Trimethoprim API Manufacturers & Suppliers

Trimethoprim (CAS 738-70-5) is an antifolate antibacterial agent used primarily for the treatment of uncomplicated urinary tract infections caused by susceptible gram‑negative organisms and coagulase‑negative staphylococci. In fixed‑dose combinations with sulfamethoxazole, it is applied to a broader range of infections including acute otitis media in children, acute exacerbations of chronic bronchitis in adults, shigellosis, travelers’ diarrhea due to enterotoxigenic Escherichia coli, and the prophylaxis or treatment of Pneumocystis jiroveci pneumonia. Ophthalmic formulations combined with polymyxin B are used for acute bacterial conjunctivitis, blepharitis, and blepharoconjunctivitis.

Pharmacologically, trimethoprim is a selective inhibitor of bacterial dihydrofolate reductase. By preventing the reduction of dihydrofolic acid to tetrahydrofolic acid, it disrupts folate‑dependent steps required for bacterial DNA and protein synthesis. As monotherapy it is generally bacteriostatic, while coadministration with sulfamethoxazole yields sequential blockade of folate synthesis and is considered bactericidal. Its activity encompasses several Enterobacterales species and staphylococci, although resistance can occur through altered DHFR enzymes, enzyme overproduction, or permeability changes. Local susceptibility data are important for guiding use.

Trimethoprim is rapidly absorbed after oral administration, with distribution into tissues and body fluids. It undergoes partial hepatic metabolism and is eliminated predominantly via the kidneys, with both parent drug and metabolites appearing in urine. Renal clearance mechanisms involve OCT2 and MATE transporters. Plasma protein binding is moderate, and the compound is a substrate and inhibitor of several CYP and transporter pathways, creating potential for drug interactions.

Safety considerations include the risk of hematologic abnormalities such as thrombocytopenia or leukopenia, particularly with prolonged therapy or folate deficiency. Hyperkalemia may occur due to trimethoprim’s effects on renal potassium handling. Photosensitivity reactions have been reported.

For API procurement, manufacturers should verify compliance with pharmacopeial monographs, demonstrate control of stereochemistry and related substances, and ensure robust impurity profiling and microbial controls appropriate for an antifolate antimicrobial.