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As part of a development program to offer alternatives to chlorofluorocarbon (CFC) containing metered‐dose inhalers, beclomethasone dipropionate has been formulated in a CFC‐free system at three strengths: 50, 100, and 200 μg/actuation ex valve. To measure serum levels and dose proportionality of the beclomethasone derived from beclomethasone dipropionate, 13 mild to moderate asthmatic patients received a single dose of eight inhalations from each strength according to a double‐blind crossover design. Seven patients were studied over 4 h and six patients over 12 h. For the total doses of 400, 800, and 1600 μg studied over 12 h, Cmax and AUC increased in a ratio of 1:1·8:3·1. A good correlation was seen between the fine‐particle mass delivered and the in vivo performance of the three strengths. From a clinical point of view, the predictable increases in serum levels with an increase in dose will permit the clinician to effectively titrate a patient with this product. © 1997 John Wiley & Sons, Ltd.

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.

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