Fluticasone Propionate

Fluticasone propionate is a steroid medication. When inhaled it is used for the long-term management of asthma and COPD. In the nose, it is used for hay fever and nasal polyps. It can also be used for mouth ulcers. It works by decreasing inflammation.

Fluticasone propionate was patented in 1980 and approved for medical use in 1990. It is available as a generic medication. In 2020, fluticasone was the 23rd most commonly prescribed medication in the United States, with more than 24 million prescriptions.

Structure:

Physicochemical Data:

IUPAC Name     S-(fluoromethyl)-6α,9-difluoro-11β, 17-dihydroxy-16α-methyl-3-oxoandrosta-1, 4-diene-17β-carbothioate, 17-propanoate
CAS Number80474-14-2
Molecular Formula
C25H31F3O5S
Molecular Mass500.57 g·mol−1
Melting Point272-273°C (decomp)
Density 

Pharmacokinetic Data:

AbsorptionIntranasal bioavailability of fluticasone propionate is <2% and oral bioavailability is <1%. Intranasal exposure results in the majority of the dose being swallowed. Topical absorption of fluticasone propionate is very low but can change depending on several factors including integrity of the skin and the presence of inflammation or disease. A study of 24 healthy Caucasian males showed an inhaled bioavailability of 9.0%.
Volume of DistributionThe volume of distribution of intravenous fluticasone propionate is 4.2L/kg. A study of 24 healthy Caucasian males showed a volume of distribution at a steady state of 577L following intravenous administration.
Protein BindingFluticasone propionate is 99% protein-bound in serum. Topical fluticasone propionate is only 91% protein-bound in serum, however.
MetabolismFluticasone propionate is cleared from hepatic metabolism by cytochrome P450 3A4. Fluticasone propionate is hydrolyzed at the FIVE-S-fluoromethyl carbothioate group, forming an inactive metabolite.
Route of EliminationFluticasone propionate is mainly eliminated in the feces with <5% eliminated in the urine.
Half-life7.8 hours for intravenous fluticasone propionate. A study of 24 healthy Caucasian males shows a half-life of 14.0 hours following intravenous administration and 10.8 hours following inhalation.
Clearance1093mL/min for fluticasone propionate. A study of 24 healthy Caucasian males showed a clearance of 63.9L/h following intravenous administration.
ToxicityFluticasone propionate’s use in specific populations has not been well studied. Fluticasone propionate is not carcinogenic, mutagenic, or clastogenic, nor did it affect fertility in animal studies. Subcutaneous fluticasone propionate has been shown to produce teratogenic effects in rats though oral administration does not. Generally, there are no reported adverse effects with fluticasone in pregnancy. Fluticasone propionate in human milk may cause growth suppression, effects on endogenous corticosteroid production, or other effects. Pediatric patients treated with fluticasone propionate ointment experienced adrenal suppression. Geriatric patients treated with fluticasone propionate did not show any difference in safety or efficacy compared to other patient groups, though older patients may be more sensitive to adverse effects. There is no difference in the clearance of fluticasone propionate across genders or race. Patients with hepatic impairment should be closely monitored due to the elimination mechanism.

References:

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