Huagongshe화공사 화학 정보 인쇄 보고서 · 연구 참고용
피리미돈
프리미돈 · 피리미돈 · Primidon · Cyral · Midone · roe101 · Sertan · Mizodin
식별자 및 물리적 특성
| CAS No. | 125-33-7 |
|---|---|
| 분자식 | C12H14N2O2 |
| 평균 분자량 | 218.25 g/mol |
| 단동위원소 질량 | 218.10552769 g/mol |
| SMILES | CCC1(c2ccccc2)C(=O)NCNC1=O |
| InChIKey | DQMZLTXERSFNPB-UHFFFAOYSA-N |
| PubChem CID | 4909 |
| ChEMBL | CHEMBL856 |
| ChEBI | CHEBI:8412 |
| EC No. | 204-737-0 |
| DTXSID | DTXSID7023510 |
| 현지명 | 피리미돈 |
화학 및 물리적 성질
| XLogP | 0.9 |
|---|---|
| 극성 표면적 | 58.2 |
| 수소 결합 공여자 수 | 2 |
| 수소 결합 수용자 수 | 2 |
| 회전 가능 결합 수 | 2 |
| 무거운 원자 수 | 16 |
| 형식 전하 | 0 |
| 복잡도 | 279 |
| 의약품 | Pharmaceuticals -> Used in SwitzerlandPharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Antiepileptic |
| pH | Has no acidic properties |
| LogP(분배 계수) | log Kow = 0.911.6 |
| 냄새 | Odorless |
| 맛 | Practically tastelessSlightly bitter taste |
| Color/Form | CrystalsWhite crystalline powder |
| 용해도 | less than 1 mg/mL at 66 °F (NTP, 1992)In water, 480 mg/L at 30 °CVery slightly soluble in waterVery slightly soluble in most organic solvents1.04e+00 g/L물에는 매우 약간 용해되고, 에탄올에는 약간 용해됩니다(96%). 알칼리성 용액에 용해됩니다. |
| Human Drugs | Breast FeedingLactationMilk, HumanAnticonvulsantsBarbituratesFDA approved drugs -> Active ingredientPharmaceuticals |
| Animal Drugs | FDA approved animal drugs -> Active ingredient |
| Decomposition | When heated to decomposition it emits toxic fumes of /nitrogen oxides/. |
| 녹는점 | 538 to 540 °F (NTP, 1992)281.5 °CMP: 281-282 °C281-282°C |
| Physical Description | Primaclone is an odorless white crystalline powder. Slightly bitter taste. No acidic properties. (NTP, 1992)Solid |
| 끓는 점 | 358.94°C (rough estimate) |
| 밀도 | 1.1402 (rough estimate) |
| 굴절률 | 1.6660 (estimate) |
| 인화점 | 9℃ |
| 저장 조건 | Sealed in dry,Room Temperature |
| pKa(산도 계수) | 12.26±0.40(Predicted) |
| 물리적 상태 | Solid |
| 색상 | 흰색에서 황백색까지 |
| 용해도 | 19ºC에서 <0.1g/100mL |
| Merck | 14,7746 |
| BCS Class | 2 |
| 주요 응용 | 법의학 및 독성학의약품(소분자)수의사 |
| InChI | 1S/C12H14N2O2/c1-2-12(9-6-4-3-5-7-9)10(15)13-8-14-11(12)16/h3-7H,2,8H2,1H3,(H,13,15)(H,14,16) |
| InChIKey | DQMZLTXERSFNPB-UHFFFAOYSA-N |
| SMILES | CCC1(C(=O)NCNC1=O)c2ccccc2 |
| NIST | Primidone(125-33-7) |
| EPA | Primidone (125-33-7) |
화학적 성질
Crystalline Solid
안전 및 규제
| GHS 분류 | DangerH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P264, P270, P280, P301+P317, P318, P330, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 49 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.H302: Harmful if swallowed [Warning Acute toxicity, oral] |
|---|---|
| 규제 정보 | Hazard Traits - CarcinogenicityPrimidone: Does not have an individual approval but may be used under an appropriate group standard |
| 기타 안전 정보 | IMAP assessments - 4,6(1H,5H)-Pyrimidinedione, 5-ethyldihydro-5-phenyl-: Environment tier I assessment |
| 운송 라벨(DOT) | Poison |
| 화재 위험 | Flash point data for this chemical are not availablehowever, it is probably combustible. (NTP, 1992) |
| 건강 유해성 | SYMPTOMS: Symptoms of exposure to this compound via ingestion may include sleepiness, mental confusion, unsteadiness, coma, slow and shallow respiration flaccid muscles, hypotension, cyanosis, hypothermia or hyperthermia, absent reflexes, painful gums and excessive fatigue. Other symptoms of exposure through ingestion may include ataxia, vertigo, nausea, anorexia, vomiting, hyperirritability, emotional disturbances, sexual impotency, diplopia, nystagmus, morbilliform skin eruptions and possible megaloblastic anemia. Ingestion may also lead to sedation, dizziness, an acute feeling of intoxication, maculopapular rash, leukopenia, thrombocytopenia, systemic lupus erythematosus, lymphadenopathy, acute psychotic reactions, hemorrhagic disease in the neonate and osteomalacia. It can cause mental dullness, drooping of the eyelids and, rarely, blurred and narrow vision. It can also cause a coma, the duration of which is dependent on the dose. If the coma continues, moist rales are heard in the lower lung fields, indicating pulmonary edema. Atelectasis or aspiration pneumonia with signs of lung consolidation and fever can also occur. Carbon dioxide retention under these conditions causes acidosis. Death occurs most often from pneumonia, pulmonary edema or refractory hypotension. Cerebral edema contributes to the persistence of coma. Chronic symptoms of ingestion include skin rash, mental confusion, drowsiness, hangover, emotional lability or depression, irritability, poor judgment, neglect of personal appearance and other behavior disturbances. Other symptoms may include general malaise, polyuria, thyroid enlargement, epidermal necrolysis, tremors, central nervous system depression, disequilibrium, personality changes, thirst and impaired sexual function. |
| FDA 요건 | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including primidone, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Primidone is included on this list.Oral dosage form new animal drugs. Primidone. ... Indications for use. For the control of convulsions associated with idiopathic epilepsy, epileptiform convulsions, viral encephalitis, distemper, and hardpad disease that occurs as a clinically recognizable lesion in certain entities in dogs. ... Limitations. Federal law restricts this drug to use by or on the order of a licensed veterinarian. |
| 반응성 그룹 | Amides and Imides |
| Special Reports | Brodie MJ, Dichter MAN Engl J Med 334: 168-75 (1996). A review of the practical management of epilepsy with established antiepileptic drugs is /presented/.Dessens AB, et alActa Paediatr Suppl 404: 54-64 (1994). Studies on long lasting consequences of prenatal exposure to anticonvulsant drugs.Pranzatelli MR, Nadi NSAdv Neurol 67: 329-60 (1995). Mechanism of action of antiepileptic drugs and antimyoclonic drugs.Pacifici GM, Nottoli RClin Pharm 28 (3): 235-69 (1995). Placental transfer of drugs administered to the mother.For more Special Reports (Complete) data for Primidone (8 total), please visit the HSDB record page. |
| Reactivity Profile | PRIMACLONE is an amide. May react with azo and diazo compounds to generate toxic gases. May react with strong reducing agents to form flammable gases. A very weak base. The Combustion generates toxic mixed oxides of nitrogen (NOx). |
| Air and Water Reactions | Insoluble in water. |
| Toxic Combustion Products | Special hazards arising from the substance or mixture: Carbon oxides, nitrogen oxides (NOx). |
| Hazard Classes and Categories | Acute Tox. 4 (100%) |
| 소화 | Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992) |
| 응급 처치 | 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. If symptoms (such as redness or irritation) develop, immediately transport the victim to a hospital. |
| 소화 절차 | Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary. |
| 보관 조건 | 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/Keep container tightly closed in a dry and well-ventilated place.Primidone tablets should be stored in well-closed containers at a temperature less than 40 °C, preferably at 15-30 °C. |
| 정리 방법 | 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/ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. |
| 비화재 누출 대응 | SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. |
| 처리 방법 | SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.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/PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/For more Disposal Methods (Complete) data for Primidone (7 total), please visit the HSDB record page. |
| Preventive Measures | 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 Primidone (14 total), please visit the HSDB record page. |
| Isolation and Evacuation | Excerpt from ERG Guide 151 [Substances - Toxic (Non-Combustible)]: |
| Personal Protective Equipment (PPE) | RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist 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/Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).Skin protection: Handle with gloves.Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). |
| 상호 작용 | When acetaminophen in therapeutic doses is used concurrently in patients receiving chronic primidone therapy, its effects may be decreased because of increased metabolism resulting from induction of hepatic microsomal enzymes by the phenobarbital metabolitealso, risk of hepatotoxicity with single toxic doses or prolonged use of acetaminophen may be increased in chronic alcoholics or in patients regularly using hepatic-enzyme inducing agents.Concurrent use of adrenocorticoids, glucocorticoid and mineralocorticoidcoumarin- or indandione-derivative anticoagulantstricyclic antidepressantschloramphenicoloral estrogen-containing contraceptivescorticotropin (ACTH)cyclosporinedacarbazinedigitalis glycosides, with possible exception of digoxindisopyramidedoxycyclinelevothyroxinemetronidazolemexiletineor quinidine with primidone may decrease the effects of these medications because of increased metabolism resulting from induction of hepatic microsomal enzymes by the barbiturate metabolite. Dosage increases may be necessary during and after primidone therapy. Use of nonhormonal method of birth control or a progestin-only oral contraceptive may be necessary during primidone therapy. Also, concurrent use of tricyclic antidepressants with primidone may enhance CNS depression, lower convulsive threshold, and decrease the effects of primidonedosage adjustments may be necessary to control seizures.Concurrent use of alcohol or CNS depression-producing medications may potentiate the CNS and respiratory depressant effects of either these medications or primidonedosage adjustment of primidone may be necessary.Concurrent use of amphetamines may cause a delay in the intestinal absorption of the phenobarbital metabolite.For more Interactions (Complete) data for Primidone (21 total), please visit the HSDB record page. |
| Hepatotoxicity | In clinical trials in epilepsy, therapy with primidone was not associated with an increased frequency of serum aminotransferase elevations or liver toxicity. Primidone therapy can lead to increases in gamma glutamyltranspeptidase (GGT) levels. Elevations in alkaline phosphatase levels were largely due to bone isoforms of the enzyme. There have been no convincing reports of hepatotoxicity due to primidone in humans and no reports of its association with acute liver failure. Interestingly, primidone appears to cause cirrhosis in dogs. Because of its similarity in structure to phenytoin and phenobarbital (aromatic anticonvulsant), it has been suspected to cross react with those agents in causing anticonvulsant hypersensitivity syndrome, but convincing case reports have not been published. |
| 환경 거동 | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 140(SRC), determined from a structure estimation method(2), indicates that primidone is expected to have high mobility in soil(SRC). Volatilization of primidone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.9X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). Primidone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.3X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2018).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 140(SRC), determined from a structure estimation method(2), indicates that primidone is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.9X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). According to a classification scheme(4), an estimated BCF of 3(SRC), from its log Kow of 0.91(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2018).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), primidone, which has an estimated vapor pressure of 3.3X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase primidone may be removed from the air by wet and dry deposition(SRC). Primidone does not contain chromophores that absorb at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC). |
| 유해 작용 | The most common adverse effects of primidone therapy are sedation and drowsiness. Ataxia, diplopia, and nystagmus occur at the initiation of treatment. Other adverse reactions include dizziness, vertigo, epigastric pain, megaloblastic anemia, respiratory depression, polyuria, skin rash, and facial edema. Hypersensitivity reactions tend to occur more frequently in patients with a history of asthma, urticaria, or angioedema. Agranulocytosis and thrombocytopenia are rare. |
| Milk Concentrations | Primidone is distributed into breast milk in substantial amounts, and the use of primidone by nursing mothers may cause unusual drowsiness in the neonate. |
| 독성 요약 | IDENTIFICATION AND USE: Primidone is anticonvulsant, which is used alone or concomitantly with other anticonvulsants. It is indicated in the control of grand mal, psychomotor, and focal epileptic seizures. Primidone can be used for seizure control in dogs. HUMAN STUDIES: Overdosage of primidone results in symptoms similar to those of acute barbiturate intoxication. In addition, primidone crystalluria may occur and may facilitate the diagnosis. A case was reported of a patient who developed megaloblastic anemia caused by folate deficiency during treatment with primidone. In one study, children of epileptic women on medication with primidone were of lower weight and had smaller heads than children from epileptic mothers without medication and children from parents without epilepsy. Fetal exposure to primidone was associated with Goldenhar syndrome, hemifacial microsomia, tetralogy of Fallot, aqueductal stenosis, and anterior encephalocele in male infant. There is a report of the acardiac acephalic fetus of an epileptic mother who was on primidone therapy. In vitro studies showed no chromosomal aberration in human lymphocytes. ANIMAL STUDIES: Primidone caused a significant increase in the incidence of follicular cell adenoma of the thyroid in male rats. There was a small but significant increase in the incidence of renal tubule adenoma or carcinoma. The incidence of renal tubule hyperplasia was also increased in all groups of males receiving primidone. There was no significant increase in the incidence of any neoplasm in females. In mice, primidone caused significant increases in the incidence of hepatocellular adenoma, of hepatocellular carcinoma, and of hepatocellular adenoma, hepatocellular carcinoma, and hepatoblastoma (combined) in all dosed groups of males and females compared with controls. Primidone caused significant increases in the incidence of hepatoblastoma in all dosed groups of males. In males, there was also a significant positive trend in the incidence of follicular cell adenoma of the thyroid in mice receiving pyrimidone. There was an increased incidence in follicular cell hyperplasia of the thyroid in males and females receiving primidone. In pregnant rats treated with primidone the findings were consistent with the neurobehavioral teratology of phenobarbital, including its ability to produce lesions in the hippocampus and endocrine dysfunction resulting in reproductive deficits. These results suggest that primidone produced its adverse effects as a result of its metabolism to phenobarbital, which in turn affects the limbic system. Primidone was tested in as many as 5 Salmonella typhimurium strains (TA1535, TA1537, TA97, TA98, and TA100) in the presence and absence of metabolic activation. The compound was positive in strain TA1535 without activation. Because primidone is rapidly metabolized to phenobarbital in dogs, similar clinical signs (sedation to coma, anorexia, vomiting, nystagmus) are seen and corresponding procedures should be used for the treatment of acute primidone overdose.Primidone toxicity has been studied in numerous animal species and was found to be exceptionally low. Toxic levels are >15 μg/mL. Nevertheless, hepatotoxicity and behavioral problems with primidone are more common than phenobarbital. The ALT and ALP serum levels are more elevated for patients undergoing chronic primidone therapy than for any other widely used anticonvulsant. Additionally, there is documentation that hepatic cirrhosis secondary to chronic primidone use may also occur. Idiosyncratic reactions to primidone may also occur, which include hepatotoxicity and megaloblastic anemia. Dosing adjustments should be according to clinical response and biological monitoring in patients with renal impairment. |
| Ongoing Test Status | The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for primidone is available.[Available from, as of February 1, 2019: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPAICSS Dashboard ApplicationAvailable from, as of February 4, 2019: http://actor.epa.gov/dashboard/] |
| Effluent Concentrations | A concentration range of 11-130 ug/L was reported for primidone in Lake Mead waste water samples, USA, sampled in 2001(1). Concentrations of primidone in wastewater influent during and after a major US sporting event in 2011 were 68 and 42 g/day, respectively. Respective estimated effluent concentrations were 51 and 112 g/day(2). Primidone exhibited a removal rate range of -8 to 20% in an urban sewage treatment plant in Dresdin Germany, sampled for 10 consecutive days in January/February, 2015(3). Removal of primidone in wastewater treatment is minimal(4). Using wastewater samples from nine municipal wastewater treatment plants in the area of Zurich, Switzerland, mean primidone concentrations in influent and effluent were 0.17 and 0.18 ug/L, respectively(4). The compound was reported at mean concentrations of 122, 148 and 149 ng/L in effluent from a tertiary wastewater treatment facility in Los Angeles, CA sampled in July 2008, May 2009, and October 2009, respectively(5). Concentrations of 10.8 and 18-30 ng/L were reported in industrial waste water and sewage water, respectively, from The Netherlands in 2002(6). Primidone was present at a mean concentration of 2.5 ng/L in effluent discharged from nine wastewater treatment plants into the Han River, Seoul, South Korea, sampled on Sept 30, 2008(6). |
| Medical Surveillance | 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/ |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of primidone can be estimated to be 140(SRC). According to a classification scheme(2), this estimated Koc value suggests that primidone is expected to have high mobility in soil(SRC). Using a water/sediment matrix from the Elbe River, in Dresden, Germany and a flow-through column, primidone was shown to be very mobile with a log Koc of about 1.2 over pH range of 4 to 8(3). Primidone, present in recycled waste water at a range of 18-53 ng/L, was frequently discovered in leachate water at mean concentrations of 8.5 and 2.0 ng/L following application of recycled treated wastewater to turfgrass, (hybrid Bermida grass) underlaid with sandy loam or loamy sand soils, respectively, over a 6-month period(4). A pKa of 12.3 (acidic character of ionizable functional group) has been reported. In sediment column studies using sediment from an Elbe River tributary (Torgue, Germany) and flow water from the Elbe (Dresden), low retardation was observed and no pH dependence was reported. It was postulated that deprotonation of hydroxyl group due to lactam-lactim tautomerization cannot occur at pH 4 to 6 and, therefore, the molecule stays in neutral form and is very mobile because of its low Kow(5). |
| Human Toxicity Excerpts | /SIGNS AND SYMPTOMS/ Overdosage of primidone results in symptoms similar to those of acute barbiturate intoxication. In addition, primidone crystalluria may occur and may facilitate the diagnosis./CASE REPORTS/ The present paper describes a patient who was in danger of dying from a massive primidone overdose. She was comatose, hypotensive and in acute renal failure with crystalluria. Because of her clinical condition and high plasma primidone level (209 mg/L) hemoperfusion was instituted. Both the calculated drug clearances and the remarkable improvement in the patient's clinical condition suggest that hemoperfusion was very effective./CASE REPORTS/ Seven cases of crystalluria following primidone overdose have been reported since the 1950s. An eighth case of primidone crystalluria following overdose is presented. Because of low aqueous solubility (600 mg/L at 37 degrees C) which is directly proportional to temperature, any factor increasing renal excretion of unchanged primidone predisposes to crystal formation. Renal clearance is dependent on dosage because of negligible protein binding, zero-order conversion to phenobarbitone (phenobarbital) and first-order conversion to phenylethylmalonamide. Therapy with other anticonvulsants known to induce the metabolism to phenobarbitone does not appear to be protective against crystalluria in overdose situations. The critical serum primidone concentration for crystalluria presence seems to be 80 mg/L. There is evidence for nephrotoxicity of the crystals themselves if formed in vivo (actual crystal presence during voiding). The chemical phenomenon of supersaturation of a solution is protective against in vivo crystal formation with subsequent nephrotoxicity. Vigorous hydration to augment elimination and to lessen the propensity for renal toxicity is recommended./CASE REPORTS/ A 7.5-year-old girl who was treated with phenobarbital (PHB) for epilepsy was admitted with decreased levels of consciousness. She had been known to have high PHB levels of unknown cause, without symptoms. Her PHB levels were very high, as expected, but primidone levels were also detected although she and her parents denied history of primidone administration. We wished to rule out intentional unprescribed use of primidone. Our retrospective review showed 3 other children with high PHB concentrations where primidone was also detected when PHB levels were over 130 umol/L. Complementary studies confirmed that high-dose PHB can convert to its prodrug primidone, which has not been reported previously.For more Human Toxicity Excerpts (Complete) data for Primidone (16 total), please visit the HSDB record page. |
| Artificial Pollution Sources | Primidone's production and administration as an anticonvulsant in human and veterinary medicine(1) may result in its release to the environment through various waste streams(SRC). |
| 수질 위해 등급(WGK) | 3 |
| RTECS 번호 | UV9100000 |
| 운송 번호(UN) | 3249 |
| 독성 | child,TDLo,oral,625mg/kg (625mg/kg),BEHAVIORAL: SLEEPBEHAVIORAL: CHANGES IN MOTOR ACTIVITY (SPECIFIC ASSAY)BEHAVIORAL: GENERAL ANESTHETIC,British Medical Journal. Vol. 1, Pg. 90, 1957. |
| 관세 코드 | 29335990 |
| 위험 문구(R) | 22-40-39/23/24/25-23/24/25-11 |
| 위험 표시 | Xn,T,F |
| 안전 문구(S) | 22-36-45-36/37-16-7 |
| 포장분류 | III |
| 위험 등급 | 6.1(b)Acute Tox. 4 OralCarc. 2Repr. 2 |
| 기존화학 물질 | KE-13609 |
| 저장 분류 | 11 - Combustible Solids |
| 유해 물질 데이터 | 125-33-7(Hazardous Substances Data) |
용도
개요
Primidone is chemically and structurally similar to phenobarbital with the exception that the carbonyl group on C2 is replaced by a methylene group. This modification leads to the production of a drug with strong anticonvulsant properties without expressed soporific effects.
용도
Primidone is mainly used for major attacks.
일반 설명
Odorless white crystalline powder. Slightly bitter taste. No acidic properties.