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 (t₁/₂β), the mean residence time (MRT), volume of distribution at steady-state (Vd₍ss₎), volume of distribution based on terminal phase (Vd₍z₎), and the total body clearance (ClB) 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 Cmax (35.47 ± 2.52 and 37.50 ± 3.39 μg/mL), tmax (2.47 ± 0.31 and 2.47 ± 0.36 h), t[fraction one₋half]β (11.79 ± 0.79 and 10.96 ± 0.56 h), Vd₍z₎/F (0.77 ± 0.06 and 0.89 ± 0.07 L/kg), ClB/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 Cmax (0.71 ± 0.06 and 0.78 ± 0.10 μg/mL), tmax (2.07 ± 0.28 and 3.27 ± 0.28 h), t[fraction one₋half]β (3.30 ± 0.25 and 3.83 ± 0.33 h), Vd₍z₎/F (6.2 ± 0.56 and 6.27 ± 0.77 L/kg), ClB/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.