Lung bioavailability of hydrofluoroalkane fluticasone in young children when delivered by an antistatic chamber/mask

Khan, Yasmeen; Tang, Yufei; Hochhaus, Günther; Shuster, Jonathan J.; Spencer, Terry; Chesrown, Sarah E.; Hendeles, Leslie

doi:10.1016/j.jpeds.2006.08.022

Cited by 14 publications

(10 citation statements)

References 28 publications

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“…This is the first study to directly compare lung bioavailability of ICSs delivered by two different VHCs in a crossover design in children aged 1 to <4 yrs using a population pharmacokinetic approach. Our findings confirm the results of previous studies in young and older children in which differences in lung bioavailability, expressed as peak concentration, were observed when FP was delivered via different VHCs [7, 8]. …”

Section: Discussionsupporting

confidence: 91%

“…However, this method is suitable only for drugs that have negligible oral bioavailability to ensure that blood measurements reflect only drug that has been absorbed systemically from the lungs. Several published studies have documented differences in the delivery of inhaled corticosteroids (ICSs) to the lung with a metered-dose inhaler (MDI) attached to different VHCs by measuring blood levels [7, 8]. …”

mentioning

confidence: 99%

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Bioavailability of inhaled fluticasone propionateviachambers/masks in young children

Blake

Mehta

Spencer³

et al. 2011

Eur Respir J

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We determined lung bioavailability of a fluticasone propionate (FP) pressurised metred-dose inhaler (Flovent® HFA; GlaxoSmithKline, Research Triangle Park, NC, USA) administered via AeroChamber Plus® (Monaghan Medical, Plattsburgh, NY, USA) with Facemask and Babyhaler® (GlaxoSmithKline) valved holding chambers (VHCs) using a population pharmacokinetic approach. Children from 1 to <4 yrs of age with stable asthma but a clinical need for inhaled corticosteroid therapy were administered 88 µg FP hydrofluoroalkane (2 × 44 µg) twice daily delivered through the two devices in an open-label, randomised crossover manner for 8 days each. Patients were randomised to one of three sparse sampling schedules for blood collection throughout the 12-h dosing interval on the 8th day of each treatment for pharmacokinetic analysis. The area under the FP plasma concentration–time curve (AUC) was determined for each regimen. 17 children completed the study. The population mean AUC following FP with AeroChamber Plus® with Facemask was 97.45 pg·h·mL−1 (95% CI 85.49–113.32 pg·h·mL−1) and with Babyhaler® was 51.55 pg·h·mL−1 (95% CI 34.45–64.46 pg·h·mL−1). The relative bioavailability (Babyhaler®/AeroChamber Plus®) was 0.53 (95% CI 0.30–0.75). Clinically significant differences in lung bioavailability were observed between the devices. VHCs are not interchangeable, as differences in drug delivery to the lung may occur. A population pharmacokinetic approach can be used to determine lung bioavailability of FP.

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

Bioavailability of inhaled fluticasone propionateviachambers/masks in young children

Blake

Mehta

Spencer³

et al. 2011

Eur Respir J

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“…Available data in children indicate that the mean steady-state concentrations of FP in the systemic circulation range from 107 to 183 pg/mL, depending on the particular inhalation chamber used. 26 FP is a potent inactivator of CYP3A5, and to a lesser extent CYP3A4, such that drug which was not metabolized in the liver may inhibit its own metabolism. 12 Reduced enzyme activity by CYP3A4*22 has been associated with concentration-related toxicity by cyclosporine, including an increased risk of delayed graft function and decreased creatinine clearance in kidney transplant patients.…”

Section: Discussionmentioning

confidence: 99%

Fluticasone Propionate Pharmacogenetics: CYP3A4*22 Polymorphism and Pediatric Asthma Control

Stockmann

Fassl

Gaedigk

et al. 2013

The Journal of Pediatrics

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Objective To determine the relationship between allelic variations in genes involved in fluticasone propionate (FP) metabolism and asthma control among children with asthma managed with inhaled FP. Study design The relationship between variability in asthma control scores and genetic variation in drug metabolism was assessed by genotyping nine single nucleotide polymorphisms (SNPs) in CYP3A4, CYP3A5, and CYP3A7. Genotype information was compared with asthma control scores (0 = well-controlled to 15 = poorly-controlled), determined by using a questionnaire modified from the National Heart Lung and Blood Institute Expert Panel 3 guidelines. Results Our study cohort was comprised of 734 children with asthma (mean age 8.8 ± 4.3 years), who were predominantly male (61%) and non-Hispanic Whites (53%); 413 children (56%) were receiving inhaled glucocorticoids daily, of which FP was prescribed most frequently (65%). Among the children receiving daily FP, SNPs in the genes CYP3A5 and CYP3A7 were not associated with asthma control scores. In contrast, asthma control scores were significantly improved among 20 (7%) children with the CYP3A4*22 allele (median 3, range 0-6), as compared with the 201 patients without the CYP3A4*22 allele (median 4, range 0-15) (P=0.02). The presence of CYP3A4*22 was associated with improved asthma control scores by 2.1 points (95% CI: 0.5-3.8). Conclusions The presence of CYP3A4*22, which is associated with decreased hepatic CYP3A4 expression and activity, was accompanied by improved asthma control among FP treated children. Decreased CYP3A4 activity may improve asthma control with inhaled FP.

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“…27 On the other hand, antistatic chambers consistently deliver a higher amount of medication to the airways. 17,24,25,27,28 However, the clinical relevance of increased drug delivery has been minimally studied. One example of such a study examined the bronchodilator response during nocturnal bronchospasm in adults.…”

Section: Valved Holding Chamber Characteristicsmentioning

confidence: 99%

“…16 However, the type of VHC is important because the amount of drug delivered to the airways varies depending on the VHC used. 17,18 The FDA requires only in vitro studies of VHC for approval. Thus, these products are approved without a proof of safety, efficacy, or pulmonary deposition.…”

mentioning

confidence: 99%

Delivery of Medications by Metered Dose Inhaler Through a Chamber/Mask to Young Children with Asthma

ElMallah¹,

Hendeles²

2012

Pediatric Allergy, Immunology, and Pulmonology

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Delivery of inhaled medications to children with asthma by a small-volume nebulizer is an antiquated method. Delivery by metered dose inhaler through a valved holding chamber with mask is at least equally effective, but more convenient, safer, faster, and less expensive. In addition, antistatic chambers increase the amount of drug delivered to the airways. This is an advantage for albuterol, but could increase the risk of long-term systemic adverse effects of inhaled corticosteroids at higher doses. Comparison with Nebulizer DeliveryI n children under five years of age, inhaled medications are difficult to administer. The only two methods of medication delivery to this age group are the metered dose inhaler through a valved holding chamber with mask (MDI + VHC) and the small-volume nebulizer (SVN). Both can be used to administer a short-acting beta-agonist and an inhaled corticosteroid (ICS). However, the MDI + VHC method has several advantages over nebulizer delivery. [1][2][3][4][5] The MDI + VHC is more efficient, faster, more convenient, and less expensive than the SVN. 5,6 Furthermore, in the emergency department treatment of asthma in children 5-17 years, when albuterol was given by MDI + VHC with mouthpiece (6-10 puffs per dose repeated at 20-min intervals), there was less tachycardia than when given by nebulizer. 2 Finally, in children under five years of age with moderate-to-severe asthma exacerbations treated in the emergency department, albuterol given by MDI + VHC was more effective than by a nebulizer in decreasing hospitalization and improving clinical score. 1 However, prescribers and parents of young children often believe that a nebulizer is more effective than an MDI + VHC. On the contrary, it has been shown that 4-10 puffs of albuterol sulfate delivered by MDI + VHC per dose is as effective as 2.5 mg of albuterol delivered by SVN when both are administered at 15-30-min intervals to infants and preschool children. 4,5,7,8 The results of these studies apply to home treatment of exacerbations. However, another disadvantage of home nebulizer administration is that pathogenic organisms can be transmitted when nebulizers are not disinfected. 9 Budesonide inhalation suspension (Pulmicort Respules Ò and generics) is the only ICS available in the United States for nebulization. There are no studies comparing the delivery of budesonide by nebulizer to delivery by MDI + VHC in young children. However, a randomized, double-blind, placebo-controlled study has shown that fluticasone delivered through an MDI + VHC improves pulmonary function and controls symptoms in infants with recurrent wheeze. 10 Other studies have substantiated improved asthma control when an MDI + VHC was used to deliver fluticasone in children < 2 years as well as older preschool children. [11][12][13][14][15] Thus, the MDI + VHC is an efficient and effective way to deliver both albuterol and ICS to young children. However, as children get older, there is less rationale for using a VHC. For older children who can breath-hold, a dry powd...

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Lung bioavailability of hydrofluoroalkane fluticasone in young children when delivered by an antistatic chamber/mask

Cited by 14 publications

References 28 publications

Bioavailability of inhaled fluticasone propionateviachambers/masks in young children

Bioavailability of inhaled fluticasone propionateviachambers/masks in young children

Fluticasone Propionate Pharmacogenetics: CYP3A4*22 Polymorphism and Pediatric Asthma Control

Delivery of Medications by Metered Dose Inhaler Through a Chamber/Mask to Young Children with Asthma

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