Lindström Maria, Svensson Jan Olof, Meurling Lennart, Svartengren Katharina, Anderson Martin, Svartengren Magnus
Division of Occupational Medicine, Department of Public Health Science, Karolinska Institutet, Stockholm SE-171 76, Sweden.
Respir Med. 2004 Jan;98(1):9-16. doi: 10.1016/j.rmed.2003.08.010.
When the expected effect of an inhaled drug is not achieved, the cause could be poor inhalation technique and consequently a low pulmonary dose. A simple in vivo test to evaluate the pulmonary dose would be a benefit. This study evaluates the relative and systemic bioavailability following inhalation of nebulized sodium cromoglycate (SCG) in healthy subjects. Blood samples were collected during 240 min and urine was collected in two portions, up to 6 h post-inhalation. Two exposures were performed and comparisons based on the quantification of drug in plasma and urine by a high-performance liquid chromatography (HPLC) procedure were done. In one of the exposures, a pulmonary function test was performed to study if an expected effect of increased absorption could be detected. There was a good correlation between the two exposures shown in the plasma concentrations, but not in the urine analyses. The forced exhaled volume manoeuvres were associated with a higher Cmax and plasma concentrations up to 60 min post-inhalation (P<0.01). This effect was not detected in the urine analyses. We conclude that this pharmacokinetic method with inhaled SCG and plasma analyses could be used to evaluate individual inhalation technique. The HPLC method used was rapid and had adequate sensitivity.
当吸入药物未达到预期效果时，原因可能是吸入技术不佳，进而导致肺部剂量较低。一项评估肺部剂量的简单体内试验将很有帮助。本研究评估了健康受试者雾化吸入色甘酸钠（SCG）后的相对生物利用度和全身生物利用度。在240分钟内采集血样，并在吸入后6小时内分两部分收集尿液。进行了两次暴露，并通过高效液相色谱（HPLC）程序对血浆和尿液中的药物进行定量分析来进行比较。在其中一次暴露中，进行了肺功能测试，以研究是否能检测到预期的吸收增加效果。血浆浓度显示两次暴露之间有良好的相关性，但尿液分析中没有。用力呼气量操作与吸入后60分钟内较高的Cmax和血浆浓度相关（P<0.01）。在尿液分析中未检测到这种效果。我们得出结论，这种吸入SCG和血浆分析的药代动力学方法可用于评估个体吸入技术。所使用的HPLC方法快速且具有足够的灵敏度。
