Trimethoprim

Trimethoprim inhibits bacterial dihydrofolic acid reductase. Dihydrofolic acid reductases convert dihydrofolic acid to tetrahydrofolic acid, a stage leading to the synthesis of purines and ultimately to DNA.

Trimethoprim is usually given orally. It is absorbed well from the gut and distributed widely in body fluids and tissues, including cerebrospinal fluid. Trimethoprim concentrates in prostatic fluid and in vaginal fluid, which are more acid than plasma. Therefore, it has more antibacterial activity in prostatic and vaginal fluids than many other antimicrobial drugs.

Trimethoprim can be given alone in acute urinary tract infections, because most community- acquired organisms tend to be susceptible to the high concentrations.

Trimethoprim produces the predictable adverse effects of an antifolate drug, especially megaloblastic anemia, leukopenia, and granulocytopenia. This can be prevented by the simultaneous administration of folinic acid, 6-8 mg/d.