Auty R M, Brown K, Neale M G, Snashall P D
Pharmaceutical Division, Science and Technology Laboratories, Loughborough, Leics., UK.
Br J Dis Chest. 1987 Oct;81(4):371-80. doi: 10.1016/0007-0971(87)90186-0.
Sodium cromoglycate deposition has been studied following delivery of the drug by inhalation to six normal volunteers and two groups of ten patients using the Spinhaler. Plasma concentrations of the drug, and its urinary excretion have been related to the inhalation technique used for its delivery. An early peak concentration of sodium cromoglycate occurred in the plasma, thereafter the plasma concentration declined mono- or bi-exponentially with a terminal T1/2 of approximately 100 minutes in both patients and normal subjects. There was a marked between-subject variability in the plasma concentrations of sodium cromoglycate achieved, and in the areas under the plasma concentration-time curves of the drug. This reflects the variability between subjects in the amount of drug delivered to the respiratory tract. Most of this variability was due to differences in inhalation technique particularly with regard to inspiratory flow rate achieved and duration of breath-holding after inhalation. Thus careful instruction of patients is required to derive optimal dosing with sodium cromoglycate. It is recommended that patients inhale through the Spinhaler as rapidly as possible and then breath-hold for 10 seconds. These data provide a valuable background against which to study the relationship between the disposition of sodium cromoglycate, its site of action and its efficacy.
已对6名正常志愿者和两组各10名患者使用Spinhaler吸入器吸入色甘酸钠后的沉积情况进行了研究。该药物的血浆浓度及其尿排泄量与给药时使用的吸入技术相关。血浆中色甘酸钠出现早期峰值浓度，此后血浆浓度在患者和正常受试者中均呈单指数或双指数下降，终末半衰期约为100分钟。所达到的色甘酸钠血浆浓度以及该药物血浆浓度-时间曲线下的面积在受试者之间存在显著差异。这反映了受试者之间输送到呼吸道的药物量的差异。这种差异大多是由于吸入技术的不同，尤其是吸气流速和吸入后屏气时间的差异。因此，需要对患者进行仔细指导，以实现色甘酸钠的最佳给药。建议患者尽可能快地通过Spinhaler吸入，然后屏气10秒。这些数据为研究色甘酸钠的处置、作用部位及其疗效之间的关系提供了有价值的背景。
