PHARMACODYNAMICS Systemically, in vitro experiments show [DB08906] activates glucocorticoid receptors, inhibits nuclear factor kappa b, and inhibits lung eosinophilia in rats[F4361,F4364,A177130]. [DB00588] performs similar activity but is not stated to affect nuclear factor kappa b[F4358][FDA Label]. [DB00588] as a topical formulation is also associated with vasoconstriction in the skin[F4355,A177118].

MOA [DB08906] and [DB00588] work through an unknown mechanism to affect the action of various cell types and mediators of inflammation[F4361,F4364,F4358]. In vitro experiments show [DB08906] activating glucocorticoid receptors, inhibiting nuclear factor kappa b, and inhibiting lung eosinophilia in rats[F4361,F4364,A177130]. [DB00588] performs similar activity but is not stated to affect nuclear factor kappa b[F4358,F4355].

INDICATION Fluticasone's 2 esters are indicated as inhalers for the treatment and management of asthma by prophylaxis[FDA Label][F4364]as well as inflammatory and pruritic dermatoses[F4355]. A [DB00588] nasal spray is indicated for managing nonallergic rhinitis[F4358] while the [DB08906] nasal spray is indicated for treating season and perennial allergic rhinitis[F4361,A177130].

ROE [DB08906] is eliminated ≥90% in the feces and 1-2% in the urine[F4361,F4364].; ; [DB00588] is mainly eliminated in the feces with <5% eliminated in the urine[F4358,A176918][FDA Label].

METABOLISM [DB08906] and [DB00588] are cleared from hepatic metabolism by cytochrome P450 3A4[F4361,F4364,F4358,A177121][FDA Label]. Both are hydrolysed at the FIVE-S-fluoromethyl carbothioate group, forming an inactive metabolite[F4361,F4355,A177118][FDA Label].

ABSORPTION Intranasal exposure of [DB08906] results in patients swallowing a larger portion of the dose[F4361,A177118]. However, absorption is poor and metabolism is high, therefore there is negligible systemic exposure with a nasal bioavailability of 0.50% and oral bioavialability of 1.26%[F4361,A7490]. Inhaled bioavailability is 13.9%[F4364]. A study of 24 healthy Caucasian males showed an inhaled bioavailability of 6.3-18.4%[A7490].; ; Intranasal bioavailability of [DB00588] is <2%, and oral bioavailability is <1%[F4358][FDA Label]. Intranasal exposure results in the majority of the dose being swallowed[A177118]. Topical absorption of [DB00588] is very low but can change depending on a number of factors including integrity of the skin and the presence of inflammation or disease[F4355]. A study of 24 healthy Caucasian males showed an inhaled bioavailability of 9.0%[A7490].

HALF-LIFE 15.1 hours for intranasal [DB08906][F4361] and 24 hours for the inhaled formulation[F4364]. A study of 24 healthy Caucasian males showed a half life of 13.6 hours following intravenous administration and 17.3-23.9 hours followed inhalation[A7490].; ; 7.8 hours for intravenous [DB00588][F4358][FDA Label]. A study of 24 healthy Caucasian males shows a half life of 14.0 hours following intravenous administration and 10.8 hours following inhalation[A7490].

TOXICITY [DB08906] administered nasally may be associated with adrenal suppression or an increase in QTc interval though the association has not been well demonstrated in studies[F4361,A7488]. [DB08906] requires no dosage adjustment in renal impairment but must be used in caution in hepatic impairment due to the elimination mechanisms[F4361,F4364]. [DB08906] is not associated with carcinogenicity, mutagenicity, or impairment of fertility[F4361]. There are no well controlled studies in pregnancy or lactation though animal studies have shown teratogenicity and hypoadrenalism in the offspring of treated mothers and other corticosteroids are known to be excreted in breast milk[F4361]. Generally, there are no reported adverse effects with fluticasone in pregnancy[A177127]. Pediatric patients should be given the lowest possible dose and monitored for reduction in growth velocity[F4361,A7488]. There is insufficient evidence to determine whether geriatric patients respond differently to other patients[F4361]. Systemic exposure may be 27-49% higher in Japanese, Korean, and Chinese patients compared to Caucasian patients[F4364]. Caution should be exercised in these patients and the benefit and risk should be assessed before deciding on a treatment[F4361].; ; [DB00588]'s use in specific populations has not been well studied[F4358]. [DB00588] is not carcinogenic, mutagenic, or clastogenic, nor did it affect fertility in animal studies[F4358][FDA Label]. Subcutaneous [DB00588] has been shown to produce teratogenic effects in rats though oral administration does not[F4355][FDA Label]. Generally, there are no reported adverse effects with fluticasone in pregnancy[A177127]. [DB00588] in human milk may cause growth suppression, effects on endogenous corticosteroid production, or other effects[F4355,A7488]. Pediatric patients treated with [DB00588] ointment experienced adrenal suppression[F4355]. Geriatric patients treated with [DB00588] did not show any difference in safety or efficacy compared to other patient groups, though older patients may be more sensitive to adverse effects[F4355]. There is no difference in the clearance of [DB00588] across genders or race[FDA Label]. Patients with hepatic impairment should be closely monitored due to the elimination mechanism[FDA Label][A176918].

DESCRIPTION Fluticasone is an inhaled corticosteroid used for respiratory research. Fluticasone is a Smo agonist with an IC50 value of 99 nM. Fluticasone activates Hedgehog signaling and promotes the proliferation of primary neuronal stem or precursor cells[1][2].

DESCRIPTION The DrugBank entry listed here refers to fluticasone propionate with CAS registry number 80474-14-2. ChEMBL lists fluticasone propionate as a glucocorticoid receptor agonist, but not the fluticasone parent molecule.

Breo Ellipta®, approved by the FDA in 2013, is a fixed-dose formulation containing fluticasone furoate and . (GtoPdb)