Budesonide is metabolized in the liver by the cytochrome P-450 (CYP) isoenzyme 3A4; the 2 main metabolites have less than 1% of affinity for glucocorticoid receptors than the parent compound. Budesonide is excreted in urine and feces as metabolites.
Asthma is one of the most prevalent diseases in the world, for which the mainstay treatment has been inhaled glucocorticoids (GCs). Despite the widespread use of these drugs, approximately 30% of asthma sufferers exhibit some degree of steroid insensitivity or are refractory to inhaled GCs. One hypothesis to explain this phenomenon is interpatient variability in the clearance of these compounds. The objective of this research is to determine how metabolism of GCs by the CYP3A family of enzymes could affect their effectiveness in asthmatic patients. In this work, the metabolism of four frequently prescribed inhaled GCs, triamcinolone acetonide, flunisolide, budesonide, and fluticasone propionate, by the CYP3A family of enzymes was studied to identify differences in their rates of clearance and to identify their metabolites. Both interenzyme and interdrug variability in rates of metabolism and metabolic fate were observed. CYP3A4 was the most efficient metabolic catalyst for all the compounds, and CYP3A7 had the slowest rates. CYP3A5, which is particularly relevant to GC metabolism in the lungs, was also shown to efficiently metabolize triamcinolone acetonide, budesonide, and fluticasone propionate. In contrast, flunisolide was only metabolized via CYP3A4, with no significant turnover by CYP3A5 or CYP3A7. Common metabolites included 6 Beta-hydroxylation and Delta (6)-dehydrogenation for triamcinolone acetonide, budesonide, and flunisolide. The structure of Delta (6)-flunisolide was unambiguously established by NMR analysis. Metabolism also occurred on the D-ring substituents, including the 21-carboxy metabolites for triamcinolone acetonide and flunisolide. The novel metabolite 21-nortriamcinolone acetonide was also identified by liquid chromatography-mass spectrometry and NMR analysis.
IDENTIFICATION AND USE: Budesonide (trade names: Rhinocort, MMX) is a prescription medication approved for the treatment of allergic rhinitis (Rhinocort nasal spray) and mild to moderate Crohn's disease (MMX, enteric coated capsules). HUMAN EXPOSURE AND TOXICITY: Patch tests have indicated that budesonide can produce delayed allergic reactions, and atopic dermatitis. In cases of inhalational exposure, periorificial dermatitis has been reported. In cases of oral administration, Candida albicans esophagitis, dysphagia, elevated blood pressure, lower extremity edema, and weight gain have been reported, although some of these adverse events may have been the result of a drug interaction with voriconazole. Epidemiological studies have found an increased risk of pneumonia, cardiac dysrhythmias, cataracts, and fractures associated with inhaled budesonide use. Additional epidemiological studies have found that budesonide inhalation during pregnancy may be a risk factor for offspring endocrine and metabolic disturbances. Low birth weight has also been reported. In children taking budesonide for persistent asthma, slower linear growth, slow weight gain, and slow skeletal maturation have also been observed. Localized Candidal infections of the nose and pharynx has been reported during intranasal budesonide therapy. Patients may be at an increased risk for certain infections, such as Varicella (chickenpox). In children and adolescents, administration of budesonide may cause growth suppression. It may also cause acute or delayed hypersensitivity reactions. Hypoadrenalism may occur in infants of mothers receiving corticosteroid therapy during pregnancy. ANIMAL STUDIES: In carcinogenicity studies, hepatocellular tumors and gliomas have been observed in rats that received oral budesonide. In female rats that received budesonide subcutaneously, a decrease in prenatal viability and viability of pups during pregnancy and lactation was observed. Pyloric hyalinization was detected in mice that received budesonide orally.
Long term therapy with budesonide has not been linked to elevations in serum enzyme levels, and in clinical trials rates of ALT elevations were similar with budesonide as with placebo treatment. In controlled trials, there were no reported cases of clinically apparent liver injury associated with its use. Unlike conventional systemically administered corticosteroids, budesonide has not been linked to episodes of reactivation of hepatitis B. Budesonide has been used in severe autoimmune liver diseases without evidence that it causes worsening of liver injury. Because it can improve serum aminotransferase elevations in patients with autoimmune hepatitis, its withdrawal may be followed by rebound elevations as also occurs with conventional corticosteroid therapy. In addition, there has been a single case report of acute serum aminotransferase elevations during budesonide therapy that resolved when the drug was stopped, but documentation was limited and the patient was on multiple other potentially hepatotoxic drugs.
◉ Summary of Use during Lactation:The amounts of inhaled budesonide excreted into breastmilk are minute and infant exposure is negligible. When taken by mouth, budesonide is only about 9% bioavailable; bioavailability in the infant is likely to be similarly low for any budesonide that enters the breastmilk. Expert opinion considers inhaled, nasal and oral corticosteroids acceptable to use during breastfeeding.
◉ Effects in Breastfed Infants:None reported with any corticosteroid.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
Steroid psychosis has been well described with oral glucocorticoids, however, our search of the literature did not identify an association between delirium and the combination of inhaled glucocorticoids and long-acting beta-agonists. We describe the occurrence of delirium with the combination of an inhaled glucocorticoid and bronchodilator. An elderly male described confusion and hallucinations within 1 week after initiation of budesonide/formoterol for chronic obstructive pulmonary disease. The combination inhaler was discontinued with resolution of symptoms. Several weeks later, the patient was hospitalized and restarted on the combination inhaler. The patient was alert and oriented on admission, however, confusion and hallucinations progressed throughout his hospital stay. The combination inhaler was discontinued and his confusion and hallucinations resolved by discharge. The temporal relationship of these events and a probable Naranjo association allows for reasonable assumption that the use of the budesonide/formoterol combination inhaler caused or contributed to the occurrences of delirium in this elderly patient. The onset of delirium was likely due to the systemic absorption of the glucocorticoid from lung deposition, complicated in an individual with several predisposing risk factors for delirium. Health care providers should be aware of this potential adverse drug reaction when prescribing inhaled medications to older patients at risk for delirium.
A 48-year-old woman with HIV infection developed Cushingoid features while she was taking ritonavir-boosted darunavir. Cushing's syndrome was confirmed due to the drug interaction between ritonavir and budesonide. Diagnosis of iatrogenic Cushing's syndrome in HIV-positive patients who are on ritonavir-boosted protease inhibitors (PIs) presents a clinical challenge due to similar clinical features of lipohypertrophy related to ritonavir-boosted PIs. Although this complication has been widely described with the use of inhaled fluticasone, the interaction with inhaled budesonide at therapeutic dose is not widely recognized.
When budesonide is administered intranasally, approximately 34% of a dose reaches systemic circulation. Mean peak plasma budesonide concentrations are achieved in about 0.7 hours.
Inhaled corticosteroids (ICS) are mainstay treatment of asthma and chronic obstructive pulmonary disease. However, highly lipophilic ICS accumulate in systemic tissues, which may lead to adverse systemic effects. The accumulation of a new, highly lipophilic ICS, ciclesonide and its active metabolite (des-CIC) has not yet been reported. Here, we have compared tissue accumulation of des-CIC and an ICS of a moderate lipophilicity, budesonide (BUD), after 14 days of once-daily treatment in mice. Single, three or 14 daily doses of [(3) H]-des-CIC or [(3) H]-BUD were administered subcutaneously to male CD1 albino mice, which were killed at 4 hrs, 24 hrs or 5 days after the last dose. Distribution of tissue concentration of radioactivity was studied by quantitative whole-body autoradiography. Pattern of radioactivity distribution across most tissues was similar for both corticosteroids after a single as well as after repeated dosing. However, tissue concentration of radioactivity differed between des-CIC and BUD. After a single dose, concentrations of radioactivity for both corticosteroids were low for most tissues but increased over 14 days of daily dosing. The tissue radioactivity of des-CIC at 24 hrs and 5 days after the 14th dose was 2-3 times higher than that of BUD in majority of tissues. Tissue accumulation, assessed as concentration of tissue radioactivity 5 days after the 14th versus 3rd dose, showed an average ratio of 5.2 for des-CIC and 2.7 for BUD (p < 0.0001). In conclusion, des-CIC accumulated significantly more than BUD. Systemic accumulation may lead to increased risk of adverse systemic side effects during long-term therapy.
Section 1. Chemical Product and Company Identification Budesonide Catalog YY448, YY1420, B1581, Common Name/ Number(s). Trade Name 51333-22-3 CAS# Manufacturer Commercial Name(s) Synonym Budesonide Section 4. First Aid Measures Check for and remove any contact lenses. In case of contact, immediately flush eyes with plenty of water for at least Eye Contact 15 minutes. Get medical attention. In case of contact, immediately flush skin with plenty of water. Cover the irritated skin with an emollient. Remove Skin Contact contaminated clothing and shoes. Wash clothing before reuse. Thoroughly clean shoes before reuse. Get medical attention. Serious Skin Contact Wash with a disinfectant soap and cover the contaminated skin with an anti-bacterial cream. Seek medical attention. Inhalation If inhaled, remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical attention. Serious Inhalation Not available. Do NOT induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an Ingestion unconscious person. Loosen tight clothing such as a collar, tie, belt or waistband. Get medical attention if symptoms appear. Serious Ingestion Not available. Section 5. Fire and Explosion Data Flammability of the Product May be combustible at high temperature. Auto-Ignition Temperature Not available. Not available. Flash Points Not available. Flammable Limits These products are carbon oxides (CO, CO2). Products of Combustion Fire Hazards in Presence of Slightly flammable to flammable in presence of heat. Various Substances Risks of explosion of the product in presence of mechanical impact: Not available. Explosion Hazards in Risks of explosion of the product in presence of static discharge: Not available. Presence of Various Substances SMALL FIRE: Use DRY chemical powder. Fire Fighting Media LARGE FIRE: Use water spray, fog or foam. Do not use water jet. and Instructions Not available. Special Remarks on Fire Hazards Not available. Special Remarks on Explosion Hazards Section 6. Accidental Release Measures Use appropriate tools to put the spilled solid in a convenient waste disposal container. Finish cleaning by spreading Small Spill water on the contaminated surface and dispose of according to local and regional authority requirements. Use a shovel to put the material into a convenient waste disposal container. Finish cleaning by spreading water on Large Spill the contaminated surface and allow to evacuate through the sanitary system. Budesonide Section 7. Handling and Storage Keep away from heat. Keep away from sources of ignition. Ground all equipment containing material. Do not Precautions ingest. Do not breathe dust. Wear suitable protective clothing. If ingested, seek medical advice immediately and show the container or the label. Avoid contact with skin and eyes. Keep container tightly closed. Keep container in a cool, well-ventilated area. Storage Section 8. Exposure Controls/Personal Protection Use process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below Engineering Controls recommended exposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to airborne contaminants below the exposure limit. Personal Protection Splash goggles. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent. Gloves. Personal Protection in Case Splash goggles. Full suit. Dust respirator. Boots. Gloves. A self contained breathing apparatus should be used to avoid inhalation of the product. Suggested protective clothing might not be sufficient; consult a specialist BEFORE of a Large Spill handling this product. Not available. Exposure Limits Section 9. Physical and Chemical Properties Solid. Odorless. Physical state and O dor appearance Not available. Taste 430.59 g/mole Molecular Weight White. Off-white. Color Not applicable. pH (1% soln/water) Not available. Boiling Point 226.5°C (439.7°F) Melting Point Not available. Critical Temperature Not available. Specific G
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