Distribution of trimethoprim/sulphadiazine in plasma, tissue and synovial fluids

The subcutaneous implantation of tissue cages was used to study the distribution of trimethorprim and sulphadiazine into tissue (interstitial) fluid in calves, sheep and dogs over a 24-hour period. After oral dosing there was good gastrointestinal absorption of both antibacterial agents in dogs but only of the sulphonamide in sheep. The concentration of trimethoprim in tissue fluid peaked at five to seven hours after administration when it exceeded the plasma concentration. Sulphadiazine persisted in the plasma for longer than trimethoprim, but distribution into tissue fluid was slower. The findings show that reliance on plasma concentration curves alone in determinations of bioavailability of chemotherapeutic agents may lead to false interpretations.