National Toxicology Program

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. ¹

Names (NTP)

• Sulfathiazole
• 4-AMINO-N-2-THIAZOLYL-BENZENESULFONAMIDE (9CI)

Human Toxicity Excerpts

• None found

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Non-Human Toxicity Excerpts

• IN DOMESTIC MAMMALS, MOST COMMON FORM /OF CHRONIC SULFONAMIDE TOXICITY/ IS RENAL OBSTRUCTION DUE TO DEPOSITION OF SULFONAMIDE CRYSTALS... IT IS POSSIBLE IN CASE OF...SULFATHIAZOLE, IN WHICH SOLUBILITY IS GREATLY INCR IN ALKALINE URINE, TO PREVENT DEVELOPMENT OF CRYSTALLURIA...BY SIMULTANEOUS ALKALI THERAPY. [Clarke, E.G., and M. L. Clarke. Veterinary Toxicology. Baltimore, Maryland: The Williams and Wilkins Company, 1975., p. 170]**PEER REVIEWED**
  
• SULFATHIAZOLE 2% IN DIET TO MICE FOR 14 DAYS INCR CHOLESTEROL FORMATION IN PAROTID, SUBMANDIBULAR, & SUBLINGUAL GLANDS BUT DECR FORMATION IN LIVER. FECAL EXCRETION WAS DECR. [SUMIDA J, NAKAMURA H; SHIKA KISO IGAKKI ZASSHI 19 (4): 561 (1977)]**PEER REVIEWED**
  
• SULFATHIAZOLE WAS FOUND TO INHIBIT KALLIKREIN (KALLIDINOGENASE) ACTIVITY IN VITRO. [KRZEK J; FARM POL 33 (AUG): 493 (1977)]**PEER REVIEWED**
  
• INJECTED INTO FERTILIZED EGGS SULFATHIAZOLE EXHIBITED GROWTH DEPRESSING & LETHAL EFFECTS ON THE EMBRYOS, ALSO EXERTED TERATOGENIC EFFECTS HYDROPS & BILL ABNORMALITIES. [CHOY I; SHOWA IGAKKAI ZASSHI 35 (3): 187 (1975)]**PEER REVIEWED**
  
• Sulfathiazole was tested for mutagenicity in the Salmonella/microsome preincubation assay using the standard protocol approved by the National Toxicology Program. Sulfathiazole was tested at doses of 1.0, 3.0, 10, 16, and 33 ug/plate in as many as 5 Salmonella typhimurium strains (TA1535, TA1537, TA97, TA98, and TA100) in the presence and absence of rat or hamster liver S-9. Sulfathiazole was negative in these tests and the highest ineffective dose tested in any S. typhimurium strain was 33 ug/plate. The solvent used was DMSO and both a solvent and a postivie control group were included in this experiment. [Mortelmans K et al; Environ Mutagen 8:1-119 (1986)]**PEER REVIEWED**
  
• The guinea pig maximization test is one of the preferred test methods for the identification of skin sensitizers. The OECD/EC test guidelines allow for the conduct of a rechallenge in case doubtful reactions are obtained after challenge. The relevance of rechallenging was investigated by performing multiple challenges (up to four) in the maximization test with four well-known sensitizers of varying strength: nickel sulfate, sulfathiazole, benzocaine, and 1-chloro-2,4-dinitrobenzene. In addition, the effect of sodium lauryl sulfate (SLS)-pretreatment during topical induction with weak sensitizers on rechallenging was investigated. In contrast to what has frequently been hypothesized, rechallenge did not result in an increase of skin reaction as compared with the reactions observed after the first treatment. sodium lauryl sulfate pretreatment was very effective in increasing the initial challenge response to weak sensitizers. Subsequent rechallenging in these cases however again showed a decrease in sensitivity of the animals. [Prinsen MK et al; Food Chem Toxicol 35 (9): 923-6 (1997)]**PEER REVIEWED**
  
• Urine levels of silver and sulfathiazole were measured in thermal injured guinea pigs who were treated with 500 mg/day silver sulfathiazole (Argosulfan) cream for 7 days. Very small amounts of silver and significant quantities of sulfathiazole were detected in the urine. The mean content of silver in 1 ml urine was 2.26 mcg and the corresponding average daily excretion of silver in the urine amounted to 62.72 mcg/24 hr. The mean concentration of sulfathiazole in urine was 226 mcg/ml, corresponding to daily amounts averaging 5.43 mg. [Stozowska W et al; STP Pharma Sci 5 (6): 452-455 (1995)]**PEER REVIEWED**
  
• Guinea pig assays have been used extensively to detect contact sensitizers. In contrast, almost no reliable assays are available to detect the potential for low-molecular-weight drugs and chemicals to induce systemic allergic reactions in humans. Based on clinical data, and, to some extent, on recent immunological findings, it is proposed that guinea pig assays can predict the hazard for systemic allergic reactions in man. Seventy drug and chemicals were compared from published results in guinea pig assays and in the clinic. A close correlation was found with 43 substances and a relatively good one with 16 substances. Conflicting results were found with 11 substances only. However, substances known to induce systemic allergic reactions in man were all detected as weak sensitizers, at least in guinea pigs. Guinea pig contact sensitization assays may therefore prove useful until more suitable and specific assays are available to predict the risk for systemic allergic reactions. [Vial T, Descotes J; Toxicology 93 (1): 63-75 (1994)]**PEER REVIEWED**
  
• The study was done on 60 strains of Bacillus cereus isolated from cases of food poisoning and from food products tested in current supervision. The highest sensitivity was found to the antibiotics: streptomycin, neomycin, gentamicin, amikacin, oxytetracycline, and sulfonamides: negram and sulfathiazole. All strains were resistant to colistin and cloxacillin, nearly all were resistant to penicillin, ampicillin and optochine. [Stec E; Rocz Panstw Zakl Hig 41 (5-6): 269-72 (1990)]**PEER REVIEWED**
  
• In experimental toxic hepatitis induced by injection of CCl4 into rats, the rat blood and urine content of acetylated sulfamonomethoxine diminishes, the acetylation os sulfamonomethoxine and norsulfazole in an isolated stomach of the rat reduces, and acetylation of sulfamonomethoxine is inhibited by rat liver and small intestine e homogenates. This confirms that different types of pathology (infectious and non-infectious) provoke the same line of changes, namely the reduction of acetylation of sulfanilamide substances in the body. CCl1 decreases sulfamonomethoxine acetylation by a mixtures of the mitochondria and microsomes of the rat liver, i.e., eliminated the synergistic effect characteristic for intact rats. The reduction of acetylation recorded at different levels of the organization of the living systems--bodily, organ and subcellular ones--is accounted for by the lowering of the acetylcoenzyme A content in the tissues. One of the reasons for reduction of acetylation during the CCl4-induced liver injury lies in the impairment in the liver cells of the interaction between the mitochondria and endoplasmic reticulum. [Makarov VA et al; Farmakol Toksikol 47 (5): 60-3 (1984)]**PEER REVIEWED**
  

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Human Toxicity Values

• None found

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Non-Human Toxicity Values

• LD50 Mouse oral 4500 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 3154]**PEER REVIEWED**
  

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Absorption, Distribution and Excretion

• THE PHARMACOKINETIC BEHAVIOR OF SULFATHIAZOLE...IN SHEEP FOLLOWING SINGLE PARENTERAL & ORAL DOSAGE HAS BEEN REPORTED. THE DRUG UNDERWENT ACETYLATION, & BOTH THE PARENT DRUG & ACETYL DERIVATIVE WERE RAPIDLY ELIMINATED VIA KIDNEYS. [The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 5: A Review of the Literature Published during 1976 and 1977. London: The Chemical Society, 1979., p. 386]**PEER REVIEWED**
  
• FOLLOWING SINGLE IV INJECTION IN BUFFALOES (100 MG/KG), SULFATHIAZOLE WAS RAPIDLY ELIMINATED, WITH T/2 OF 198 MIN, VOL OF DISTRIBUTION WAS 452 ML/KG, & 24 HR AFTER 10.10 UG/ML WAS FOUND IN PLASMA. HIGH CONCN OF PARENT & ACETYLATED DERIV WAS FOUND IN URINE. [ATEF M ET AL; ZENTRALBL VETERINAERMED, REIHE A 28 (2): 122 (1981)]**PEER REVIEWED**
  
• PLASMA, URINE, & TISSUE SULFATHIAZOLE CONCN WERE DETERMINED FOLLOWING IV ADMIN TO 12 SHEEP, WITH ELIMINATION T/2 OF 1.1 HR & VOL DISTRIBUTION OF 0.39 L/KG. ELIMINATION WAS BY EXCRETION OF UNCHANGED DRUG IN URINE (67%) & BY FORMATION OF 2 METABOLITES. [BEVILL RF ET AL; J PHARM SCI 66 (9): 1297 (1977)]**PEER REVIEWED**
  
• SULFATHIAZOLE WAS EXCRETED THROUGH THE RUMINAL WALL & SALIVARY GLANDS IN COWS, BEING ACETYLATED (16.2%) & RAPIDLY EXCRETED (2 HR). [ATEF M ET AL; ZENTRALBL VETERINAERMED REIHE A 28 (2): 113 (1981)]**PEER REVIEWED**
  
• BINDING OF SULFATHIAZOLE TO BOVINE WHOLE BLOOD, PLASMA PROTEINS, & PURIFIED ALBUMIN FRACTION WAS INVESTIGATED USING A DYNAMIC DIALYSIS SYSTEM. BINDING WAS SIGNIFICANTLY GREATER IN PLASMA THAN IN SOLN OF FRACTION V BOVINE ALBUMIN. [CRUZE CA, MEYER MC; J PHARM SCI 65 (JAN): 33 (1976)]**PEER REVIEWED**
  
• WHEN SULFATHIAZOLE WAS INJECTED INTO THE FEMORAL VEIN OF RATS IT WAS DETECTED 6 HR LATER IN THE BILE, THE EXCRETION WAS 1.3%. [CANTELLI FORTI G, BIAGI GL; BOLL SOC ITAL BIOL SPER 48 (24): 1233 (1972)]**PEER REVIEWED**
  
• RATE CONSTANTS OF ACETYLATION & EXCRETION FOR SULFATHIAZOLE WAS STUDIED IN INBRED RATS. EXCRETION RATE AFTER IV ADMIN WAS MARKEDLY INFLUENCED BY URINARY PH IT DOUBLED WHEN URINARY PH WAS INCR TO 8.6. SULFONAMIDES MAY BE REABSORBED FROM RENAL TUBULE IN THE UNIONIZED FORM. [YAMAZAKIM ET AL; CHEM PHARM BULL 16 (4): 721 (1968)]**PEER REVIEWED**
  
• SULFATHIAZOLE-N4-ACETATE HAD A LOWER CLEARANCE RATIO THAN SULFATHIAZOLE, N4-ACETYLATED PRODUCT WAS EXCRETED CONSIDERABLY THROUGH PROXIMAL TUBULES. [ARITA T ET AL; CHEM PHARM BULL 20 (3): 570 (1972)]**PEER REVIEWED**
  
• RENAL CLEARANCE OF SULFATHIAZOLE IN PIGS WAS MARLEDLY DECR DURING INFUSION OF E COLI ENDOTOXIN, WHILE THE INULIN CLEARANCE WAS INAFFECTED. [FRIIS C, LADEFOGED O; ZENTRALBL VETERINAERMED, REIHE A 26 (2): 146 (1979)]**PEER REVIEWED**
  
• EFFECTS OF ENDOTOXIN-INDUCED FEVER IN 5 ENDOTOXIN-MODELS IN RABBITS &/OR PIGS DEPENDS ON THE ANIMAL SPECIES & THE TEST DRUG APPLIED. [LADEFOGED O; DEV ANIM VET SCI 6(TRENDS VET PHARMACOL TOXICOL) 70 (1980)]**PEER REVIEWED**
  
• Sulfonamides are absorbed through the vaginal mucosa. /Sulfonamides/ [USP Convention. USPDI - Drug Information for the Health Care Professional. 17th ed. Volume I. Rockville, MD: Convention, Inc., 1997. (Plus Updates)., p. 2698]**PEER REVIEWED**
  
• SULFONAMIDES ARE ELIMINATED FROM BODY PARTLY AS SUCH & PARTLY AS METABOLIC PRODUCTS. LARGEST FRACTION IS EXCRETED IN URINE, & HALF LIFE ... IS THUS DEPENDENT ON RENAL FUNCTION. SMALL AMT ARE ELIMINATED IN FECES & IN BILE, MILK, & OTHER SECRETIONS. /SULFONAMIDES/ [Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1059]**PEER REVIEWED**
  
• ALL SULFONAMIDES ARE BOUND IN VARYING DEGREE TO PLASMA PROTEINS, PARTICULARLY TO ALBUMIN. EXTENT ... IS DETERMINED BY HYDROPHOBICITY ... & ITS PKA ... IN GENERAL, SULFONAMIDE IS BOUND TO SOMEWHAT GREATER EXTENT IN ACETYLATED THAN IN FREE FORM. /SULFONAMIDES/ [Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1059]**PEER REVIEWED**
  
• SULFONAMIDES ARE DISTRIBUTED THROUGHOUT ALL TISSUES OF BODY. ... READILY ENTER PLEURAL, PERITONEAL, SYNOVIAL, OCULAR, & SIMILAR BODY FLUIDS, & MAY REACH CONCN THAT ARE 50-80% OF SIMULTANEOUSLY DETERMINED BLOOD CONCN. ... ATTAIN CEREBROSPINAL FLUID CONCN THAT ARE EFFECTIVE IN MENINGEAL INFECTIONS. /SULFONAMIDES/ [Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1059]**PEER REVIEWED**
  
• SULFONAMIDES READILY PASS THROUGH PLACENTA & REACH FETAL CIRCULATION. EQUILIBRIUM BETWEEN MATERNAL & FETAL BLOOD IS USUALLY ESTABLISHED WITHIN 3 HR AFTER SINGLE ORAL DOSE. CONCN ATTAINED IN FETAL TISSUES ARE SUFFICIENT TO CAUSE BOTH ANTIBACTERIAL & TOXIC EFFECTS. /SULFONAMIDES/ [Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1059]**PEER REVIEWED**
  
• ... THIS CLASS OF DRUGS IS RAPIDLY & ADEQUATELY ABSORBED FROM GI TRACT. INDEED, AGENT CAN OFTEN BE FOUND IN URINE WITHIN 30 MIN AFTER ITS ORAL INGESTION. SMALL INTESTINE IS MAJOR SITE OF ABSORPTION, BUT SOME OF DRUG IS ABSORBED FROM STOMACH. /SULFONAMIDES/ [Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1059]**PEER REVIEWED**
  
• Solid dispersions of sulfathiazole in povidone (polyvinylpyrrolidone) were prepared by mechanical activation and characterized in vitro. The apparent solubility and rate of solvation of sulfathiazole were greatly increased when it was previously mechanically treated with povidone. As the fraction of povidone increased, the efficiency of mechanicochemical action increased. Drug release from solid dispersions with a polymer to drug ratio of 1:3, 1:1, and 3:1 was examined, a polymer to drug ratio of 3:1 gave the highest solubility. It was concluded that the preparation of sulfathiazole-povidone solid dispersions by mechanical activation significantly enhances drug solubility. [Boldyrev VV et al; Drug Dev Ind Pharm 20 (6): 1103-1114 (1994)]**PEER REVIEWED**
  
• The plasma pharmacokinetics and tissue penetration of sulfathiazole (ST) and sulfamethazine(SM) after intravenous and intramuscular injection in pigs were studied. Following a single intravenous does of 40 mg sulfathiazole/kg of bodyweight or 80 mg sulfamethazine/kg of bodyweight, the plasma sulfathiazole and sulfamethazine concentrations were best fitted to a two-compartment model. The areas under the curve were 447 +/- 39 and 1485 +/- 41 mg/hr/l, clearances were 0.090 +?- 0.007 and 0.054 +/- 0.001 L/kg/hr, volumes of distribution were 1.16 +/- 0.16 and 0.77 +/- 0.06 l/kg, half-lifes in distribution phase were 1.18 +/- 0.57 and 0.23 +/- 0.16 hr and half-lifes in eliminations phase were 9.0 +/- 1.6 and 9.8 +/- 0.6 hr. When the two compounds were administered simultaneously as a single intravenous injection, the pharmacokinetic parameters for sulfathiazole were not significantly different. The values for sulfamethazine show statistical difference for some important parameters: alpha, beta and the AUCO-> were significantly decreased and t1/2alpha, Vd and ClB were significantly increased. It can be concluded that after a single intravenous injection of 40 mg/kg, sulfathiazole has a high t1/2beta resulting in higher tissue concentrations. This half-life, which is higher than what is reported in the literature, is not influenced by the presence of sulfathiazole. Sulfathiazole and sulfamethazine were also administered simultaneously as an intramuscular injection to healthy pigs at a dosage of 40 and 80 mg/kg bodyweight. Pharmacokinetic experiments were conducted on three pigs. From this pharmacokinetic study it can be concluded that upon a single intramuscular administration of 40 mg/kg of sulfathiazole and 80 mg/kg of sulfamethazine the absolute bioavailability in pigs is 0.92 +/- 0.04 for sulfathiazole and 1.01 +/- 0.07 for sulfamethazine. Six pigs received five intramuscular (im) injections, as a single dose of sulfathiazole and sulfamethazine, every 24 hr for five consecutive days for the residue study. The pigs were slaughtered at different times after the last dose was given, and samples were taken from various tissues and organs. Concentrations were determined by a microbiological method and a HPTLC method. No edible tissue contained more than 100 mug/kg of the individual sulfonamides after 10 days of withdrawal. It means that adult animals, which have a shorter half-life and, thus, lower tissue concentrations, will certainly meet the economic community (EC) maximum residue limits after a 10 days withdrawal period. [Van Poucke LSG, Van Peteghem CH; Journal of Food Protection 57 (9): 796-801 (1994)]**PEER REVIEWED**
  
• The effects of drug and diluent solubility on the activity of binders were studied using granules containing povidone (PVP; polyvinylpyrrolidone) and hydroxypropyl methylcellulose as binders, sulfathiazole and sulfathiazole sodium as model drugs, and lactose and calcium phosphate dibasic (dicalcium phosphate) as diluents. Binding power was evaluated on the basis of the granulometric shift and the rheological and mechanical characteristics of granules. [Rolim P et al; J Pharm Belg 47: 115-128 (Mar-Apr 1992)]**PEER REVIEWED**
  
• A study was made to determine the effect of Haemonchus contortus parasitic infection in lambs on the clearance of several IV administered drugs. Clearance of sulfobromophthalein or sulfathiazole from the plasma of lambs was unaffected by infection with H contortus. Clearance of antipyrine was enhanced by the infection, and thiabendazole treatment did not alter this effect. Clearance of chloramphenicol (CAP), administered as the succinate ester (CAPS), was not changed by the infection, but it was increased after treatment with thiabendazole. Changes in the mean body residence time and initial plasma concentration of chloramphenicol succinate ester and chloramphenicol after treatment with thiabendazole indicate that hydrolysis of chloramphenicol succinate ester to chloramphenicol was reduced. High concentrations of chloramphenicol succinate ester apparently enhanced its own elimination directly rather than via the expected sequence involving hydrolysis, glucuronidation, and excretion of chloramphenicol-glucuronide. Enhanced clearance of antipyrine following infection of lambs with H contortus can be explained in at least 2 ways. First, it is possible that the lambs did not have mature amounts of hepatic drug metabolizing enzyme activity as reported by other investigators, which may be explained by breed differences or animal husbandry practices. Second, infection of lambs by H contortus may have triggered an inductive response in hepatic cytochrome P-450-mediated activities, which might result via a generalized enhancement in hepatic protein synthesis associated with the physiologic response to replace plasma proteins and other blood components lost through gastrointestinal hemorrhage caused by the active feeding of adult worms. Other phase-II reactions such as acetylation, glucuronidation, and glutathione-S-transferase apparently were not affected. [Kawalek JC, Fetterer RH; Am J Vet Res 51 (12): 2044-9 (1990)]**PEER REVIEWED**
  
• The preparation and release characteristics of microcapsules of sulfathiazole prepared from an emulsion of gelatin and the triethylamine salt cellulose acetate phthalate are described. [Dittrich M, Melichar L; Cesk Farm 38: 214-218 (May 1989)]**PEER REVIEWED**
  
• Three modifications of the emulsion method of microencapsulation were tested for release and structural properties, using sulfathiazole (particle size 125 to 160 mcm) as the model drug and either gelatin (I), potassium celacephate (II), or a mixture of the 2 as the coating olymers. It was concluded that the 3 modifications described are suitable for the preparation of pharmaceutical microcapsules from a mixture of gelatin and potassium celacephate [Dittrich M et al; Cesk Farm 38: 401-406 (Sep 1989)]**PEER REVIEWED**
  
• The stability of sulfamethazine (sulfadimidine) sulfathiazole, sulfameter (sulfamethoxydiazine), and sulfacetamide during acid hydrolysis in one mol/l of hydrochloric acid under increased temperature was examined using high pressure liquid chromatography. Kinetic characteristics of the process of decomposition were calculated from the found values of the concentration of undecomposed sulfonamide in relation to time. The calculated values of activation energy for the individual sulfonamides are given. The paper stresses the illustrativeness of HPLC in the examination of decomposition products. [Klimes J,Zahradnicek M; Folia Pharm 11 (1): 41-55 (1988)]**PEER REVIEWED**
  
• The effect of surfactant on the properties of tablets of sulfanilamide and sulfathiazole containing microcrystalline cellulose and the mechanism by which microcrystalline cellulose influences disintegration and dissolution of tablets formulated with surfactants are described. With adequate solubility the surfactant promoted tablet disintegration through its surface activity by making the tablet matrix more readily wetted by depressing the surface tension. [Wan LS, Heng PW; Pharm Acta Helv 61 (5-6): 157-163 (1986)]**PEER REVIEWED**
  
• In vitro dissolution rates of sulfathiazole were measured following microencapsulation with ethylcellulose in varying ratios. A delay in dissolution was observed with the microcapsules, with a linear relationship between wall thickness and time to 50% dissolution. Thicker walls were found to yield slower release profiles. [Chowdhary KPR, Prasad Y; Indian J Pharm Sci 44: 61-62 (May-Jun 1982)]**PEER REVIEWED**
  
• Meerschaum, a Turkish magnesium trisilicate found in Eskisehir and its surroundings, was evaluated as a tableting excipient in preparing sulfathiazole (I) tablets. A sample containing 33.3% magnesium oxide and 51.1% silicon dioxide was powdered and the powder fraction with a particle size of 125-200 mum was used. By the addition of 20% of the excipient as a disintegrating agent, or by using 15% w/v as a binder, I tablets were prepared with good mechanical, disintegration and dissolution properties. [Bayraktar-Alpmen G; Istanbul Univ Eczacilik Fac Mecm 16 (1): 35-55 (1980)]**PEER REVIEWED**
  

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Metabolism/Metabolites

• SULFATHIAZOLE...IS ONE OF THE SHORT-ACTING SULFONAMIDES & IN MAN IS EXCRETED IN URINE AS UNCHANGED SULFATHIAZOLE (63% OF DOSE), N4-ACETYLSULFATHIAZOLE (29%), SULFATHIAZOLE-N4-GLUCURONIDE (0.8%), SULFATHIAZOLE-N4-SULFATE (0.5%) & SULFATHIAZOLE-N1-GLUCURONIDE (3.8%). [Parke, D. V. The Biochemistry of Foreign Compounds. Oxford: Pergamon Press, 1968., p. 180]**PEER REVIEWED**
  
• SULFONAMIDES UNDERGO METABOLIC ALTERATIONS TO VARYING EXTENT IN TISSUES, ESP IN LIVER. BOTH ACETYLATION & OXIDATION OCCUR. ... IN NEARLY ALL SPECIES, MAJOR METABOLIC DERIVATIVE IS N4-ACETYLATED SULFONAMIDE. /SULFONAMIDES/ [Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1059]**PEER REVIEWED**
  
• The antimicrobial agents may undergo a change in the complex stomach particularly in the rumen as a result of microbial fermentation in ruminants. Present investigation deals with the influence of ruminal fluid probably the role of ruminal microorganisms on the degradation of sulfathiazole in vitro and its metabolism and disposition following its single intraruminal administration (100 mg/kg) in adult german black head sheep. Sulfathiazole is metabolized to N4-acetyl sulfathiazole in the rumen fluid after its in vitro incubation at different concentrations (10-60 ug/ml) for varying time intervals (1-6 hr) at a temperature of 38 +/- 0.5 deg C. Likewise in vivo it is significantly metabolized to its N-acetyl metabolite in the rumen after an intraruminal administration. The levels of sulfathiazole are maintained above minimum effective therapeutic concentration (40 ug/ml) for more than 24 hr in rumen fluid. The drug is poorly absorbed into the circulation after intraruminal administration since the levels in plasma could not reach up to minimum effective therapeutic concentration at any time. The biological half-life of sulfathiazole was found to be 16.7 hr following single intraruminal administration. Results of this investigation suggest that oral or intraruminal application of sulfathiazole has only local effects in the rumen fluid. A systemic treatment is not possible after this path of application. [Jain SK, Hapke HJ; DTW Dtsch Tierarztl Wochenschr 102 (5): 193-5 (1995)]**PEER REVIEWED**
  
• (14)C-Sulfamethazine (4-amino-N-(4,6-dimethyl-2-pyrimidinyl)benzene-(U-14(C)-sulfonamide, 220 mg/kg of body weight) was given orally or iv to lactating dairy cows. Milk collected from 0-48 hr after dosing accounted for 2.0% (oral dose) and 1.1% (iv dose) of the total (14)C-activity administered. Sulfamethazine accounted for 70-79% (oral dose) and 54-75% (iv dose) of the total (14)C in milk samples collected from 0-48 hr after dosing. N4-acetylsulfamethazine accounted for 1-2% (oral dose) and 1-4% (iv dose) of the (14)C in milk. The major (14)C-labelled metabolite in the milk was isolated and identified as the N4-lactose conjugate of sulfamethazine, a unique type of metabolite not previously reported. This metabolite accounted for 10-14% (oral dose) and 9-20% (iv dose) of the (14)C-activity in the milk collected from 0-48 hr after dosing with (14)C-sulfamethazine. N4-lactose conjugates of sulfapyridine, sulfamerzine, sulfathiazole, sulfadimethoxine and sulfaquinoxaline were present in the milk from cows orally dosed with these five sulfonamide drugs. [Paulson GD et al; Xenobiotica 22 (8): 925-939 (1992)]**PEER REVIEWED**
  

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TSCA Test Submissions

• None found

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Footnotes

¹ Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.