Potassium bromide appears as odorless colorless crystals or white crystalline powder or white granular solid with a pungent bitter saline taste. Aqueous solutions are neutral (pH about 7). (NTP, 1992)
IDENTIFICATION AND USE: Potassium bromide is a solid. Potassium bromide may be utilized for the production of photographic-grade silver bromide, in process engraving, and lithography. Other uses for potassium bromide are in clear completion fluids in the petroleum industry, as a pharmaceutical intermediate, and in the manufacture of fibers. It has been used therapeutically in human and veterinary medicine. HUMAN STUDIES: A 3-year-old girl experienced bromoderma tuberosum following potassium bromide treatment for epilepsy. The symptoms disappeared after reduction of the bromide dose. Two iodine-sensitive women in whom potassium bromide solution was used as a radiocontrast agent for retrograde pyelography developed similar clinical conditions culminating in renal failure. Renal failure was due to upper urinary tract obstruction from fibrosis and fat necrosis in each case. Ingestion of potassium bromide at 12-50 g/man (8 cases) caused vomiting, diarrhea, gastritis, anuria, acute nephrosis, uremia, degeneration of neurons and proximal tubules of kidney, fatty degeneration of kidney and liver, edema in brain and kidney, hemolysis, then death 5 days later. ANIMAL STUDIES: Potassium bromide, phenobarbital, or a combination of both is commonly used in the treatment of canine epilepsy. Several cases of clinical pancreatitis have been reported in dogs after treatment with potassium bromide. In a retrospective study, at least 10% of dogs receiving potassium bromide/phenobarbital combination therapy, compared with 0.3% of dogs receiving phenobarbital monotherapy, had probable pancreatitis. Pancreatitis may be a more frequent and more serious adverse effect of potassium bromide/phenobarbital combination therapy than has been reported previously. Bromide toxicosis was diagnosed in an 8-year-old Labrador Retriever that had been treated for epilepsy with potassium bromide, at a dosage of 29 mg/kg of body weight/d. Clinical signs included hind limb weakness, ataxia, and disorientation. Renal insufficiency, diagnosed by determination of endogenous creatinine clearance, was believed to be responsible for the development of bromide toxicosis in this dog. Two cases of panniculitis associated with administration of potassium bromide in dogs are reported. Both dogs were treated with potassium bromide for idiopathic epilepsy for over 1 year. Dose increases in both cases were associated with panniculitis, characterized by painful subcutaneous nodules in a generalized distribution over the trunk. Nodule eruption waxed and waned in one dog and was persistent in the other. In both cases, panniculitis was accompanied by lethargy and pyrexia. ECOTOXICITY STUDIES: The effects of potassium bromide on the aquatic organisms were far smaller than those of potassium bromate and sodium bromate.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
副作用
神经毒素 - 其他中枢神经系统神经毒素
Neurotoxin - Other CNS neurotoxin
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
Bromide treatment was successful in controlling seizures in an 11-year-old Dachshund with epilepsy and presumptive phenobarbital-associated hepatopathy. Because bromide does not induce liver enzyme activity and does not seem to be hepatotoxic, it can be used to control seizures in dogs with concurrent epilepsy and hepatic disease. In this dog, institution of a special calculolytic diet with high chloride content was associated with a decrease in serum bromide concentrations and the recurrence of seizures. High chloride intake increases the elimination of bromide in dogs, leading to higher dosage requirements for bromide in dogs fed high-chloride diets.
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
OBJECTIVE: Several methods have been described to measure adherence to prescribed drug therapy. However, most of these have been shown to be inaccurate. Bromide is an anion that is readily absorbed in the gut and has an elimination half-life of about 12 days. In the present study, we investigated the pharmacokinetic properties of bromide with the objective to use it as a measure of drug adherence. METHODS: Three groups of each 8 healthy volunteers took 15, 24 or 30 mg potassium bromide, respectively, daily for 20 weeks. Serum concentrations of bromide were measured every two weeks. RESULTS: There was a linear relationship between the daily dosage taken and the mean increase of bromide concentration. In every group considerable inter-individual variability was seen. Correction for body weight resulted in an improved correlation between daily bromide dose and increase in concentration (r=0.78, p<0.01). CONCLUSIONS: Unfortunately, the inter-individual variability in clearance of bromide was considerable. This limits the use of bromide to primarily measuring adherence in individual patients during long term follow-up. Bromide appears to be a potentially useful marker to be added to drugs for assessment of individual adherence to long term drug therapy. This needs to be investigated in various patients, particularly for patients with relatively asymptomatic diseases (e.g. hypertension).
OBJECTIVE: To determine the pharmacokinetics of potassium bromide (KBr) in horses after single and multiple oral doses. ANIMALS: Twelve adult Standardbred and Thoroughbred mares. PROCEDURE: Horses were randomly assigned to two treatment groups. Group 1 horses were given a single oral dose of 120 mg/kg potassium bromide. Part 2 of the study evaluated a loading dose of 120 mg/kg KBr daily by stomach tube for 5 days, followed by 40 mg/kg daily in feed for 7 days. Serum concentrations of KBr were measured to construct concentration versus time curves and to calculate pharmacokinetic parameters. Treated horses were monitored twice daily by clinical examination. Serum concentrations of sodium, potassium and chloride ions and partial pressures of venous blood gases were determined. RESULTS: Maximum mean serum concentration following a single dose of KBr (120 mg/kg) was 423 +/- 22 ug/mL and the mean elimination half-life was 75 +/- 14 hr. Repeated administration of a loading dose of KBr (120 mg/kg once daily for 5 day) gave a maximum serum concentration 1639 +/- 156 ug/mL. The administration of lower, maintenance doses (40 mg/kg once daily) was associated with decreased serum bromide concentrations, which plateaued at approximately 1000 ug/mL. Administration of KBr was associated with significant but transient changes in serum potassium and sodium concentrations, and possible changes in base excess and plasma bicarbonate concentrations. High serum concentrations of bromide were associated with an apparent increase in serum chloride concentrations, when measured on an ion specific electrode. CONCLUSIONS: and clinical relevance Loading doses of 120 mg/kg daily over 5 days and maintenance doses of approximately 90 mg/kg of KBr administered once daily resulted in serum bromide concentrations consistent with therapeutic efficacy for the management of seizures in other species. The clinical efficacy of this agent as an anticonvulsant medication and/or calmative in horses warrants further investigation.
OBJECTIVE: To determine the pharmacokinetics of bromide in sheep after single intravenous (IV) and oral (PO) doses. PROCEDURE: Sixteen Merino sheep were randomly assigned to two treatment groups and given 120 mg/kg bromide, as sodium bromide IV or potassium bromide PO. Serum bromide concentrations were determined by colorimetric spectrophotometry. RESULTS: After IV administration the maximum concentration (Cmax) was 822.11 +/- 93.61 mg/L, volume of distribution (Vd ) was 0.286 +/- 0.031 L/kg and the clearance (Cl) was 0.836 +/- 0.255 mL/hr/kg. After PO administration the Cmax was 453.86 +/- 43.37 mg/L and the time of maximum concentration (Tmax ) was 108 +/- 125 hr. The terminal half-life of bromide after IV and PO administration was 387.93 +/- 115.35 hr and 346.72 +/- 94.05 hr, respectively. The oral bioavailability (F) of bromide was 92%. No adverse reactions were noted in either treatment group during this study. The concentration versus time profiles exhibited secondary peaks, suggestive of gastrointestinal cyclic redistribution of the drug. CONCLUSIONS AND CLINICAL RELEVANCE: When administered PO, bromide in sheep has a long half-life of approximately 14 days, with good bioavailability. Potassium bromide is a readily available, affordable salt with a long history of medical use as an anxiolytic, sedative and antiseizure therapy in other species. There are a number of husbandry activities and flock level neurological conditions, including perennial ryegrass toxicosis, in which bromide may have therapeutic or prophylactic application.
The pharmacokinetics of a multidose regimen of potassium bromide (KBr) administration in normal dogs was examined. KBr was administered at 30 mg/kg p.o. q 12 hr for a period of 115 days. Serum, urine, and cerebrospinal fluid (CSF) bromide (BR) concentrations were measured at the onset of dosing, during the accumulation phase, at steady-state, and after a subsequent dose adjustment. Median elimination half-life and steady-state serum concentration were 15.2 days and 245 mg/dL, respectively. Apparent total body clearance was 16.4 mL/day/kg and volume of distribution was 0.40 L/kg. The CSF:serum BR ratio at steady-state was 0.77. Dogs showed no neurologic deficits during maintenance dosing but significant latency shifts in waves I and V of the brainstem auditory evoked response were evident. Following a subsequent dose adjustment, serum BR concentrations of approximately 400 mg/dL were associated with caudal paresis in two dogs. Estimated half-life during the accumulation phase was shorter than elimination half-lives reported in other studies and was likely related to dietary chloride content. The range of steady-state concentrations achieved suggests individual differences in clearance and bioavailability between dogs. The described protocol reliably produced serum BR concentrations that are required by many epileptic patients for satisfactory seizure control.
1.周国泰,化学危险品安全技术全书,化学工业出版社,1997 2.国家环保局有毒化学品管理办公室、北京化工研究院合编,化学品毒性法规环境数据手册,中国环境科学出版社.1992 3.Canadian Centre for Occupational Health and Safety,CHEMINFO Database.1998 4.Canadian Centre for Occupational Health and Safety, RTECS Database, 1989
NOVEL PROCESS TO PREPARE PIOGLITAZONE VIA SEVERAL NOVEL INTERMEDIATES
申请人:Pandey Bipin
公开号:US20140088127A1
公开(公告)日:2014-03-27
A novel process for preparing thiazolidinediones, preferably Pioglitazone, as described. Also described are novel intermediates involved in its synthesis and process for their preparation and use in medicine.
PROCESSES AND INTERMEDIATES FOR MAKING A JAK INHIBITOR
申请人:Incyte Corporation
公开号:US20150183805A1
公开(公告)日:2015-07-02
This invention relates to processes and intermediates for making 1-1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, useful in the treatment of diseases related to the activity of Janus kinases (JAK) including inflammatory disorders, autoimmune disorders, cancer, and other diseases.
This invention provides a library of biphenyl derivatives of formula I:
1
wherein R
1
, R
2
, R
3
, R
4
, R
5
, R
6
, R
7
, W, a, b and c are as defined in the specification, or a salt or stereoisomer thereof. The library is useful for identifying compounds having both &bgr;
2
adrenergic receptor agonist and muscarinic receptor antagonist activity.
Accordingly, this invention also provides methods of evaluating or screening a library of biphenyl derivatives to identifying compounds having such bifunctional activity.