ATC Vet Code: QJ01EW10

Sulfadiazine (SDZ) inhibits the incorporation of para-aminobenzoic acid into folic acid and trimethoprim (TMP) inhibits the enzyme dihydrofolate reductase (DHFR) which converts dihydrofolic acid into tetrahydrofolic acid. TMP and SDZ act together synergistically with a double-blockade mode of action. The combination is bactericidal, inhibiting sequential steps in the synthesis of purines which are required for DNA synthesis. TMP/SDZ combinations have a broad bactericidal action against many gram-positive and gram-negative aerobic bacteria, and a large proportion of anaerobic bacteria.

Sulfadiazine is moderately well absorbed after oral administration (rapidly by sheep and pigs but more slowly by cattle), is protein bound only to a limited extent and is well distributed. Metabolism occurs in the liver and the major products are acetylated derivatives which are excreted mainly by glomerular filtration. The plasma half lives in cattle, pigs and dogs are 2 - 3 and 4 hours respectively. The half-life when given to horses in combination with Trimethoprim is 3 hours. Trimethoprim is a weak base with low water solubility. It is readily absorbed from the gastro-intestinal tract, although it is degraded in the rumen. Trimethoprim is about 65% protein bound but, being lipid soluble, readily penetrates cellular barriers to become widely distributed. It is partly oxidised and conjugated in the liver and the metabolites, plus unchanged Trimethoprim are excreted in the urine.

The degree of metabolism varies: 80% in the dog and almost 100% in the cow. The half-life is also variable: 4 hours in the horse, 2 hours in the pig and 1 hour in the cow.

Given the wide interspecies variability in the half-life of both actives, it is not possible to attain pharmacokinetic matching of the two compounds, but there is evidence that synergism occurs over a wide range of dose ratios. The combination of 1:5 Trimethoprim:Sulfadiazine is well documented for veterinary use.