trimethoprim

Research Excerpts

Overview

Trimethoprim (TMP) is a synthetic antibacterial agent that targets folate biosynthesis by competitively binding to the di-hydrofolate reductase enzyme (DHFR) TMP inhibits bacterial folic acid synthesis, but at a different stage in the metabolic pathway.

Effects

Trimethoprim has the same effect on the kidney as amiloride, a potassium-sparing diuretic, for which it is known that its combined use with lithium can result in an elevated lithium level. TrimethOPrim has been widely used since the 1960s, both alone and in combination with sulfamethoxazole.

Actions

Trimethoprim does not inhibit the biosynthesis of rT in tRNA of gram-negative Enterobacteriaceae, Rhizobium lupini, and Pseudomonadaceae. The rT-specific tRNA methyltransferases of these gram- negative strains use S-adenosylmethionine as coenzyme. TrimethOPrim may increase procainamide and N-acetylprocainamide plasma concentrations.

Treatment

Trimethoprimdapsone-treated patients had fewer treatment failures but more side effects and treatment terminations due to toxicity than those treated with dapsone alone. Treatment rarely selected resistant pathogens in the sputum or resistant Enterobacteriacae in the intestine. The incidence of resistant coagulase-negative staphylococci on the skin increased with both regimens.

Toxicity

Sulphimidazole is only slightly toxic in vitro for Vero cells. The combination of the two functional groups in a single molecule not only maintains its structure-activity relationship intact but also broadens its antibacterial spectrum.

Pharmacokinetics

Only about one-third of men with chronic bacterial prostatitis are cured of infection after prolonged therapy with trimethoprim-sulfamethoxazole. There was no clinically significant pharmacokinetic interaction between oral ganciclovir and trimethobrim when co administered.

Compound-Compound Interactions

A double-blind, multi-centre trial was carried out in 72 patients with acute or chronic infections of the lower respiratory tract. The aim was to evaluate possible antibiofilm efficacy of a gallotannin 1,2,6-tri-O-galloyl-β-D-glucopyranose.

Bioavailability

Trimethoprim bioavailability, following oral administration at 1, 6 and 12 weeks of age, is higher in milk-fed calves (non-ruminants) than in grain-fiber- fed calves (ruminant) Bioavailability decreases with increasing age in both groups of calves. The most important conclusion was that amoxycillin, chloramphenicol, and trimethop rim were suitable for oral administration to veal calves.

Dosage Studied

The new drug was given in high dosage (four tablets twice daily) for either 2 or 5 days to 20 patients with sinusitis diagnosed on clinical grounds. Successful treatment was acheived with administration of trimethoprim plus sulfamethoxazole at a dosage adjusted to the degree of renal failure.