Chemical Properties
White Solid
Originator
Budecort,AstraZeneca
Uses
A non-halogenated glucocorticoid related to triamcinolone hexacetonide. Used as an antiinflammatory agent
Uses
Budesonide is a glucocorticoid steroid that activates the glucorcorticoid receptor with an EC50 value of 12.4 nM. Like other glucocorticoids, budesonide reduces inflammation and has utility in inflammatory diseases, like asthma and inflammatory bowel disease. Also like other glucocorticoids, budesonide may be abused by athletes.[Cayman Chemical]
Uses
laxative, antineoplastic
Uses
The oral capsule is used for the treatment of mild to moderate active Crohn's disease. The oral tablet is used for induction of remission in patients with active, mild to moderate ulcerative colitis. The oral inhalation formulation is used for the treatme
Definition
ChEBI: A glucocorticoid steroid having a highly oxygenated pregna-1,4-diene structure. It is used mainly in the treatment of asthma and non-infectious rhinitis and for treatment and prevention of nasal polyposis.
Manufacturing Process
50 grams of desonide (16α-hydroxyprednisolone-16,17-acetonide) and
immediately thereafter 12.5 ml of butyraldehyde were added to 500 ml of
70% hydrofluoric acid solution at -5°C, and the mixture was stirred at 0°C
one hour and then poured into 5 liters of demineralized water at 0°C. The
precipitate was filtered, washed to neutrality with water and dried under
vacuum to give 51 g of pure budesonide with an A/B epimer ratio of 9/91.
Brand name
Entocort (AstraZeneca);
Pulmicort (AstraZeneca); Rhinocort (AstraZeneca).
Therapeutic Function
Corticosteroid
General Description
Budesonide (Pulmicort Turbohaler,Rhinocort) is extensively metabolized in the liver, with 85%to 95% of the orally absorbed drug metabolized by the firstpasseffect. The major metabolites are 6β-hydroxybudesonideand 16α-hydroxyprednisolone, both with less than1% of the activity of the parent compound. Metabolism involvesthe CYP3A4 enzyme, so coadministration of budesonidewith a known CYP3A4 inhibitor should be monitoredcarefully.
General Description
Budesonide, 16α,17-[butylidenebis-(oxy)]-11β,21-dihydroxypregna-1,4-diene-3, 20-dione (Entocort), in oral capsules is used to treat Crohn disease. Theaffinity for the GC is approximately 200-fold greater than thatof hydrocortisone and 15-fold greater than that of prednisolone.Budesonide is a mixture of epimers, with the 22Rform having twice the affinity for the GR of the S epimer.This GC is metabolized by CYP3A4, and its levels can be increasedin the presence of potent CYP3A4 inhibitors.Budesonide is also used in an inhaled formulation for thetreatment of asthma.
Biological Activity
Synthetic anti-inflammatory glucocorticoid that displays chemopreventive activity. Prevents formation of lung adenomas and adenocarcinomas in mice following inhalation or oral administration. Reverses DNA hypomethylation and modulates expression of cancer related genes.
Biochem/physiol Actions
Budesonide is a second generation glucocorticoid with low systemic absorption. It is used as an anti-inflammatory agent in the treatment of asthma, rhinitis, and inflammatory bowel disease. It inhibits the expression of chemokine mRNA and production of eotaxin and RANTES protein in primary human bronchial epithelial cells. Budesonide is currently in clinical trials for the prevention of lung cancer. It shows inhibitory effects on benzo[a]pyrene-induced carcinogenesis of the lung in mice.
Mechanism of action
Budesonide is an acetal formed between the 16α,17α-dihydroxyl groups and butanal. It is a nonhalogenated glucocorticoid with a 16,17-acetal that decreases the mineralocorticoid activity. In receptor affinity studies, the R-epimer was twofold more active than the S-epimer. Because the C-21 hydroxy is free, budesonide is not a prodrug and is active as administered. Only 34% of the metered dose of inhaled budesonide reaches the lung.
Pharmacology
While budesonide is well absorbed from the GI tract, its oral
bioavailability is low (about 10%), primarily because
of extensive first-pass metabolism in the liver. Two major
metabolites (16α-hydroxyprednisolone and 6β-
hydroxybudesonide) are formed via the cytochrome
P450 3A enzyme. In vitro studies on the binding of the
two primary metabolites to the corticosteroid receptor
indicate that their affinity for the receptor is less than
1% of that of the parent compound. It is hoped that use
of this drug will avoid the long-term adverse reactions
seen with systemically active corticosteroids.
Clinical Use
Recently, budesonide (Entecort EC) has been approved
for the treatment of mildly to moderately active
Crohn’s disease involving the ileum and/or ascending
colon.
Synthesis
Budesonide is prepared by reacting 16α-hydroxyprednisolone with n-butyraldehyde in 1,4-dioxane using perchloric acid as a catalyst, and the resulting crude product is purified via hot slurry in ethyl acetate to yield pure budesonide[2].
Veterinary Drugs and Treatments
While there are inhalational forms of the medication for treating
asthma or allergic rhinitis, most veterinary interest involves its potential
oral use to treat inflammatory intestinal diseases in small animals
that are either refractory to, or intolerant of, systemic steroids.
In humans, oral budesonide is indicated for Crohn’s disease.
Drug interactions
Potentially hazardous interactions with other drugs
Aldesleukin: avoid concomitant use.
Antibacterials: metabolism accelerated by rifamycins.
Anticoagulants: efficacy of coumarins and
phenindione may be altered.
Antiepileptics: metabolism accelerated by
carbamazepine, fosphenytoin, phenobarbital,
phenytoin and primidone.
Antifungals: concentration of inhaled and oral
budesonide increased by itraconazole and ketoconazole.
Antivirals: concentration of inhaled, intranasal and
rectal budesonide increased by ritonavir.
Cobicistat: concentration possibly increased by
cobicistat - increased risk of adrenal suppression.
Grapefruit juice: concentration of oral budesonide
increased - avoid.
Vaccines: high dose corticosteroids can impair
immune response to vaccines - avoid with live
vaccines.
Metabolism
Budesonide was metabolized three- to sixfold more rapidly than triamcinolone acetonide.
The pharmacokinetics of budesonide after inhalation, oral, and IV administration displayed a mean plasma
half-life of 2.8 hours and a systemic bioavailability of approximately 10% after oral administration (Table 33.5)
(101). Pulmonary bioavailability is less than 40% after inhalation (70–75% after correction for the amounts of
budesonide deposited in the inhalation device and oral cavity). No oxidative metabolism was observed in the
lung. When given by inhalation, 32% of the dose is excreted in the urine as metabolites, 15% in the feces, and
41% of the dose remained in the mouthpiece of the inhaler. Following intranasal administration, very little of
intranasal budesonide is absorbed from the nasal mucosa. Much of the intranasal dose (~60%) was swallowed,
however, and remained in the GI tract to be excreted unchanged in the feces, whereas that fraction of the
intranasal dose that was absorbed was extensively metabolized.
