bw of sulfadiazine and trimethoprim, respectively). The study followed a single dose, three periods, cross-over randomized design. The sulfadiazine/trimethoprim combination was administered to ostriches after an overnight fasting on three treatment days, each separated by a 2-week washout period. Blood samples were collected at 0 (pretreatment), 0.08, 0.25, 0.50, 1, 2, 4, 6, 8, 12, 24 and 48 h after drug administration. Following i.v. administration, the elimination half-life (t(1/2 beta)), the mean residence time (MRT), volume of distribution at steady-state (V-d(ss)), volume of distribution based on terminal phase (V-d(z)), and the total body clearance (Cl-B) were (13.23 +/- 2.24 and 1.95 +/- 0.19 h), (10.06 +/- 0.33 and 2.17 +/- 0.20 h), (0.60 +/- 0.08, and 2.35 +/- 0.14 L/kg), (0.79 +/- 0.12 and 2.49 +/- 0.14 L/kg) and (0.69 +/- 0.03 and 16.12 +/- 1.38 mL/min/kg), for sulfadiazine and trimethoprim, respectively. No significant difference in C-max (35.47 +/- 2.52 and 37.50 +/- 3.39 mu g/mL), t(max) (2.47 +/- 0.31 and 2.47 +/- 0.36 h), t(1/2 beta) (11.79 +/- 0.79 and 10.96 +/- 0.56 h), V-d(z)/F (0.77 +/- 0.06 and 0.89 +/- 0.07 L/kg), Cl-B/F (0.76 +/- 0.04 and 0.89 +/- 0.07) and MRT (12.39 +/- 0.40 and 12.08 +/- 0.36 h) were found in sulfadiazine after i.m. and oral dosing, respectively. There were also no differences in C-max (0.71 +/- 0.06 and 0.78 +/- 0.10 mu g/mL), t(max) (2.07 +/- 0.28 and 3.27 +/- 0.28 h), t(1/2 beta) (3.30 +/- 0.25 and 3.83 +/- 0.33 h), V-d(z)/F (6.2 +/- 0.56 and 6.27 +/- 0.77 L/kg), Cl-B/F (21.9 +/- 1.46 and 18.83 +/- 1.72) and MRT (3.68 +/- 0.19 and 4.34 +/- 0.14 h) for trimethoprim after i.m. and oral dosing, respectively. The absolute bioavailability (F) was 95.41% and 86.20% for sulfadiazine and 70.02% and 79.58% for trimethoprim after i.m. and oral administration, respectively.