Pharmacokinetics of trimethoprim/sulfadiazine in neonatal calves: influence of synovitis.

The effect of synovitis on the distribution of antibacterial drugs into the joint space was studied in 1-week-old calves. Sodium urate crystals were used to induce inflammation in the tibio-tarsal joint of calves and the antibacterial drug combination, trimethoprim/sulfadiazine (Tribrissen), 30 mg/kg, was administered intravenously 3 h after synovitis was induced. The degree of synovitis was monitored by serial WBC counts in synovial fluid. Trimethoprim (TMP) and sulfadiazine (SDZ) concentrations in serum and synovial fluid were measured and pharmacokinetic parameters were calculated. The results indicated that inflammation had no effect upon the concentrations of TMP/SDZ that reach the joint and that synovial fluid and blood are both representative of the central compartment as shown by the non-significant differences in selected pharmacokinetic parameters for TMP and SDZ in these two body fluids. The distribution and elimination of TMP and SDZ in serum were described by a two-compartment model.