Absorption, Distribution and Excretion
Following inhalation, salbutamol acts topically on bronchial smooth muscle and the drug is initially undetectable in the blood. After 2 to 3 hours low concentrations are seen, due presumably to the portion of the dose which is swallowed and absorbed in the gut. In particular, the systemic levels of salbutamol are low after inhalation of recommended doses. A trial conducted in 12 healthy male and female subjects using a higher dose (1,080 mcg of albuterol base) showed that mean peak plasma concentrations of approximately 3 ng/mL occurred after dosing when salbutamol was delivered using propellant HFA-134a. The mean time to peak concentrations (Tmax) was delayed after administration of VENTOLIN (salbutamol) HFA (Tmax = 0.42 hours) as compared with CFC-propelled salbutamol inhaler (Tmax = 0.17 hours).
After oral administration, 58-78% of the dose is excreted in the urine in 24 hours, approximately 60% as metabolites. A small fraction is excreted in the feces.
The volume of distribution recorded for intravenously administered salbutamol has been recorded as 156 +/- 38 L.
The renal clearance of salbutamol has been documented as 272 +/- 38 ml/min after oral administration and 291 +/- 70 ml/min after intravenous administration. Furthermore, the renal clearance of the predominant sulfate conjugate metabolite was recorded as 98.5 +/- 23.5 ml/min following oral administration.
Elimination: Renal, 69 to 90% (60% as the metabolite). Fecal, 4%.
Extended-release tablets: Availability is approximately 80% of that for tablets after a single dose, regardless of whether or not taken with food, but is 100% of that for immediate-release tablets at steady-state. Food decreases the rate of absorption without affecting bioavailability.
Rapidly and well absorbed following oral administration.
Time to peak concentration: Syrup: within 2 hours. Tablets: 2 to 3 hours.
It is not known whether albuterol is distributed into human breast milk

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Metabolism / Metabolites
Salbutamol is not metabolized in the lung but is converted in the liver to the 4'-o-sulphate (salbutamol 4'-O-sulfate) ester, which has negligible pharmacologic activity. It may also be metabolized by oxidative deamination and/or conjugation with glucuronide. Salbutamol is ultimately excreted in the urine as free drug and as the metabolite.
Metabolized through sulfate conjugation to its inactive 4'-O-sulfate ester by phenol sulphotransferase (PST). The (R)-enantiomer of albuterol is preferentially metabolized (ten fold) by PST compared to the (S)-enantiomer of albuterol.
Hydrolyzed by esterases in tissue and blood to the active compound colterol. The drug is also conjugatively metabolized to salbutamol 4'-O-sulfate.
Route of Elimination: Approximately 72% of the inhaled dose is excreted in the urine within 24 hours, 28% as unchanged drug and 44% as metabolite.
Half Life: 1.6 hours

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Biological Half-Life
The elimination half-life of inhaled or oral salbutamol has been recorded as being between 2.7 and 5 hours while the apparent terminal plasma half-life of albuterol has been documented as being approximately 4.6 hours.
Elimination: 3.8 to 6 hours.

Toxicity Summary
Salbutamol is a beta(2)-adrenergic agonist and thus it stimulates beta(2)-adrenergic receptors. Binding of albuterol to beta(2)-receptors in the lungs results in relaxation of bronchial smooth muscles. It is believed that salbutamol increases cAMP production by activating adenylate cyclase, and the actions of salbutamol are mediated by cAMP. Increased intracellular cyclic AMP increases the activity of cAMP-dependent protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular calcium concentrations. A lowered intracellular calcium concentration leads to a smooth muscle relaxation and bronchodilation. In addition to bronchodilation, salbutamol inhibits the release of bronchoconstricting agents from mast cells, inhibits microvascular leakage, and enhances mucociliary clearance.

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Toxicity Data
LD₅₀=1100 mg/kg (orally in mice)

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Interactions
Following single-dose IV or oral administration of albuterol to healthy individuals who had received digoxin for 10 days, a 16-22% decrease in serum digoxin concentration was observed.
Epinephrin, other orally inhaled sympathomimetic amines: May increase sympathomimetic effects and risk of toxicity. Avoid use together /with albuterol/.
MAO inhibitors, tricyclic antidepressants: Serious cardiovascular effects and risk of toxicity. Avoid use together /with albuterol/.
Propanolol, other beta blockers: May antagonize effects of albuterol. Use together cautiously.

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Non-Human Toxicity Values
LD50 Mouse oral > 2 g/kg

Clin Sci (Lond).1986 Feb;70(2):159-65.

Therapeutic Uses
Bronchodilator; tocolytic
Albuterol .... /is/ indicated for the symptomatic treatment of bronchial asthma and for treatment of reversible bronchospasm that may occur in association with bronchitis, pulmonary emphysema, and other obstructive airway diseases. /Included in US product labeling/
Albuterol is indicated a a temporary treatment option for hyperkalemia in acute situations in pediatric patients. /NOT included in US product labeling/
/ExpTher/ Orally inhaled albuterol has been used investigationally to prevent or alleviate episodes of muscle paralysis in the treatment of some patients with hyperkalemic familial periodic paralysis.

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Drug Warnings
Tremor appears to be the most frequent reported adverse effect of albuterol, occurring in up to 20% of patients in clinical trials with various dosage forms of the drug. Other frequently reported adverse effects of albuterol include nervousness, nausea, tachycardia, palpitations, chest pain and dizziness. ...
Albuterol also has been reported to cause maternal and fetal tachycardia and hyperglycemia (especially in patients with diabetes), as well as maternal hypotension, acute congestive heart failure, pulmonary edema, and death.
Albuterol may delay preterm labor. Caution is recommended with use for bronchospasm in pregnant patients because of possible interference with uterine contractility.
Pregnancy risk category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./
For more Drug Warnings (Complete) data for ALBUTEROL (22 total), please visit the HSDB record page.

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Pharmacodynamics
Salbutamol (INN) or albuterol (USAN), a moderately selective beta(2)-receptor agonist similar in structure to terbutaline, is widely used as a bronchodilator to manage asthma and other chronic obstructive airway diseases. The R-isomer, levalbuterol, is responsible for bronchodilation while the S-isomer increases bronchial reactivity. The R-enantiomer is available and sold in its pure form as levalbuterol and subsequently may produce fewer side-effects with only the R-enantiomer present - although this has not been formally demonstrated. After oral and parenteral administration, stimulation of the beta receptors in the body, both beta-1 and beta-2, occurs because (a) beta-2 selectivity is not absolute, and (b) higher concentrations of salbutamol occur in the regions of these receptors with these modes of administration. This results in the beta-1 effect of cardiac stimulation, though not so much as with isoprenaline, and beta-2 effects of peripheral vasodilatation and hypotension, skeletal muscle tremor, and uterine muscle relaxation. Metabolic effects such as hyperinsulinemia and hyperglycemia also may occur, although it is not known whether these effects are mediated by beta-1 or beta-2 receptors. The serum potassium levels have a tendency to fall.

C13H21NO3

239.31

239.152

18559-94-9

Salbutamol hemisulfate;51022-70-9;Salbutamol-d3;1219798-60-3;Salbutamol-d9;1173021-73-2;Salbutamol-d9 acetate;1781417-68-2

2083

White to off-white solid powder

1.2±0.1 g/cm3

433.5±40.0 °C at 760 mmHg

157-158ºC

159.5±17.9 °C

0.0±1.1 mmHg at 25°C

1.566

0.01

4

4

5

17

227

0

NDAUXUAQIAJITI-UHFFFAOYSA-N

NDAUXUAQIAJITI-UHFFFAOYSA-N

4-[2-(tert-butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol

Salbutamol Albuterol Proventil Sultanol Aerolin Albuterol Sulfate Proventil Salbutamol Sultanol Ventolin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~417.87 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (10.45 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (10.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)