Trimethoprim

Trimethoprim (TMP) is an antibiotic that is mainly used to treat bladder infections. Other uses include middle ear infections and traveler's diarrhea. In combination with sulfamethoxazole or dapsone, it can be used for pneumocystis pneumonia in people with HIV/AIDS. It is taken by mouth. Trimethoprim is on the WHO essential medicines list and requires a prescription.

Pharmacodynamics

Trimethoprim binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF). THF is an essential building block for DNA synthesis. The affinity of trimethoprim for bacterial dihydrofolate reductase is several thousand times greater than its affinity for human dihydrofolate reductase. Thus, the effects on human DNA synthesis are comparatively small.

Pharmacokinetics

Maximum plasma concentration is usually reached at 1-4 hours after ingestion. Approximately 44% of the drug is present bound to plasma proteins. The metabolism of trimethoprim is mainly catalyzed by the enzymes CYP2C9 and CYP3A4. Excretion is largely via the urine.

Side effects

Common side effects:

• Nausea
• Taste changes
• Vomiting
• Diarrhea
• Rash
• UV sensitivity
• Itch
  
  

Rare side effects

• thrombocytopenia (low platelet count)
• megaloblastic anemia
• increased potassium levels (hyperkalemia)
• increase in serum creatinine
• use in EHEC infections may lead to increased expression of Shiga toxin

Toxicological data

LD50 (mouse, oral) 2764 mg-kg-1