Trimethoprim                                    

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Information @ a Glance

General

  • Trimethoprim is a bacteriostatic antibiotic mainly used in the prophylaxis and treatment of urinary tract infections.
  • Trimethoprim was commonly used in combination with sulfamethoxazole, a sulfonamide antibiotic, which inhibits an earlier step in the folate synthesis pathway (see diagram above). This combination, also known as co-trimoxazole, TMP-sulfa, or TMP-SMX, results in an in vitro synergistic antibacterial effect by inhibiting successive steps in folate synthesis.
  • Trimethoprim, combined with a sulfonamide (sulfadiazine or sulfamethoxazole), is an antibiotic used to treat respiratory, urinary tract, skin, and gastrointestinal infections, and infections with coccidia.
  • Trimethoprim, an antibacterial drug, is a bacterial dihydrofolate reductase inhibitor used as a prophylactic or to treat various bacterial infections particularly urinary tract infections such as Proteus mirabilis

Application

  • Trimethoprim-sulfamethoxazole(TMP-SMX), a drug regarded to be the most efficient for the chemoprophylaxis of Pneumocystis carinii pneumoniaPCP) in patients with HIV infection (5, 10, 18), stands out because of its wide use.
  • Trimethoprim is often used in combination with sulfamethoxazole to treat a wide variety of aerobic gram-positive and gram-negative infections
  • Trimethoprim, 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine(TMP), widely used in conjunction with sulfamethoxazole(SMX), is an effective antimicrobial agent used, for example, in the treatment of urinary tract infections and as a powerful bacteriostatic agent, because the antimicrobial activity is greater than that when the sulfa-drug is used alone.
  • Antibiotics were extracted by solid-phase extraction (SPE) on a polystyrene–divinylbenzene(SDB) Empore extraction disk.

Process

  • Certain benzylpyrimidines, such as trimethoprim 1 are potent and selective inhibitors of bacterial dihydrofolate reductase, the enzyme responsible for the NADPH-dependent reduction of 7,8-dihydrofolate to 5,6,7,8,-tetrahydrofolate.
  • The manufacture of Trimethoprim involves three distinct stages;starting from Gallic Acid which is converted into 3, 4, 5 Trimethoxy benzaldehyde and which in turn is converted into Trimethoprim.
  • Manufacture of 3, 4, 5 Trimethoxy benzaldehyde commences with methoxylation of Gallic Acid with Dimethyl sulphate to obtain the intermediate product 3, 4, 5 Trimethoxy benzoic acid.

Technology

  • The assays are suitable for pharmacokinetic studies and have been applied to determination of trimethoprim concentrations in serum and urine during therapy with Co-trimoxazole, a sulfonamide/ trimethoprim preparation.
  • The I... case! competitive protein binding assay technique can be used toy plasma trimethoprim concentrations with sensitivity to 0.02mg oftrimethoprim per liter.
  • Cotrimoxazole, a combination of sulfamethoxazole(SMZ) and trimethoprim (TMP), is widely used for the treatment of not only urinary tract infections, but also infections of the respiratory tract, septicemia, and gonorrhea.
  • The presence of pathogenic Vibrio cholerae is complicated by the presence in water of a large number of mostly nonpathogenic V. cholerae strains.

Market

  • The anti-infectives market is forecast to expand at a CAGR of 4.8% over the period 2005-11, driven largely by gains in the anti-bacterial and anti-viral classes.
  • With sales growth of 200.0% in 2005, Tamiflu, an established product was the strongest performing brand in Roche’s anti-infectives portfolio, with sales of $637.7m, on the back of increased demands for the product as a treatment for avian influenza.
  • The highest growth rate in the global anti-bacterials drug class was reported by the beta-lactams class of drugs which registered a growth rate of 12.8% representing sales of $1,512m in 2005, an up of $171mfrom year previous sales reported at $1,341m...

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