2-DESOXY-2-(3-METHYL-3-NITROSOUREIDO)-D-글루코피라노스

Pharmaceuticals -> Antibiotics

Pharmaceuticals -> Listed in ZINC15

POINTED PLATELETS OR PRISMS FROM 95% ETHANOL

PALE-YELLOW CRYSTALS

Ivory-colored crystalline powder

Soluble (NTP, 1992)

SOL IN WATER, LOWER ALCOHOLS & KETONES.

SLIGHTLY SOL IN POLAR ORG SOLVENTS; INSOL IN NON-POLAR ORGANIC SOLVENTS.

3.35e+01 g/L

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

239 °F (Decomposes) (NTP, 1992)

115 °C

SPECIFIC OPTICAL ROTATION: +39 DEG @ 25 °C/D (AQ SOLN); MAX ABSORPTION (ALCOHOL): 228 NM (E= 6360).

OPTICAL ROTATION: AQ SOLN UNDERGO MUTAROTATION TO EQUIL VALUE OF +39 DEG @ 25 °C/D.

Streptozocin is an off-white powder. Melting point 115 °C. Used as an anti-cancer drug. Carcinogenic.

Ivory-colored or pale yellow solid; [HSDB] Light yellow crystalline solid; [MSDSonline]

Solid

DECOMPOSES TO DIAZOMETHANE IN ALKALINE SOLN @ 0 °C.

When stored as recommended, the powder for injection is stable for at least 3 years after the date of manufacture; when stored at room temperature, the powder for injection is stable for a least 1 year after the date of manufacture.

This chemical does not meet GHS hazard criteria for 1.8% (1 of 57) of reports.

Danger

H312 (22.8%): Harmful in contact with skin [Warning Acute toxicity, dermal]

P203, P261, P271, P280, P302+P352, P304+P340, P317, P318, P321, P362+P364, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 57 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

Emergency treatment: Symptomatic drug parenteral exposure; [HSDB] Causes diabetes mellitus and increase in liver enzymes in feeding studies of rats with a TDLo =55 mg/kg; [RTECS] Induces diabetes in animals, and diabetes affects pregnancy outcomes; [REPROTOX] May cause irritation; May be harmful by ingestion, inhalation, or skin absorption; Targets pancreas, liver, kidneys, blood, and reproductive system; [Aldrich MSDS]

Weisburger EK; Bioassay Program for Carcinogenic Hazards of Cancer Chemotherapeutic Agents; Cancer 40: 1935-49 (1977). Route: intraperitoneal injection; Species: rats and mice.

Newell D et al; N-methyl Antitumor Agents. A Distinct Class of Antitumor Drugs? Cancer Chemother Pharmacol 19 (2): 91-102 (1987). A review of structure-activity characteristics, mode of action, pharmacokinetics and clinical utility of a group of chemically dissimilar antitumor agents which have as a common structural feature the N-methyl moiety.

National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Streptozotocin (18883-66-4) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s163stre.pdf]

Wilson GL, Leiter EH; Streptozotocin Interactions with Pancreatic Deta Cells and the Induction of Insulin-dependent Diabetes Curr Top Microbiol Immunol 156: 27-54 (1990).

U206; As stipulated in 40 CFR 261.33, when streptozotocin, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 1 lb or 0.454 kg. The toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

Commercially available streptozotocin powder for injection should be protected from light and stored at 2-8 °C.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U206, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids. A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for STREPTOZOTOCIN (7 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for STREPTOZOTOCIN (9 total), please visit the HSDB record page.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

EXPERIMENTALLY ... SHOWN ... THAT DIABETES INDUCED IN RATS BY ... STREPTOZOTOCIN ENHANCES HEPATOTOXICITY OF CARBON TETRACHLORIDE. REVERSAL OF DIABETIC STATE BY INSULIN TREATMENT PREVENTED THE POTENTIATED RESPONSE.

Male Wistar rats were divided into six groups. For inducing diabetes, a single iv injection of 60 mg streptozotocin/kg in a physiological saline solution was given at the time indicated below. Manganese was given by ip injection of 15 mg manganese chloride/kg/day in the saline solution for a period indicated in each group. Group 1 was injected with a vehicle for streptozotocin and saline solution for 2 wk (control group). Group 2 was given streptozotocin and treated with saline for 2 wk (streptozotocin group). Group 3 was given the vehicle for streptozotocin and saline for 1 wk, then received manganese for 2 wk (saline-manganese group). Group 4 was injected with streptozotocin and later treated in the same way as in group 3 (streptozotocin-manganese group). Group 5 was administered with managanese for 2 wk, given streptozotocin and followed by 1 wk saline administration (manganese-streptozotocin-saline group). Group 6 was also given manganese for 2 wk and streptozotocin but followed by manganese for 1 wk (manganese-streptozotocin-manganese group). When streptozotocin was given, the blood glucose level rose over 400 mg/dl and stabilized in a few days. The manganese content in the pancreas, spleen, and kidney of streptozotocin-manganese-treated rats were much lower than those in the tissues in group 3, whereas, those in the brain, thymus, and liver remained unchanged. The pancreas, kidney, and brain of group 6 showed more of an incr in manganese content than did those in the manganese-streptozotocin-saline group (group 5). The liver showed a slight incr in manganese content, but the thymus and spleen of group 6 had less manganese contents than did those of group 5.

In rats, the development of cataracts /by streptozotocin/ were interfered with by administering nicotinamide, a unsaturated fat diet, vitamin E, or aldose- reductase inhibitors.

Concurrent administration of streptozocin with carmustine profoundly enhanced marrow toxicity and the incidence of thrombocytopenia; therapeutic activity was not enhanced.

For more Interactions (Complete) data for STREPTOZOTOCIN (16 total), please visit the HSDB record page.

Serum aminotransferase elevations occur in up to two-thirds of patients treated with streptozocin, but the abnormalities are generally mild, transient and not associated with symptoms or jaundice. Hepatotoxicity is more common with daily dosing and high doses of streptozocin, but with higher doses renal and hematologic toxicities usually overshadow hepatic injury. There have been two reports of rapidly progressive and fatal acute liver failure in patients treated with streptozocin. In one instance, no other chemotherapy was given, in another fluorouracil was coadministered and the patient presented with fever, anuria, acute hepatitis [ALT 1280, bilirubin 11.9, prothrombin index 10%, eosinophils 2600/ µL] at the end of a 5 day course of treatment. In contrast, there have been no individual published case reports of self-limited clinically apparent liver injury attributed to streptozocin, but it has had limited use, as pancreatic islet cell carcinoma and neuroendocrine tumors are rare.

Streptozotocin is a naturally occurring chemical that is particularly toxic to the insulin-producing beta cells of the pancreas. It is used in medical research to produce an animal model for Type 1 diabetes in large dose as well as Type 2 diabetes with multiple low doses. Streptozotocin is similar enough to glucose to be transported into the cell by the glucose transport protein GLUT2, but is not recognized by the other glucose transporters. This explains its relative toxicity to beta cells, since these cells have relatively high levels of GLUT2. Streptozotocin is a glucosamine-nitrosourea (i.e. alkylating) compound. As with other alkylating agents in the nitrosourea class, it is toxic to cells by causing damage to the DNA, though other mechanisms may also contribute.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=18883-66-4]

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

Renal dysfunction is the major dose-limiting toxicity and occurs in 26% to 73% of patients. The drug is toxic to both renal tubules and glomeruli.

... NOTED NAUSEA & VOMITING IN ALMOST ALL OF 52 PATIENTS TREATED FOR ISLET-CELL CARCINOMA. RENAL OR HEPATIC TOXICITY OCCURS IN APPROX TWO THIRDS OF CASES; ALTHOUGH USUALLY REVERSIBLE RENAL TOXICITY MAY BE FATAL, & PROXIMAL TUBULAR DAMAGE IS THE MOST IMPORTANT EFFECT.

HEMATOLOGICAL TOXICITY, CONSISTING OF ANEMIA, LEUKOPENIA, OR THROMBOCYTOPENIA OCCURS IN 20% OF PATIENTS.

Streptozotocin is potentially carcinogenic in humans. ... Atypia of cells lining the alveoli, pancreatic acinar cells, hepatocytes, hepatobiliary ductules, and regenerating proximal renal tubular cells has reportedly developed in patients who received streptozotocin for the treatment of pancreatic neoplasms. Multiple spindle cell tumors in the renal cortex have also been reported in one patient receiving the drug. ... Renal tubular squamous metaplasia reportedly developed in one patient following treatment with streptozocin for metastatic islet cell carcinoma of the pancreas. Acute leukemia also reportedly developed in one patient approximately 1 year after discontinuance of prolonged streptozocin therapy for the treatment of metastatic islet cell carcinoma of the pancreas.

Uric acid nephrolithiasis developed in a 75 yr old man who had received a large cumulative dose of streptozotocin for treatment of metastatic islet cell carcinoma of the pancreas. Oligoanuric renal failure mediated by massive intraureteral uric acid deposits occurred despite normal serum concentrations of uric acid. This case implicates the uricosuric effects of streptozotocin in the pathogenesis of uric acid nephropathy and suggests that renal uric acid excretion should be monitored routinely in patients receiving large cumulative doses of this drug.

Streptozotocin

Group 2B: Possibly carcinogenic to humans

Volume 17: (1978) Some N-Nitroso Compounds

1987

1987

2B, possibly carcinogenic to humans. (L135)

U206; As stipulated in 40 CFR 261.33, when streptozotocin, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 1 lb or 0.454 kg. The toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

Streptozocin is an antitumour antibiotic consisting of a nitrosourea moiety interposed between a methyl group and a glucosamine. Streptozocin is indicated in the treatment of metastatic islet cell carcinoma of the pancreas. Streptozocin inhibits DNA synthesis in bacterial and mammalian cells. In bacterial cells, a specific interaction with cytosine moieties leads to degradation of DNA. The biochemical mechanism leading to mammalian cell death has not been definitely established; streptozocin inhibits cell proliferation at a considerably lower level than that needed to inhibit precursor incorporation into DNA or to inhibit several of the enzymes involved in DNA synthesis. Although streptozocin inhibits the progression of cells into mitosis, no specific phase of the cell cycle is particularly sensitive to its lethal effects.

Although its mechanism of action is not completely clear, streptozocin is known to inhibit DNA synthesis, interfere with biochemical reactions of NAD and NADH, and inhibit some enzymes involved in gluconeogenesis. Its activity appears to occur as a result of formation of methylcarbonium ions, which alkylate or bind with many intracellular molecular structures including nucleic acids. Its cytotoxic action is probably due to cross-linking of strands of DNA, resulting in inhibition of DNA synthesis.

DRUG IS CAPABLE OF INHIBITING SYNTH OF DNA IN MICROORGANISMS & MAMMALIAN CELLS; IT AFFECTS ALL STAGES OF MAMMALIAN CELL CYCLE. BIOCHEMICAL STUDIES HAVE ALSO REVEALED POTENT INHIBITORY EFFECTS ON PYRIDINE NUCLEOTIDES & ON KEY ENZYMES INVOLVED IN GLYCONEOGENESIS.

Mechanisms underlying cytotoxicity by the monofunctional nitrosourea streptozotocin were evaluated in DNA repair-deficient E coli mutants. Strains not proficient in recombinational repair which lack either RecA protein or RecBC gene products were highly sensitive to streptozotocin (1X10-4 to 1X10-6 M concn for 30 min at 37 °C). In contrast, cells that constituitively synthesize RecA protein and cannot initiate SOS repair mechanisms because of uncleavable LexA repressor (recAo98 lexA3) were resistant to this drug compared to a lexA3 strain. E coli cells lacking both 3-methyladenine DNA glycosylases I (tag) and II (alkA) also were highly sensitive to streptozotocin. DNA synthesis was most inhibited by streptozotocin in recA and alkA tag E coli mutants, but was suppressed less markedly in wild-type and recBC cells. DNA degradation was most extensive in recA E coli after streptozotocin treatment (400 ul 10-3 M for 30 min at 37 °C), while comparable in recBC, alkA tag, and wild-type cells. Although incr single-stranded DNA breaks were present after streptozotocin treatment in recA and recBC mutants compared to the wild type, no significant incr in DNA single-stranded breaks was noted in alkA tag E coli. Further, DNA breaks in recBC cells were repaired, while those present in recA cells were not.

5-15 minutes

AFTER IV INFUSIONS OF 200-1600 MG/SQ M, PEAK CONCN IN PLASMA ARE 30-40 UG/ML; HALF-LIFE OF DRUG IS APPROX 15 MIN. ONLY 10-20% OF DOSE IS RECOVERED IN URINE.

... STREPTOZOTOCIN ... FOLLOW APPARENT TWO-COMPARTMENT MODEL KINETICS IN MAN AFTER BOLUS IV INJECTION, WITH MEAN FAST & SLOW DISPOSITION HALF-TIME VALUES OF 4.6 & 40 MIN RESPECTIVELY. THE LATTER VALUE IS 2.5-FOLD GREATER THAN REPORTED PREVIOUSLY FOR PT RECEIVING STREPTOZOTOCIN BY SLOW IV INFUSION.

SEVEN PATIENTS GIVEN SINGLE 1.5 G/SQ M IV DOSE SHOWED MEAN HALF-LIFE OF APPROX 40 MINUTES & HALF-LIFE OF ELIMINATION OF ABOUT 15 MINUTES.

Primarily hepatic

STUDIES WITH STREPTOZOTOCIN LABELLED WITH (14)C IN DIFFERENT POSITIONS INDICATE THAT ITS RAPID METABOLISM IN RAT ... RESULTS IN METABOLITE DERIVED FROM METHYL BEARING NITROSOUREIDO SIDECHAIN. /SRP: DIAZOMETHANE/

/IN MICE URINE/ FIVE URINARY METABOLITES WERE DETECTED; 2 OF THEM WERE THE ALPHA AND BETA-ANOMERS OF THE ANTIBIOTIC.

Streptozocin and metabolites have a short distribution phase (t1/2 6 min) followed by possibly two elimination phases representing active metabolites (t1/2 beta 3.5 hr, t1/2 gamma 40 hr).

Streptozocin is not orally active. After intravenous administration, it is rapidly cleared from plasma and is undetectable after three hours. Metabolites are detected in plasma for up to 24 hours. The drug concentrates in certain tissues; the liver and kidneys contain the highest levels, and pancreas also concentrates streptozocin. Parent drug and metabolites are eliminated rapidly by the kidney; 60% to 70% of a dose is recovered in urine within four hours. Only 10% to 20% of an excreted dose is parent drug.

Primarily hepatic Route of Elimination: As much as 20% of the drug (or metabolites containing an N-nitrosourea group) is metabolized and/or excreted by the kidney. Half Life: 5-15 minutes

5W494URQ81

STREPTOZOCIN

Mechanisms of Action [MoA] - Alkylating Activity

Established Pharmacologic Class [EPC] - Alkylating Drug

Streptozocin is an Alkylating Drug. The mechanism of action of streptozocin is as an Alkylating Activity.

STREPTOZOCIN

Poor oral absorption (17-25%)

As much as 20% of the drug (or metabolites containing an N-nitrosourea group) is metabolized and/or excreted by the kidney.

IN ALL THESE SPECIES /MICE, RATS, CATS, MONKEYS & DOGS/ STR /STREPTOZOTOCIN/ GIVEN PARENTERALLY ... MARKEDLY CONCENTRATED IN LIVER & KIDNEY; FOR EXAMPLE, IN DOGS ... RETAINED IN LIVER FOR MANY HR AFTER ... NO LONGER ... DETECTED IN BLOOD .

STREPTOZOTOCIN ... WELL ABSORBED FROM GI TRACT IN MICE, BUT ABSORPTION WAS POOR IN MONKEYS & NEGLIGIBLE IN DOGS.

(14)C-LABELLED STREPTOZOTOCIN GIVEN BY IV INJECTION WAS RAPIDLY CLEARED FROM BLOOD OF RATS, SO THAT LESS THAN 1% REMAINED AFTER 10 MINUTES.

STREPTOZOTOCIN (NSC-85998) WAS RAPIDLY EXCRETED IN URINE OF TREATED MICE; 72% OF AN INJECTED DOSE IN THE 4-HR URINE. FIVE URINARY METABOLITES WERE DETECTED ... .

Produced by Streptomyces achromogenas (soil microorganisms); Used to produce diabetes in experimental animals and as an antineoplastic agent; [HSDB]

EMPLOYED AS DIABETOGENIC AGENT IN EXPERIMENTAL ANIMALS.

PRODUCTION OF EXPTL DIABETES IN LAB ANIMALS; ANTINEOPLASTIC.

MEDICATION

MEDICATION (VET)

For the treatment of malignant neoplasms of pancreas (metastatic islet cell carcinoma).

(1977) PROBABLY GREATER THAN 9.08X10+5 GRAMS

(1979) PROBABLY GREATER THAN 9.08X10+5 GRAMS

PURIFICATION FROM STREPTOMYCES ACHROMOGENES CULTURES; SYNTHESIS FROM TETRA-O-ACETYL GLUCOSAMINE HYDROCHLORIDE; REACTION OF D-GLUCOSAMINE WITH N-NITROSOMETHYLCARBAMYLAZIDE OR N-METHYLISOCYANATE.

ISOLATION FROM STREPTOMYCES ACHROMOGENES FERMENTATION BROTH.

Streptozotocin is available in 1 g vials as a powder for injection.

Commercially available streptozocin for injection occurs as a sterile, pale yellow, lyophilized powder and contains anhydrous citric acid as a buffer; sodium hydroxide is added during manufacture of the powder for injection to adjust pH.