Relative bioavailability of terbutaline to the lung following inhalation, using urinary excretion

Abdelrahim, Mohamed; Assi, K.H.; Chrystyn, Henry

doi:10.1111/j.1365-2125.2010.03873.x

Cited by 44 publications

(42 citation statements)

References 7 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 30 min urinary excretion highlights the usefulness of this index as a measure of the relative bioavailability of beclometasone dipropionate to the lungs following an inhalation. The inter‐ and the intra‐individual variation is consistent with that previously reported for salbutamol [16], as well as gentamicin [19], formoterol [20], sodium cromoglicate [21] and terbutaline [22].…”

Section: Discussionsupporting

confidence: 90%

Urinary pharmacokinetic methodology to determine the relative lung bioavailability of inhaled beclometasone dipropionate

Said

Harding

Chrystyn

2012

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Urinary pharmacokinetic methodology can be used to identify the relative bioavailability to the lungs and the systemic circulation after an inhalation but has not yet been extended to corticosteroids.• Two (Qvar® and Clenil®) HFA (CFC-free) metered dose inhaler formulations of beclometasone dipropionate are now available. The recommended dose of Qvar is half that of Clenil but the two have yet to be compared. WHAT THIS STUDY ADDS• The urinary excretion of beclometasone dipropionate and its main metabolites (beclometasone-17-monopropionate and beclometasone) in the first 30 min post inhalation represents the relative bioavailability to the lungs after an inhalation.• Similarly the 24 h urinary excretion of the main metabolites can be used to identify the relative bioavailability to the systemic circulation after an inhalation.• The relative lung and systemic bioavailability between Qvar and Clenil confirms the two fold difference in their recommended doses. AIMUrinary pharmacokinetic methods have been identified to determine the relative lung and systemic bioavailability after an inhalation. We have extended this methodology to inhaled beclometasone dipropionate (BDP). METHODEthics Committee approval was obtained and all subjects gave consent. Twelve healthy volunteers received randomized doses, separated by >7 days, of 2000 mg BDP solution with (OralC) and without (Oral) 5 g oral charcoal, 10 100 mg inhalations from a Qvar® Easibreathe metered dose inhaler (pMDI) with (QvarC) and without (Qvar) oral charcoal and eight 250 mg inhalations from a Clenil® pMDI (Clenil). Subjects provided urine samples at 0, 0.5, 1, 2, 3, 5, 8, 12 and 24 h post study dose. Urinary concentrations of BDP and its metabolites, beclometasone-17-monopropionate (17-BMP) and beclometasone (BOH) were measured. RESULTSNo BDP, 17-BMP or BOH were detected in any samples post OralC dosing. Post oral dosing no BDP was detected in all urine samples and no 17-BMP or BOH was excreted in the first 30 min. Significantly more (P < 0.001) BDP, 17-BMP and BOH were excreted in the first 30 min and the cumulative 24 h urinary excretions post Qvar and Clenil compared with Oral. The mean ratio (90% confidence interval) of the 30 min urinary excretions for Qvar compared with Clenil was 231.4 (209.6, 255.7) %. CONCLUSIONThe urinary pharmacokinetic methodology to determine the relative lung and systemic bioavailability post inhalation, using 30 min and cumulative 24 h post inhalation samples, applies to BDP. The ratio between Qvar and Clenil is consistent with related clinical and lung deposition studies.

show abstract

Section: Discussionsupporting

confidence: 90%

Urinary pharmacokinetic methodology to determine the relative lung bioavailability of inhaled beclometasone dipropionate

Said

Harding

Chrystyn

2012

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

show abstract

“…A novel pharmacokinetic method that have been previously developed for Salbutamol 7 and validated for terbutaline 8 was used here to compare the different inhalation maneuvers. As mentioned before, the previously validated terbutaline pharmacokinetic method had shown that the amount of terbutaline excreted in urine 30 min post dosing is an index of the amount of terbutaline deposited in the The amount excreted 30 min and 24 h post dosing using slow and fast inhalation flows after one inhalation from healthy subject and COPD patients confirm the flow dependent dose emission property of the Turbuhaler.…”

Section: Discussionmentioning

confidence: 99%

“…On each study day subjects were allowed to have a light breakfast and no caffeine or alcohol containing drinks for at least 12 hbefore dosing. According to the novel urinary terbutaline method, 8 immediately before each study dose each subject voided their urine then provided a urine sample 30 min after the start of the first dose and cumulatively collected their urine for 24 h. The volumes of urine samples were measured and assayed for the urinary terbutaline concentration using an HPLC-fluorescence spectrophotometry. The terbutaline was extracted from the urine samples together with Bamethane (Sigma, UK) as internal standard using solid phase extraction, Isolute HCX 130 mg 10 ml XL cartridge and Oasis HLB 30 mg cartridge, then injected in the HPLC system.…”

Section: In Vivo Proceduresmentioning

confidence: 99%

Emitted dose and lung deposition of inhaled terbutaline from Turbuhaler at different conditions

Abdelrahim

2010

Respiratory Medicine

Self Cite

View full text Add to dashboard Cite

Turbuhaler has a very high resistance hence patient inhalation flow when using it would be low. The total emitted dose (TED) of 500microg terbutaline sulphate from a Bricanyl Turbuhaler was determined using a range of inhalation flows (10-60L min(-1)) with inhalation volume of 2 and 4L using a DPI sampling apparatus after one and two inhalations. The relative lung and systemic bioavailability of terbutaline from Bricanyl Turbuhaler when used by healthy subjects and COPD patients were determined after one and two inhalations at slow and fast inhalation flows using a novel urinary terbutaline pharmacokinetic method. The TED resulted from the one and two inhalations increased significantly (p<0.05) with the increase of the inhalation flow at both 2 and 4L inhalation volumes. The relative lung and systemic bioavailability after one inhalation at fast inhalation flow were significantly higher (p<0.01) than at slow inhalation flow in both healthy subjects and patients. Also the healthy subjects results were significantly higher (p<0.05) than the COPD patients after one inhalation. However after two inhalations there was no significant difference between slow and fast inhalation flow or healthy subjects and COPD patients. Hence it is essential to inhale twice and as deep and hard as possible from each dose of Turbuhaler for patients with low inspiratory flow and limited inhalation volume as they may not receive much benefit from one inhalation.

show abstract

“…The output property Y1 was the percentage of excreted dose (lung or systemic bioavailability) 6,17 . Sampling time of 0.5 hour was indicative of lung bioavailability of the inhaled drug, while 24 hour cumulative samples were representative of the amount of the systemic bioavailability of the drug 25 …”

Section: Methodsmentioning

confidence: 99%

In vitro and in vivo performance modelling and optimisation of different dry powder inhalers: A complementary study of neural networks, genetic algorithms and decision trees

et al. 2020

View full text Add to dashboard Cite

Introduction Aerosol delivery from DPIs could be affected by different factors. This study aimed to evaluate and predict the effects of different factors on drug delivery from DPIs. Methods Modelling and optimisation for both in vitro and in vivo data of different DPIs (Diskus, Turbohaler and Aerolizer) were carried out using neural networks associated with genetic algorithms and the results are confirmed using a decision tree (DT) and random forest regressor (RFR). All variables (the type of DPI, inhalation flow, inhalation volume, number of inhalations and type of subject) were coded as numbers before using them in the modelling study. Results The analysis of the in vitro model showed that Turbohaler had the highest emitted dose compared with the Diskus and the Aerolizer. Increasing flow resulted in a gradual increase in the emitted dose. Little differences between the inhalation volumes 2 and 4 litres were shown at fast inhalation flow, and interestingly two inhalations showed somewhat higher emitted doses than one‐inhalation mode with Turbohaler and Diskus at slow inhalation flow. Regarding the in vivo model, the percent of drug delivered to the lung was highly increased with Turbohaler and Diskus in healthy subjects where continuous contour lines were observed. The Turbohaler showed increased lung bioavailability with the two‐inhalation modes, the Diskus showed a nearly constant level at both one and two inhalations at slow inhalation. The Turbohaler and Aerolizer showed little increasing effect moving from one to two inhalations at slow inhalation. Conclusions Modelling of the input data showed a good differentiating and prediction power for both in vitro and in vivo models. The results of the modelling refer to the high efficacy of Diskus followed by Turbohaler for delivering aerosol. With two inhalations, the three DPIs showed an increase in the percent of drug excreted at slow inhalations.

show abstract

Relative bioavailability of terbutaline to the lung following inhalation, using urinary excretion

Cited by 44 publications

References 7 publications

Urinary pharmacokinetic methodology to determine the relative lung bioavailability of inhaled beclometasone dipropionate

Urinary pharmacokinetic methodology to determine the relative lung bioavailability of inhaled beclometasone dipropionate

Emitted dose and lung deposition of inhaled terbutaline from Turbuhaler at different conditions

In vitro and in vivo performance modelling and optimisation of different dry powder inhalers: A complementary study of neural networks, genetic algorithms and decision trees

Contact Info

Product

Resources

About