The fate of3H-terbutaline sulphate administered to man as an aerosol

Nilsson, Helena; Simonsson, Bo G.; Ström, B

doi:10.1007/bf00561542

Cited by 25 publications

(6 citation statements)

References 9 publications

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“…Over 80% of an inhaled dose from a metered-dose inhaler may be deposited in the oropharnyx and subsequently swallowed (Davies, 1975;Newman et al, 1981). Kung and coworkers (1987) however, showed that mouthwashing has no effect on the metabolic response to inhaled salbutamol although only 24% of the total dose was recovered in the wash. Pharmacokinetic studies with metered-dose inhalers show that peak plasma levels occur within 1 and 3 h following administration of terbutaline and salbutamol respectively (Walker etal., 1972;Nilson et al, 1976). The plasma cAMP responses in our study (Figure 7) showed a significant increase after the first dose of salbutamol (100 ,ug).…”

Section: Discussionsupporting

confidence: 47%

Beta‐adrenoceptor responses to high doses of inhaled salbutamol in patients with bronchial asthma.

Lipworth

Clark

Dhillon

et al. 1988

Brit J Clinical Pharma

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1 Fourteen asthmatics (mean ± s.e. mean baseline FEV1 62 ± 6% of predicted) were given cumulative doubling doses of salbutamol by metered-dose inhaler as follows: 100 ,ug, 200 pg, 500 pg, 1000 pug, 2000 ,ug, 4000 ,ug. 2 Airways, tremor, haemodynamic and cyclic AMP responses were measured at each dose increment (made every 20 min). 3 There was a linear log dose-response relationship for each airways parameter (FEV1, VC, sGaw, FEF 50%). The plateau in the dose-response curve was not reached within our dose range. These changes were also mirrored in cyclic AMP responses. 4 There was a wide range in maximum airways response expressed in terms of absolute increase over baseline (95% confidence intervals: AFEV1 667-1483 ml; A VC 689-1695 ml; A sGaw 0.92-4.50 s-1 kPa-1; A FEF 50% 0.94-2.15 1 s-). Patients with a lower baseline showed a greater response in terms of percent increase in FEV1 (r = -0.83, P < 0.001). There was however, no correlation between baseline airway calibre and the dose required for maximum bronchodilatation.5 There were objective increases (mean ± s.e. mean) in both heart rate (maximum A HR of 14 ± 5 beats min-' at 4000 ,ug) and tremor power (maximum A Tr of 115 ± 44% at 2000 ,ug). These were not dose limiting side-effects as subjective symptoms were infrequent at higher doses. 6 Higher than conventional doses of salbutamol given by metered-dose inhaler may produce a distinct improvement in airways response without significant side-effects. There is a wide individual variation in airways response to inhaled salbutamol, although most patients required higher doses to achieve maximal bronchodilatation. The severity of asthma does not however predict the dose required for maximum airways response.

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Section: Discussionsupporting

confidence: 47%

Beta‐adrenoceptor responses to high doses of inhaled salbutamol in patients with bronchial asthma.

Lipworth

Clark

Dhillon

et al. 1988

Brit J Clinical Pharma

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“…In direct procedures involve use of direct chemical detection and tritium or 14C-labeled (32-agonists. Intra-and extrabronchial deposition has been studied using pharmacodynamic measurements of con centrations in mouth washings, stool, urine and blood [Davies, 1978;Laros et al, 1977;Nilsson et al, 1976]. No micron ized drugs were used for this but the la beled p2-agonists were administered in a so lution, with the exception of Moren [1982] who used micronized drugs to estimate the deposition pattern with mouth washings and Kim et al [1987] who used oropharyn geal models.…”

Section: Introductionmentioning

confidence: 99%

New Method for Easy Labeling of Beta-2-Agonists in the Metered Dose Inhaler with Technetium 99 m

Köhler

Fleischer²,

Matthys³

1988

Respiration

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The actual deposition pattern of micronized drugs from metered dose inhalers (MDI) is incompletely known because there are no methods available to label the drugs (β₂-agonists) with γ-emitters. Indirect measurements of the distribution of the drug in man differed greatly due to the method used. Our method uses the better solubility of ^99mTcO^-₄ in the β₂-agonist-micronized drug in relation to the propellant with surfactant. The principle is to extract the ^99mTcO^-₄ from the original water phase into the liquid phase of the propellant with ethyl methyl ketone. For labeling the micronized drug particles, the original MDI must be cooled to -60 °C and some labeled propellant (including surfactant) with high specific activity of ^99mTcO^-₄ is added through an aperture in the bottom of the container. The aperture is sealed with a screw. After rewarming the MDI, more than 90% of the added ^99mTcO^-₄ is dissolved in the β₂-agonist-micronized drug in relation to its volume. This is proved by comparing the distribution of the radioactivity component with chemical analysis. The pattern of deposition of both MDIs -placebo and β₂-agonist-micronized drug – was shown to be similar in healthy volunteers. With a labeled MDI a preliminary study with 2 different inhaling maneuvers was performed in 7 volunteers: inhaling from residual volume after a pause of 2 s the intrabronchial deposition was 18.7%, and inhaling at 50% of vital capacity maneuver the intrabronchial deposition was 33.0%. The data obtained with actual measurement of the inhaled drug from MDI suggest greater intrabronchial deposition than was assumed before in the literature.

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“…Filter paper blood spot measurements were made using the glucose oxidase method of Wakelin et al 3 Sixteen samples of 25-40 ml venous blood from…”

Section: Methodsmentioning

confidence: 99%

“…A considerable proportion of the dose is deposited in the mouth and pharynx.1 2 Even when used correctly the proportion of the drug administered that reaches the lower respiratory tract is about 5 to 10%. 3 Attempts have been made to design delivery systems for administering aerosol drugs that overcome the problems of co-ordination and oral deposition.4 5 It is possible to decrease oral deposition by attaching tubes of various lengths and diameters to the activator6 allowing further evaporation of the aerosol vapour after the initial flash of propellent liquid and by reducing initial droplet velocity.7 Incorporating an inhalation valve into the system allows the patient to separate inhalation from activation thereby overcoming the problem of co-ordination often encountered by asthmatic children. This study was designed to compare a conventional aerosol delivery system alone delivering a p 2 stimulant with one attached to an extension tube with an inhalation valve for asthmatic children.…”

mentioning

confidence: 99%

Assessment of a new device for delivering aerosol drugs to asthmatic children.

Hodges¹,

Milner²,

Stokes³

1981

Archives of Disease in Childhood

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SUMMARY A new device, known as the aerochamber, for delivering aerosol drugs was compared with a standard aerosol inhaler in asthmatic children aged between 5 years 3 months and 13 years 10 months. The study was conducted under doubleblind conditions using fenoterol, a 3 2 stimulant, as the active agent and a placebo. Response to treatment was assessed by measuring the peak expiratory flow rate before and after each inhaler. Seven of 10 children had greater mean improvements in peak expiratory flow rates when receiving the active drug from the aerochamber. The aerochamber offers a method for administering a whole range of canistered packaged drugs to children unable to use the standard inhalers.Conventional pressurised aerosol devices administering metered doses of bronchodilator drugs present certain problems to the young asthmatic child. Co-ordinating activation of the aerosol with inspiration is the main difficulty, and often results in little of the active agent getting to its site of action. A considerable proportion of the dose is deposited in the mouth and pharynx.1 2 Even when used correctly the proportion of the drug administered that reaches the lower respiratory tract is about 5 to 10%.3Attempts have been made to design delivery systems for administering aerosol drugs that overcome the problems of co-ordination and oral deposition.4 5 It is possible to decrease oral deposition by attaching tubes of various lengths and diameters to the activator6 allowing further evaporation of the aerosol vapour after the initial flash of propellent liquid and by reducing initial droplet velocity.7 Incorporating an inhalation valve into the system allows the patient to separate inhalation from activation thereby overcoming the problem of co-ordination often encountered by asthmatic children. This study was designed to compare a conventional aerosol delivery system alone delivering a p 2 stimulant with one attached to an extension tube with an inhalation valve for asthmatic children. The attachment is known as the aerochamber. MethodChildren between ages 5 and 14 years with perennial asthma who required regular daily a 2 stimulantssuch as salbutamol-for the control of asthma were entered into the trial. Each child was given two standard metered dose inhalers, one delivering a placebo, the other 0. 2 mg fenoterol, a ,B 2 stimulant, per activation. The inhalers were labelled A and B under double-blind conditions. The new aerochamber device was attached to either inhaler A or inhaler B. The trial inhalers were used at a set time each day when the child would normally inhale a P 2 stimulant for relief of wheezing. For the rest of the day the children received their regular treatment, but no P 2 stimulant was given during the 4 hours before using the inhalers. The inhalers were always used in a set order, A first followed by B. Before using aerosol A each child recorded the best of three peak expiratory flow efforts using a mini Wright peak flow meter. The child then took two puffs from aerosol A and recorded the peak expir...

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The fate of3H-terbutaline sulphate administered to man as an aerosol

Cited by 25 publications

References 9 publications

Beta‐adrenoceptor responses to high doses of inhaled salbutamol in patients with bronchial asthma.

Beta‐adrenoceptor responses to high doses of inhaled salbutamol in patients with bronchial asthma.

New Method for Easy Labeling of Beta-2-Agonists in the Metered Dose Inhaler with Technetium 99 m

Assessment of a new device for delivering aerosol drugs to asthmatic children.

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