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非诺特罗干粉对哮喘患者的支气管扩张、致震颤、心血管及低钾血症作用的研究。

Studies on the bronchodilator, tremorogenic, cardiovascular and hypokalaemic effects of fenoterol dry powder in asthma.

作者信息

Bauer K G, Kaik B, Sertl K, Kaik G A

机构信息

University of Vienna Medical School, Department of Internal Medicine I, Division of Clinical Pharmacology, Vienna, Austria.

出版信息

Br J Clin Pharmacol. 1993 Oct;36(4):285-92. doi: 10.1111/j.1365-2125.1993.tb00366.x.

Abstract
  1. The airway and tremor response and cardiovascular and hypokalaemic effects of single and cumulative doses of fenoterol given by dry powder capsules (DPC) and by metered dose inhaler (MDI) were studied in asthmatics in two randomized, crossover trials. 2. Single doses of fenoterol DPC and MDI (0.2 mg, 0.4 mg), investigated in 24 subjects, produced similar, dose-dependent increases in FEV1. Fenoterol DPC caused less tremor response and less hypokalaemic effects than fenoterol MDI. 3. Cumulative doses of fenoterol DPC and MDI (0.2, 0.6, 1.4, 3.0, 6.2 mg), investigated in 12 subjects, produced a comparable bronchodilatation (mean maximum increase in FEV1 was 0.53 +/- 0.06/0.52 +/- 0.081 for DPC/MDI) and a similar, dose-dependent rise in heart rate (35 +/- 3.81/41 +/- 2.25 beats min(-1)). The rise in tremor and the fall in plasma potassium were smaller after DPC than after MDI. The mean maximum changes were 51.58 +/- 6.41/95.83 +/- 6.75 cm s(-2) for tremor and -0.68 +/- 0.09/-0.96 +/- 0.10 mmol l(-1) for potassium. 4. Our findings may result from a difference in the pharmacokinetics of the dry powder and the aerosol formulation, particularly differences in distribution and absorption. 5. In conclusion, fenoterol DPC used in low therapeutic doses (0.2,0.4 mg), is preferable to the MDI. Fenoterol DPC used as rescue medication in high cumulative doses, do not suggest a greater safety margin than the MDI and the same restrictions should be considered for the fenoterol dry powder formulation as suggested for the MDI.
摘要
  1. 在两项随机交叉试验中,对哮喘患者研究了通过干粉胶囊(DPC)和定量吸入器(MDI)给予单次和累积剂量非诺特罗的气道和震颤反应以及心血管和低钾血症效应。2. 在24名受试者中研究的单次剂量非诺特罗DPC和MDI(0.2毫克、0.4毫克),使第一秒用力呼气容积(FEV1)产生了相似的剂量依赖性增加。非诺特罗DPC引起的震颤反应和低钾血症效应比非诺特罗MDI少。3. 在12名受试者中研究的非诺特罗DPC和MDI的累积剂量(0.2、0.6、1.4、3.0、6.2毫克),产生了相当的支气管扩张作用(DPC/MDI的FEV1平均最大增加量为0.53±0.06/0.52±0.081)以及相似的剂量依赖性心率升高(35±3.81/41±2.25次/分钟)。DPC给药后震颤增加和血浆钾下降比MDI后更小。震颤的平均最大变化为51.58±6.41/95.83±6.75厘米/秒²,钾的平均最大变化为-0.68±0.09/-0.96±0.10毫摩尔/升。4. 我们的发现可能源于干粉和气雾剂制剂药代动力学的差异特别是分布和吸收方面的差异。5. 总之,低治疗剂量(0.2、0.4毫克)使用的非诺特罗DPC比MDI更可取。高累积剂量用作急救药物的非诺特罗DPC,并未显示出比MDI有更大的安全边际,并且对于非诺特罗干粉制剂应考虑与MDI相同的限制。

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1
Studies on the bronchodilator, tremorogenic, cardiovascular and hypokalaemic effects of fenoterol dry powder in asthma.
Br J Clin Pharmacol. 1993 Oct;36(4):285-92. doi: 10.1111/j.1365-2125.1993.tb00366.x.
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Pharmacodynamic effects of inhaled dry powder formulations of fenoterol and colforsin in asthma.
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