Comparative efficacy and potency of ipratropium via Turbuhaler and pressurized metered-dose inhaler in reversible airflow obstruction

Abstract

Ipratropium bromide (IB), typically delivered by pressurized metered dose inhaler (pMDI), is used to treat patients with reversible airways obstruction. Use of the pMDI, unlike the Turbuhaler® (TH), demands co-ordination of actuation with inspiration for efficient use. Two studies were carried out to compare the relative efficacy and potency of IB delivered by TH or pMDI.Both studies were of a randomized, double-blind and cross-over design. For the efficacy study, 15 patients received a cumulative dose of 160 µg IB via TH or pMDI as doses of 20, 20, 40 and 80 µg at 45 min intervals on two days. Forced expiratory volume in one second (FEV1) was measured prior to and 40 min after dosing. For the potency study, 33 patients received 10, 20 or 40 µg of IB via TH, 20 µg IB via pMDI, or placebo, on five days. FEV1 was recorded prior to and 15-360 min after dosing.For the efficacy study, there was no difference in FEV1 response to a cumulative dose of IB via pMDI and TH. More than 80% of the maximum effect was seen at the lowest dose (20 µg of IB). Regarding the potency study, the FEV1 response to 20 µg IB administered via pMDI was similar to that of 10 µg via TH; 20 µg via TH was significantly more effective than 20 µg via pMDI (p<0.05).In conclusion, the efficacy study showed that maximum FEV1 occurred at low doses of IB, negating any opportunity to identify differences between devices. The potency study indicated that the 10 µg dose via TH was of similar efficacy to the 20 µg dose via pMDI, confirming an efficacy ratio of 1.5-2.0:1 for the TH device. Eur Respir J 1997; 10: 1824-1828 The controversy surrounding β 2 -agonist bronchodilators has led to a renewed interest in the anticholinergic bronchodilator ipratropium bromide (IB) which has been available for about 20 yrs and has a good safety profile. IB is used to treat patients with reversible airways obstruction, e.g. patients with chronic obstructive pulmonary disease (COPD) [1], elderly patients with asthma [2], and patients still symptomatic despite treatment with β 2 -agonists [3]. Typically, delivery is by pressurized metered-dose inhaler (pMDI); however, use of the pMDI, unlike the Turbuhaler® (TH) (Astra Draco AB, Lund, Sweden), demands co-ordination of actuation with inspiration for efficient use [4]. Chlorofluorocarbons (CFCs), which act as the propellant gas in most pMDIs, deplete the ozone layer and their use will have ceased by the end of the century. As an alternative, inspiratory flow-driven dry powder devices have been developed. Their advantages include ease of use as well as lack of local irritation and paradoxical bronchoconstriction secondary to the propellants/surfactants [5,6]. TH, a multidose dry powder inhaler, contains pure drug (budesonide or terbutaline) or IB and lactose as diluent; an inspiratory flow of as low as 30 L·min -1 is sufficient for efficacy from the device [7]. Previous studies with other drugs have shown the TH to be of greater efficacy than the pMDI at the same nominal dose [8][9][10][11][12][13].Two studies were...

The Protective Effect of Salbutamol Inhaled Using Different Devices on Methacholine Bronchoconstriction

“…A previous, well-designed comparative study 10 demonstrated that salbutamol, 200 g, given via Turbuhaler showed a significantly better response than when given via pMDI, but no difference was observed among salbutamol, 50 g and 100 g, via Turbuhaler and salbutamol, 200 g, via pMDI. In another study, 12 it was demonstrated that half the dose given via Turbuhaler will produce the same effect as the full dose given via pMDI. However, these studies evaluated the bronchodilation effect of salbutamol administered at two different dose levels.…”

“…[7][8][9] However, Lofdahl et al 10 demonstrated that salbutamol, 200 g, given via the Turbuhaler (AstraZeneca; Lund, Swenden) induced a significantly better response than when given via pMDI, and studies have shown that the Turbuhaler delivers about twice as much the amount of drug to the lungs as the pMDI. 11,12 A method often used in the evaluation of the efficacy of inhaled drugs is the protective effect on methacholine or histamine-induced bronchoconstriction. 13,14 The inhalation of a short-acting ␤ 2agonist increases the provocative dose of inhaled methacholine or histamine from 1.1 to 3.9 doubling doses.…”