Sulfonamides are bacteriostatic drugs which inhibit folate synthesis. This fact means they are only effective when adequate host defences are present. Folate is an essential component of DNA synthesis. Sulfonamides contain a structural analogue of PABA (p-aminobenzoic acid) and inhibit the first part of folate synthesis. Trimethoprim interferes with
dihydrofolate reductase involved in the synthesis of tetrahydrofolate.

The primary drug interactions of note are with the following drugs
- Warfarin
- Amiodarone
- Phenytoin
- Ciclosporin
- Methotrexate, Mecaptopurine
- Azathioprine
Patients should be advised to complete the prescribed course of antibiotic therapy. Advice on the symptoms of bone marrow suppression should be given. Patients should also contact a doctor if they develop a rash.
The sulphonamides are readily absorbed in the gastrointestinal tract, they reach maximum plasma concentrations in 4-6 hours. They pass into inflammatory exudates and cross the blood brain barrier and the placental barrier. They are primarily metabolised in the liver to a metabolite that lacks antibacterial action.
Trimethoprim is also absorbed from the gastrointestinal tract. It is spread widely throughout the body tissues and reaches high concentrations in the lungs and kidneys and relatively high concentrations in the CSF. As trimethoprim is a weak base, excretion in the urine increases with decreasing urinary pH.
Excretion is renal for both groups of drugs (including Co-trimoxazole).