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- Bondesson, Eva, et al.
(författare)
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Exhaled breath condensate-site and mechanisms of formation
- 2009
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Ingår i: Journal of Breath Research. - : IOP Publishing. - 1752-7163 .- 1752-7155. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Exhaled breath condensate (EBC) analysis is a promising tool for diagnosis and management of pulmonary diseases. Its clinical usefulness is still limited however due to unresolved issues around e. g. reproducibility, anatomical site of origin of EBC solutes and mechanisms of EBC formation. To gain some knowledge on these issues, three different airway deposition patterns of an aqueous aerosol containing technetium-99m were studied in eight healthy non-smoking subjects. EBC was collected 20 min after each radioaerosol administration and analyzed for gamma radiation and electrolytes. Radioaerosol deposition in preferentially central lung compared with preferentially peripheral lung resulted in 3.8 times higher EBC radioactivity. EBC concentrations of Na+ and K+ correlated significantly indicating dilution by water vapor to be a major source of variability. Since Na+/K+- and Na+/S2--concentration ratios, but not Na+/Cl--or Na+/Ca2+-, were comparable to those previously reported for alveolar lining fluid (ALF), some mechanisms other than dilution are likely also to be involved. In conclusion, our findings indicate that EBC derives mainly from the central airways, that the electrolyte composition of EBC does not consistently reflect that of ALF, and that EBC concentrations of electrolytes are determined not only by ALF dilution with water vapor but also by other mechanisms.
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- Bondesson, Eva, et al.
(författare)
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In vitro and in vivo aspects of quantifying intrapulmonary deposition of a dry powder radioaerosol.
- 2002
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Ingår i: International Journal of Pharmaceutics. - 1873-3476. ; 232:1-2, s. 149-156
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary delivery of pharmaceutical aerosols can be quantified using gamma scintigraphy. Technetium-99m, the most commonly used radionuclide in scintigraphic studies, cannot be incorporated into the drug molecule and, therefore, may be distributed differently from the drug itself, particularly if the drug is presented as a solid in a liquid suspension or as a dry powder formulation. This study demonstrated the importance of using conditions relevant to the in vivo situation in the in vitro characterisation of a dry powder aerosol of 99mTc-labelled lactose. The influence of inspiratory flow on the distribution of aerosol within the lungs was investigated in eight healthy subjects who inhaled the 99mTc-labelled lactose at four flows (30,40,60 and 80 l/min). No differences in penetration index (PI) or count density distribution of radioactivity were seen, indicating that regional distribution of aerosol in healthy airways was insensitive to differences in the inspiratory effort exerted by the subject while inhaling the experimental dry powder radioaerosol.
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- Bondesson, Eva, et al.
(författare)
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Planar gamma scintigraphy - points to consider when quantifying pulmonary dry powder aerosol deposition
- 2003
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Ingår i: International Journal of Pharmaceutics. - 1873-3476. ; 251:1-2, s. 33-47
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Tidskriftsartikel (refereegranskat)abstract
- Methodological aspects of planar gamma scintigraphy used to quantify pulmonary aerosol deposition were investigated using an experimental dry powder formulation. Particles of micronized salbutamol sulphate were labelled with technetium-99m and admixed to an ordered mixture of unlabelled micronized salbutamol sulphate and larger carrier particles of lactose. The radioaerosol was administered to 24 healthy subjects, 12 in each of two consecutive, similarly designed studies. Pulmonary deposition was determined using two methods: repeated planar imaging, and pharmacokinetic assessments following charcoal co-administration to prevent gastrointestinal salbutamol absorption. After due consideration had been taken to ensure appropriate radiolabelling, image acquisition and processing procedures, a scintigraphic estimate of 26.2% (24.2-28.4%) was obtained, which did not significantly differ from the pharmacokinetic estimate of 26.4% (24.4-28.7%). In summary, pre-study validation of the radiolabelling technique, quality control of radioaerosols produced during the study, correction for re-distribution of radiolabel from the lungs, selection of regions of interest, assessment of lung contours, correction for tissue attenuation of gamma rays and establishment of the actual recovery of radioactivity in the scintigraphic measurements could potentially affect the accuracy of the scintigraphic estimate of pulmonary deposition and, thus, should be carefully considered in the design or evaluation of any such study.
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- Bondesson, Eva, et al.
(författare)
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Site of deposition and absorption of an inhaled hydrophilic solute
- 2007
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 1365-2125 .- 0306-5251. ; 63:6, s. 722-731
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Tidskriftsartikel (refereegranskat)abstract
- Aims To characterize the absorption kinetics and bioavailability of an inhaled hydrophilic solute deposited at various sites within the airways. Methods Nine healthy nonsmokers received one intravenous, one oropharyngeal and two pulmonary doses of technetium-99 m-labelled diethylene triamine pentaacetic acid (Tc-99m-DTPA) in an open and crossover fashion. Pulmonary doses were administered as nebulized large and fine droplet-sized aerosols by Pari and UltraVent nebulizers at fairly rapid and slow inhalation flows, respectively. Plasma concentration-time profiles and 24 h urinary excretion of radioactivity were determined. One dose of Tc-99m-labelled Nanocoll, as a marker of mucociliary clearance (MCC), was also administered by Pari for similar lung deposition as the Tc-99m-DTPA and followed by repeated chest gamma-imaging. Results Intrapulmonary deposition patterns of Tc-99m-DTPA differed significantly (the mean ratio of penetration index (Pari : UltraVent) was 76% with 95% CI 63%, 91%). However, no differences in rate or extent of Tc-99m-DTPA absorption were detected. Mean absorption time was 1.8 h (mean difference (Pari-UltraVent): -0.1 h with 95% CI -0.6 h, 0.3 h) and the bioavailability was 70% (mean ratio (Pari : UltraVent): 101% with 95% CI 90%, 115%). The pulmonary elimination half-life of Tc-99m-Nanocoll (8 h and 45 min) was significantly longer than that of Tc-99m-DTPA (less than 2 h). The oral bioavailability of Tc-99m-DTPA was estimated to be 3.1%. Conclusions The main elimination pathway of the inhaled hydrophilic solute Tc-99m-DTPA from the lungs is trans-epithelial absorption. Despite different intrapulmonary radioaerosol deposition patterns, as verified by gamma scintigraphy, no differences in Tc-99m-DTPA absorption kinetics or bioavailability were detected.
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- Reza Felix, Mariana, et al.
(författare)
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Bone Scan Index and Progression-free Survival Data for Progressive Metastatic Castration-resistant Prostate Cancer Patients Who Received ODM-201 in the ARADES Multicentre Study
- 2016
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Ingår i: European Urology Focus. - : Elsevier BV. - 2405-4569. ; 2:5, s. 547-552
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Tidskriftsartikel (refereegranskat)abstract
- Background ODM-201, a new-generation androgen receptor inhibitor, has shown clinical efficacy in prostate cancer (PCa). Quantitative methods are needed to accurately assess changes in bone as a measurement of treatment response. The Bone Scan Index (BSI) reflects the percentage of skeletal mass a given tumour affects. Objective To evaluate the predictive value of the BSI in metastatic castration-resistant PCa (mCRPC) patients undergoing treatment with ODM-201. Design, setting, and participants From a total of 134 mCRPC patients who participated in the Activity and Safety of ODM-201 in Patients with Progressive Metastatic Castration-resistant Prostate Cancer clinical trial and received ODM-201, we retrospectively selected all those patients who had bone scan image data of sufficient quality to allow for both baseline and 12-wk follow-up BSI-assessments (n = 47). We used the automated EXINI bone BSI software (EXINI Diagnostics AB, Lund, Sweden) to obtain BSI data. Outcome measurements and statistical analysis We used the Cox proportional hazards model and Kaplan-Meier estimates to investigate the association among BSI, traditional clinical parameters, disease progression, and radiographic progression-free survival (rPFS). Results and limitations In the BSI assessments, at follow-up, patients who had a decrease or at most a 20% increase from BSI baseline had a significantly longer time to progression in bone (median not reached vs 23 wk, hazard ratio [HR]: 0.20; 95% confidence interval [CI], 0.07–0.58; p = 0.003) and rPFS (median: 50 wk vs 14 wk; HR: 0.35; 95% CI, 0.17–0.74; p = 0.006) than those who had a BSI increase >20% during treatment. Conclusions The on-treatment change in BSI was significantly associated with rPFS in mCRPC patients, and an increase >20% in BSI predicted reduced rPFS. BSI for quantification of bone metastases may be a valuable complementary method for evaluation of treatment response in mCRPC patients. Patient summary An increase in Bone Scan Index (BSI) was associated with shorter time to disease progression in patients treated with ODM-201. BSI may be a valuable method of complementing treatment response evaluation in patients with advanced prostate cancer.
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