Trimethoprim formulations

Therefore, when 1 part of trimethoprim is given with 5 parts of sulfamethoxazole (the ratio in the formulation), the peak plasma concentrations are in the ratio of 1 20, which is optimal for the combined effects of these drugs in vitro. About 30-50% of the sulfonamide and 50-60% of the trimethoprim (or their respective metabolites) are excreted in the urine within 24 hours. The dose should be reduced by half for patients with creatinine clearances of 15-30 mL/min. 

Trimethoprim- sulfamethoxazole Synergistic combination of folate antagonists blocks purine production and nucleic acid synthesis Bactericidal activity against susceptible bacteria Urinary tract infections Pneumocystis jiroveci pneumonia toxoplasmosis nocardiosis Oral, IV renal clearance (half-life 8 h) dosed every 8-12 h t formulated in a 5 1 ratio of sulfamethoxazole to trimethoprim Toxicity Rash, fever, bone marrow suppression, hyperkalemia... 

C. Akay and S. A. Ozkan, Simultaneous LC determination of trimethoprim and sulphamethoxazole in pharmaceutical formulations J. Pharm. Biomed. Anal. 30 (2002), 1207-1213. 

Other drugs studied by Moore et al. include chlorine containing photosensitizers (178), the effect of surfactants on photosensitizers (179), photosensitization by malarial drugs (180), nalidic and oxolinic acids (181), 6-mercaptopurine (182), azathioprine and nitroimidazole (183), 7-methylbenz[c]acridine and related products (184), naproxen, ben-oxaprofen and indomethacin (185), mefloquine (186), sulfamethoxazole and trimethoprim (187), benzydamine (188), photodecomposition of hydrochlorthiazide (189), tetracycline (190), frusemide (191), 6-mercaptopurine (192), 7-methylbenz[c]acridine (193), metronidazole, misonidazole and azathioprine (194), misonidazole and metronidazole (195), benzydamine (196), components in drug formulations (197) and sulfamethoxazole (198,199). 

It is important to consider the influence of interaction between functional groups of drugs that leads to their habit modification when formulated in suspension dosage form. Proton transfer from the N atom of sulfamethoxazole to the pyrimidine basic N1 atom of trimethoprim has been reported to occur in their equimolar complexes. Bettinetti et al. have reported nucleation of the complex of trimethoprim and sulfa-methoxypyridazine (1 1) to be accelerated by water or wet granulation. Our studies on cotrimoxazole (unpublished results) revealed immediate formation of fine needle-shaped crystals irrespective of the initial shape of sulfamethoxazole and trimethoprim crystals as a result of the interaction between the two drugs in suspension form. Small needles (Fig. 6A) were... 

Oral paste and powder formulations of trimethoprim/sulfadiazine are approved for use in horses. An injectable suspension of trimethoprim/sulfadiazine (48%) is available for i.v. or i.m. administration to horses. Injections must be administered slowly i.v. to avoid collapse and i.m. 

Shoaf S E. Schwark W S, Guard C L 1989 Pharmacokinetics of sulfadiazine/trimethoprim in neonatal male calves effect of age and penetration into cerebrospinal fluid. American Journal of Veterinary Research 50 396-402 Taylor W M, Simpson C F, Martin F G 1972 Certain aspects of toxicity of an amicarbalide formulation to ponies. American Journal of Veterinary Research 33 533-541 Watkins W M, Mosobo M 1993 Treatment of Plasmodium falciparium malaria with pyrimethamine and sulphadoxine a selective pressure for resistance is a function of long elimination half-life. Transactions of the Royal Society of Tropical Medicine and Hygiene 87 75-79... 

In the past, EPM was treated using a trimethoprim-containing potentiated sulfonamide in combination with pyrimethamine, mainly because of the difficulty in finding sulfonamide formulations without trimethoprim. However, trimethoprim adds little to the antisarcocystis activity but is believed to increase the risk of hematological toxicity (Fenger et al 1997). Currently, there are numerous veterinary pharmacies in the USA that will compoimd pyrimethamine with sulfadiazine for the treatment of horses with EPM. 

Tables 95 and 96 give formulations for acetaminophen and diclofenac oral solutions that were developed on a laboratory scale, as typical examples. In the case of acetaminophen, povidone not only solubilizes the active substance, it also reduces its bitter taste [625]. Similar effects are described in the case of sul-famethoxazol and trimethoprim [21,625].

Tiwary AK, Panpalia GM. Influence of crystal habit on trimethoprim suspension formulation. Pharm Res 1999 16 261-265. 

As patients improve clinicaUy, the route of administration should be reevaluated. Streamlining therapy from parenteral to oral (switch therapy) has become an accepted practice for many infections outside the bloodstream and CNS. Criteria that should be present to justify a switch to oral therapy include (1) overall clinical improvement, (2) lack of fever for 24 to 48 hours, (3) decreased WBC count, and (4) a functioning gastrointestinal tract. Drugs that exhibit excellent oral bioavaUabifity when compared with intravenous formulations include ciprofloxacin, clindamycin, doxycycline, gatifloxacin, levofloxacin, metronidazole, moxifloxacin, linezolid, and trimethoprim-sulfamethoxazole. 

It is a pharmacopoeial requirement that suspensions should be redispersible if they settle on storage. However, the pharmacopoeias do not offer a suitable test that can be used to characterize this aspect of the formulation. In an attempt to remedy this situation, Deicke and Stiverkrtip (1999) have devised a mechanical redispersibility tester, which closely simulates the action of human shaking. The crystal habit may also affect the physical stability of the formulation Tiwary and Panpalia (1999) showed that trimethoprim crystals with the largest aspect ratio showed the best sedimentation volume and redispersibility. 

Trimethoprim inhibits another enzyme, dihydrofolate reductase, in the same folic acid metabolic pathway. Folic acid is converted into folate, which then has to be converted into an activated form by dihydrofolate reductase. In this way, trimethoprim interferes with the conversion of folate into its activated form, which is a cofactor in the synthesis of bacterial DNA. Dihydrofolate reductase also occurs in host cells, but it is less sensitive to trimethoprim. Trimethoprim is used to treat urinary tract infections. It is also formulated in combination with a sulphonamide, when it is known as co-trimoxazole, to treat pneumonia in patients with HIV (see page 170). Due to the synergistic effect of the two drugs, this combination is more effective than either drug alone. 

Shah, K.P. Chang, M. Riley, C.M. Automated analytical systems for drug development studies. II-A system for dissolution testing. J.Pharm.Biomed.Anal., 1994,12,1519-1527 [dissolution testing formulations tablets also sulfamethoxazole, trimethoprim]... 

Mokry, M. KUmes, J. Zahradnicek, M. HPLC anal3rsis of some sulfonamides in selected pharmaceutical formulations. Pharmazie, 1994, 49, 333—335 [tablets injections acetanilide (IS) simultaneous trimethoprim also phenacetin, phenazone, phenohenbital, phthalylsulfathiazole, sulfadimidine, sulfa-metho diazine, sulfamoxole, sulfisoxazole]... 

Tolymyxin B is formulated for delivery in combination with bacitracin, neomycin, gramicidin, oxytetracycline, or trimethoprim. See Chapters 43 through 46 for further discussion of these antibacterial agents. 

Drugs are usually called by their recommended or proposed International Non-proprietary Names (rINN or pINN) when these are not available, chemical names have been used. If a fixed combination has a generic combination British Approved Name (e.g. co-trimoxazole for trimethoprim -I- sulfamethoxazole) that name has been used in some cases brand names have been used instead. When the plus symbol (-I-) is used to link drug names (for example, lopinavir -I- ritonavir ), it impUes that the two drugs are administered either in one formulation or in conjunction with one another otherwise the word plus is used. 

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