Sulfonamides formulations

The injectable formulations of potentiated sulfonamides are suspensions consequently, rapid i.v. administration causes hypotension and collapse. Fatal dysrhythmias are associated with the potentiated sulfonamides administered i.v. concurrently with the a2-adrenergic agonist deto-midine. It is suspected that the potentiated sulfonamide formulation potentiates the cardiac changes produced by detomidine. This adverse reaction has not been reported for the other ci2-adrenergic agonists xylazine and romifidine. 

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. 

Low-molecular povidones are nowadays widely used in different injectables e.g. in antibiotic and sulfonamide formulations. Fig. 54 shows, as an example, how the solubilization of rifampicin depends directly on the povidone concentration. 

Thiazine has been formulated as 1 rather than 2 because it does not form a sulfonamide under Hinsberg conditions. Symmetrical azines can form only one classical monocation, e.g., pyrazine forms 3. The nonclassical cation 4 has been postulated for pyridazine, but there is no compelling evidence in its favor. 

Contraindications Severe renal disease, adrenal insufficiency, hypochloremic acidosis, hypersensitivityto acetazolamide, to any component of the formulation, orto sulfonamides. 

Sulfadoxine is the only long-acting sulfonamide currently available in the USA and only as a combination formulation with pyrimethamine (Fansidar), a second-line agent in treatment for malaria (see Chapter 52). 

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. 

Aminosalicylates, eg, mesalamine in many formulations Mechanism uncertain t may be inhibition of eicosanoid inflammatory mediators Topical therapeutic action systemic absorption may cause toxicity Mild to moderately severe Crohn s disease and ulcerative colitis Sulfasalazine causes sulfonamide toxicity and may cause GI upset, myalgias, arthralgias, myelosuppression other aminosalicylates much less toxic... 

Following their metabolic transformation, sulfonamides are eliminated in urine, feces, bile, and milk. However, the kidney is the organ primarily involved in the excretion of these drugs. Sulfonamide residues deplete from body tissues and fluids with widely variable velocity that depends on many factors including the nature of the compound, its formulation and the route of administration, and the animal species. Nevertheless, sulfonamide residues eliminate much earlier from liver, kidney, and milk than from muscle and fat. Withdrawal periods in meat and milk differ, therefore, for each sulfonamide. 

Sulfathiazole is available for oral use and is also included in some parenteral formulations in combination with other sulfonamides. It is also used as a feed additive for growth promotion purposes. It is more toxic than sulfamethazine and sulfadimethoxine but is safe when used as the phthalyl derivative. 

The reasons for both the nicarbazin and sulfonamide contamination were not established but might result from feed contamination or on-farm management practices. The lasalocid contamination has been shown to be due to trace level carryover during feed production. As a result, the formulation of the lasalocid was changed from a powder to a granular form to reduce the carryover. 

The CHARM inhibition assay (CIA), Charm farm test (CFT), and Valio TlOl test are all simple multiresidue screening tests based on microbial inhibition (34, 35). The CIA test is actually a disc assay using Bacillus stearothermophilus and specially formulated agar media to increase the sensitivity to sulfonamides. The CFT is a tube assay using the same test organism in a specific formulation, which, along with the nutrients, is in a tablet form. To roughly identify penicillins and sulfonamides with the CIA and CFT tests, positive samples should be reanalyzed after the addition of penicillinase and p-aminobenzoic acid. 

The recognition of the quantitatively almost unmatched ability of p-aminoben-zoic acid (PABA) to oppose the bacteriostatic efficiency of the sulfonamides led Woods and Fildes [19, 20] to formulate the fundamentals of the theory of metabolite antagonism (Fig. 1.1). 

MNakane. Preparation and formulation of 7-oxabicycloheptane substituted sulfonamide prostaglandin analogs useful in treatment of thrombolic disease. U.S. Patent 4,663,336, 1987. 

An attempt to formulate a poly(4-hydroxy styrene)-based resist was less than completely successful because the difference in the rates of dissolution were too small to be used to give high contrast images. Other small molecules were added to the NDS/novolac resist and these were also found to have a profound effect upon the performance of the resist, particularly the development properties. When it was necessary to obtain higher dissolution rates, several triazoles and sulfonamides were found to improve the rate of development in the exposed areas without causing unacceptable thickness losses in the unexposed areas. Dyes incorporated to minimize problems of reflection and scattered light were also found to alter the dissolution behavior of the resist coating. 

One way to speed the dissolution is to add other components to the resist. In particular the addition of benzotriazoles and sulfonamides to a resist formulation produces a resist that appears to be more sensitive (3-5). Since sensitivity is a combination of photospeed and dissolution, an increase in sensitivity can imply either a lower exposure or a faster development from the original exposure. 

Hirayama et al. [90] made the efforts to discover FXa inhibitors, containing carboxamide and sulfonamide linkers (36-41). From their data Eq. 22 was formulated [72], where MRb is the most significant term followed by the indicator variable I-NAPH, used for the presence of a naphthyl group in the compound. Group B is indicated in the structures. 

The sulfonamides are a group of organic compounds with chemotherapeutic activity they are antimicrobial agents and not antibiotics. They have a common chemical nucleus that is closely related to PABA, an essential component in the folic acid pathway of nucleic acid synthesis. The sulfonamides are synergistic with the diaminopyrim-idines, which inhibit an essential step further along the folate pathway. The combination of a sulfonamide and a diaminopyrimidine is advantageous because it is relatively non-toxic to mammalian cells (less sulfonamide is administered) and is less likely to select for resistant bacteria. Only these so-called potentiated sulfonamides are used in equine medicine. These drugs are formulated in a ratio of one part diaminopyrimidine to five parts sulfonamide, but the optimal antimicrobial ratio at the tissue level is 1 20, which is achieved because the diaminopyrimidines are excreted more rapidly than the sulfonamides. 

In general, the sulfonamides are readily absorbed from the gastrointestinal tract of non-ruminants. Absorption may be delayed when the potentiated sulfonamides are administered with feed. Initial serum concentrations are lower in a fed horse than a fasted horse but the food effect is greatly reduced by the third treatment day. The bioavailability of one formulation of pyrimethamine is 56% following p.o. administration. 

Sulfonamides in pharmaceutical formulations have been determined by diazotization and coupling with m-aminophenol, a-naphthylamine and N- 1-naphthylethylenediamine dihydrochloride in sulfuric acid-trichloroacetic acid, and measuring the absorbance at 435, 520 and 545 nm, respectively. Absorbance is linear in the concentration... 

A colorimetric method for microdetermination of sulfonamides based on diazotization of the drug with sodium nitrite and hydrochloric acid has been reported (59). The diazonium salt is then coupled with 8-hydroxyquinoline in alkaline medium and the absorbance of the developed color measured at its maximum wavelength. A similar method involves diazotization and coupling of the sulfonamide with indole in alkaline solution to form an intense yellow azo dye which exhibits maximum absorption at 449 nm. Beer s law is obeyed over the concentration range 1-32 /ig/ml with a relative standard deviation of less than 2% (60). The reaction of sulfonamides with chloramine-T in sulfuric acid gives a yellow product which is suitable for the determination of sulfonamides in different formulations. It has an accuracy similar to that of the Bratton and Marshall method (61). 

A modified method for the determination of sulfonamides based on the Bratton-Marshall reaction with derivative spectrophotometry has been proposed (64). Various sulfonamides give excellent precision by using first- to fourth-order derivative spectra. The method has been applied to the determination of sulfonamides in pharmaceutical formulations and urine without pretreatment of the sample. 

---