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- Adolfsson, L. E., et al.
(author)
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Short-term safety and tolerability of double-dose salmeterol/fluticasone propionate in adult asthmatic patients
- 2005
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In: Clin Drug Investig. - 1173-2563. ; 25:4, s. 231-41
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Journal article (peer-reviewed)abstract
- INTRODUCTION: The incidence of asthma exacerbations in patients receiving salmeterol/fluticasone propionate (Seretidetrade mark or Advair((R))) is low. However, when asthma control deteriorates, clinicians may instruct patients to double the dose of their inhaled corticosteroid medication for a short period. The purpose of this study was to demonstrate that doubling the dose of Seretidetrade mark for a period of 2 weeks in subjects with persistent asthma is safe and well tolerated. METHODS: This randomised, double-blind, parallel-group study was conducted in primary-care centres. Adults with a post-bronchodilator forced expiratory volume in 1 second (FEV(1)) of >/=70% predicted were stratified to receive a single dose of Seretidetrade mark 50mug/100mug, 50mug/250mug or 50mug/500mug twice daily from a Diskustrade mark inhaler for a 4-week run-in period, dependent on the dose of inhaled corticosteroid on entry. Subjects were then randomised to receive either an extra inhalation of the same dose of Seretidetrade mark received during the run-in (double dose) or an inhalation of matching placebo (single dose) for 14 days in a 2 : 1 ratio. Subjects were asked to record any adverse events, morning and evening heart rate (HR), peak flow and relief medication use in daily record cards. The primary endpoint was tremor as perceived by the subject. Clinic evaluations included HR, 12-lead ECG, and potassium and glucose levels. RESULTS: 110 and 208 subjects received single- and double-dose Seretidetrade mark, respectively. Only one subject experienced tremor. This was classified as mild and occurred in a subject receiving double-dose Seretidetrade mark (50mug/100mug). There was no difference between the treatment groups in the incidence of tremor (difference <1%; 95% CI -6, 8). Other salmeterol-related adverse events (palpitations, muscle cramps and headache) and fluticasone propionate-related events (oral candidiasis and hoarseness) occurred in a similar percentage of subjects in each treatment group. The treatment differences for morning and evening HR measurements showed small differences between the two groups (<2 beats/min). The adjusted mean treatment difference (double dose - single dose) in morning HR was 1.1 beats/min (95% CI 0.2, 2.0) and evening HR was 0.9 beats/min (95% CI 0.1, 1.7). Seven percent of subjects receiving single-dose Seretidetrade mark and 8% receiving double-dose Seretidetrade mark had a QTc change from baseline in the interval 30-59 msec. No increases above 59 msec were seen in either group. There were no clinically significant changes from baseline for potassium levels. Two percent of subjects in the single dose and <1% in the double-dose group had a change from a non-clinically significant baseline blood glucose assessment to a clinically significant abnormality at the end of treatment. CONCLUSION: In circumstances in which a physician may be considering doubling the dose of Seretidetrade mark for a short period of time in adult asthmatics, this study demonstrates that doubling the dose for a period of 2 weeks is safe and well tolerated.
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| 2. |
- Erlinge, David, et al.
(author)
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Uridine triphosphate (UTP) is released during cardiac ischemia
- 2005
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In: Int J Cardiol. - : Elsevier BV. - 0167-5273. ; 100:3, s. 427-33
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Journal article (peer-reviewed)abstract
- BACKGROUND: Extracellular uridine triphosphate (UTP) stimulates vasodilatation, automaticity in ventricular myocytes and release of tissue-plasminogen activator (t-PA), indicating that UTP may be important in cardiac regulation. We took advantage of a recently developed quantitative assay for UTP to test the hypothesis that UTP is released in the circulation during cardiac ischemia. METHODS: In ten pigs, a balloon catheter in the left anterior descending artery was introduced to induce ischemia. Samples were collected from the coronary sinus. Blood flow in the coronary sinus was assessed by a Doppler velocity transducer. RESULTS: Plasma UTP levels increased early during ischemia and early after reperfusion (by 257+/-100 and 247+/-72%, p<0.05). Cardiac blood flow, ventricular arrhythmias and t-PA release were markedly increased at the same time points. In contrast, after 30 min, a second period of ischemia did not result in any significant increase of UTP or blood flow. Furthermore, ventricular arrhythmias were less frequent. UTP levels correlated with ventricular arrhythmia and blood flow. Similar results were found for ATP. CONCLUSION: For the first time we have shown that UTP is released during cardiac ischemia. UTP released during ischemia may stimulate blood flow, arrhythmia and t-PA release.
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