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Lung Deposition (lung + deposition)
Selected AbstractsDosage regimens for inhaled therapy in children should be reconsideredJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 2 2002JH Wildhaber Abstract: In current asthma guidelines, dosage regimens for inhalation therapy in children are based on adult doses and are generally titrated per kilogram of bodyweight or per square metre of body surface area. However, these recommendations do not correspond well with current knowledge of aerosol therapy in childhood. Lung deposition of the aerosolised drug is the key determinant for clinical efficacy and for systemic side effects of inhalation therapy. Lung deposition increases with age, whereas lung deposition expressed as a percentage per kilogram bodyweight is age-independent. This finding is explained by the self-regulating effect of age-dependent airway anatomy on lung deposition. Therefore, it is more likely that adult doses translate into paediatric doses only by virtue of the differences in self-limiting pulmonary deposition when using the same absolute nominal doses of the medication. Adapting the adult dose to a paediatric dose calculated on body size might be unnecessary and could lead to insufficient pulmonary deposition of medication. These findings suggest that dosage regimens for inhalation therapy for children may have to be reconsidered, and should be determined from dose-ranging studies rather than calculated from adult doses based on body size. [source] The efficacy and safety of QVAR (hydrofluoroalkane-beclometasone diproprionate extrafine aerosol) in asthma (part 2): clinical experience in childrenINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2004C. P. Van Schayck Summary QVAR [hydrofluoroalkane-134a beclometasone dipropionate (BDP)] produces equivalent asthma control to chlorofluorocarbon-based BDP inhalers, at approximately half the daily dose in adults, a probable consequence of the increased lung deposition of QVAR that results from its greater fine particle fraction. Recent studies have relied on the clinical experience with QVAR in adults as a basis for investigations in childhood asthma. Design considerations, such as the use of the breath-actuated AutohalerÔ delivery device and measurement of direct health benefits, account for problems of variation in inspiratory flow, handling difficulties and low airways resistance that are associated with children. QVAR appears to be well tolerated in children with no clinically relevant adverse effects on adrenal function, bone metabolism or growth at recommended doses. [source] Dosage regimens for inhaled therapy in children should be reconsideredJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 2 2002JH Wildhaber Abstract: In current asthma guidelines, dosage regimens for inhalation therapy in children are based on adult doses and are generally titrated per kilogram of bodyweight or per square metre of body surface area. However, these recommendations do not correspond well with current knowledge of aerosol therapy in childhood. Lung deposition of the aerosolised drug is the key determinant for clinical efficacy and for systemic side effects of inhalation therapy. Lung deposition increases with age, whereas lung deposition expressed as a percentage per kilogram bodyweight is age-independent. This finding is explained by the self-regulating effect of age-dependent airway anatomy on lung deposition. Therefore, it is more likely that adult doses translate into paediatric doses only by virtue of the differences in self-limiting pulmonary deposition when using the same absolute nominal doses of the medication. Adapting the adult dose to a paediatric dose calculated on body size might be unnecessary and could lead to insufficient pulmonary deposition of medication. These findings suggest that dosage regimens for inhalation therapy for children may have to be reconsidered, and should be determined from dose-ranging studies rather than calculated from adult doses based on body size. [source] Relative lung and systemic bioavailability of sodium cromoglycate inhaled products using urinary drug excretion post inhalationBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2002Osama Aswania Abstract The relative lung and systemic bioavailability of sodium cromoglycate following inhalation by different methods have been determined using a urinary excretion pharmacokinetic method. On three separate randomised study days, 7 days apart, subjects inhaled (i) 4×5 mg from an Intal® metered dose inhaler (MDI), (ii) 4×5 mg from an MDI attached to a large volume spacer (MDI+SP) and (iii) 20 mg from an Intal Spinhaler® (DPI). Urine samples were provided at 0, 0.5, 1, 2, 5 and 24 h post dose. The mean (S.D.) amount of sodium cromoglycate excreted in the urine during the first 30 min post inhalation was 38.1 (27.5), 222.3 (120.3) and 133.1 (92.2) ,g following MDI, MDI+SP and DPI, respectively. The mean ratio (90% confidence interval) of these amounts excreted in the urine over the first 30 min for MDI+SP vs MDI, DPI vs MDI and MDI+SP vs DPI was 801.0 (358.0, 1244; p<0.002)%, 457.0 (244.0, 670.0; p<0.02)% and 262.4 (110.2, 414.5)%, respectively. Similarly for the 24 h cumulative amount of sodium cromoglycate excreted over the 24 h post inhalation the ratios were 375.4 (232.9, 517.9; p<0.005)%, 287.5 (183.4, 391.6; p<0.02)% and 211.4 (88.3, 334.5)%, respectively. The results highlight better lung deposition of sodium cromoglycate from a metered dose inhaler attached to a large volume spacer. Copyright © 2002 John Wiley & Sons, Ltd. [source] In vivo comparison of the relative systemic bioavailability of fluticasone propionate from three anti-static spacers and a metered dose inhalerBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2009Arun Nair WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Conventional spacers help overcome problems with co-ordination and may improve lung deposition and decrease oropharyngeal impaction. , Antistatic spacers eliminate electrostatic charge and may hence improve respirable dose delivery. , The systemic bioavailability of inhaled fluticasone propionate is primarily dependent on delivery by the pulmonary route and hence the performance of antistatic spacers can be evaluated using adrenal suppression as a sensitive surrogate for relative bioavailability to the lung after an inhalation. WHAT THIS STUDY ADDS , This study compares the relative bioavailability to the lung of inhaled fluticasone delivered via conventional pressurized metered dose inhalers (pMDI) and three antistatic spacers (plastic Zerostat-V, plastic Aerochamber Max, and metal Nebuchamber) in patients with asthma. , All three antistatic spacers when compared with pMDI significantly increased the relative bioavailability to the lungs of inhaled fluticasone in terms of relative adrenal suppression, and there were no significant differences between the plastic and metal antistatic spacers. AIMS The systemic bioavailability of inhaled fluticasone propionate (FP) depends primarily on lung absorption and can be quantified by measuring suppression of overnight and early morning urinary cortisol/creatinine (OUCC and EMUCC, respectively). The aim of the study was to determine the relative bioavailability of hydrofluoroalkane (HFA) FP to the lungs via anti-static plastic (Zerostat-V and Aerochamber Max), metal (Nebuchamber) anti-static spacers and metered dose inhaler [Flixotide Evohaler (EH) (pMDI)]. METHODS A randomized, double-blind, double-dummy, four-way crossover design was used. Eighteen mild to moderate asthmatics received single doses of placebo/HFA-FP 2 mg via the 280-ml Zerostat-V (ZS); 250-ml Nebuchamber (NC); 197-ml Aerochamber Max (AC); and pMDI (EH). Measurements of OUCC and EMUCC were made at baseline and 10 h after each dose. RESULTS Significant suppression of OUCC and EMUCC occurred from baseline with all three spacers, but not Evohaler (geometric mean fold suppression, 95% confidence interval): ZS, 2.74 (1.75, 4.30), P < 0.001; NC, 3.31 (1.81, 6.06), P < 0.001; AC, 4.98 (3.39, 7.31), P < 0.001; and for EH this was 1.42 (0.92, 2.21), P= 0.169 (equating to a 64, 70, 80 and 30% fall in OUCC via the ZS, NC, AC and EH devices, respectively). There were significant differences between all three spacers vs. EH. When compared with the Evohaler, the Zerostat V resulted in 48% greater suppression (P= 0.009); the Nebuchamber 57% greater suppression (P= 0.001); and the Aerochamber Max 71% greater suppression of OUCC (P < 0.001). CONCLUSION All three antistatic spacers significantly increased the relative systemic bioavailability of HFA-FP compared with the standard pMDI. [source] Effect of plastic spacer handling on salbutamol lung deposition in asthmatic childrenBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 5 2002Brian J. Lipworth Aims, To study the effects of electrostatics in a plastic spacer on the lung deposition of salbutamol in asthmatic children. Methods, Twenty-five children (5,12 years) with mild asthma were given salbutamol hydrofluoroalkane pressurized metered dose inhaler 400 µg via a 750 ml plastic spacer on separate days. Blood samples were taken for plasma salbutamol at 5, 10, 15 and 20 min after inhalation to measure lung bioavailability as a surrogate for relative lung dose. With immediate inhalation following actuation, a new rinsed spacer (NewRinsed ) was compared with a used spacer after repeated daily use (Used ), a spacer rinsed after repeated use (UsedRinsed ) and a spacer primed with benzalkonium chloride to avoid electrostatics (Primed1). In addition, spacers were evaluated using a 15 s inhalation delay following actuation with primed (PrimedDelay) and rinsed (RinsedDelay) spacers. Data were log transformed and expressed as geometric mean fold difference for the average plasma salbutamol concentration (Cav) over 20 min. Results, There were significant differences (P < 0.05) in Cav (as geometric mean fold difference and 95% CI) between Primed1 vs NewRinsed 1.92 fold (95% CI 1.15, 3.20) and between Used vs NewRinsed 1.75 fold (1.11, 2.76). There were no significant differences comparing Primed1, Used or UsedRinsed. There were also significant differences (P < 0.05) between Primed1 vs PrimedDelay 2.34 fold (1.31, 4.19), or vs RinsedDelay 3.59 fold (2.15, 5.99); and for Used vs PrimedDelay 2.14 fold (1.24, 3.69), or vs RinsedDelay 3.28 fold (2.13, 5.04). Conclusions, The relative lung dose of salbutamol from a plastic spacer may differ considerably depending on spacer handling suggesting that nonelectrostatic spacers may be the best way forward. [source] | ||||||||||