Harrison L I, Cline A, Wells T M, Jacobson J P, Cooper K M, Chang S F, Nelson J R, Ekholm B P, Morganroth J
Department of Drug Metabolism, 3M Pharmaceuticals, St. Paul, Minnesota 55144-1000, USA.
Ther Drug Monit. 1996 Jun;18(3):240-4. doi: 10.1097/00007691-199606000-00004.
The objective of this study was to determine if salbutamol was absorbed from a new salbutamol sulfate chlorofluorocarbon (CFC)-free metered-dose inhaler (MDI). Measurement of HFA-134a, the CFC-free propellant, was included to provide proof of delivery of this MDI. Eight healthy men received two inhalations (90 micrograms salbutamol base equivalents per inhalation ex adapter) from the CFC-free inhaler (MDI A) in period 1 and from a reference CFC inhaler (MDI V) in period 2. Eight postdose samples were collected for the determination of salbutamol serum levels over a 4-h period. Salbutamol levels were not quantifiable in most samples. Four subjects given MDI A and two given MDI V had a few transient salbutamol levels, which occurred in the first hour after dosing, within a narrow range of 1-2 ng/ml and close to the lower limit of detection (1 ng/ml). No pharmacokinetic analyses were possible. Blood samples were also collected after MDI A for propellant quantitation. HFA-134a levels were seen in all subjects, verifying absorption. We conclude that the transient salbutamol serum levels can be attributed to the two-inhalation dose and not to either propellant system.
本研究的目的是确定沙丁胺醇是否能从一种新型的不含氯氟烃(CFC)的硫酸沙丁胺醇定量吸入器(MDI)中被吸收。对不含CFC的推进剂HFA-134a进行测量,以证明该MDI的药物递送情况。8名健康男性在第1阶段从不含CFC的吸入器(MDI A)吸入两次(每次从适配器喷出的沙丁胺醇碱当量为90微克),在第2阶段从对照CFC吸入器(MDI V)吸入两次。在4小时内采集8份给药后样本,用于测定血清中沙丁胺醇水平。大多数样本中的沙丁胺醇水平无法定量。给予MDI A的4名受试者和给予MDI V的2名受试者有一些短暂的沙丁胺醇水平,出现在给药后的第1小时内,范围较窄,为1 - 2纳克/毫升,接近检测下限(1纳克/毫升)。无法进行药代动力学分析。在使用MDI A后还采集了血样用于推进剂定量。所有受试者均检测到HFA-134a水平,证实有吸收。我们得出结论,短暂的血清沙丁胺醇水平可归因于两次吸入剂量,而非任何一种推进剂系统。