Pharmacokinetic differences between chlorofluorocarbon and chlorofluorocarbon-free metered dose inhalers of beclomethasone dipropionate in adult asthmatics

We have compared the serum pharmacokinetics of the metabolites of beclometh asone dipropionate after inhalation from chlorofluorocarbon (CFC) and hydro fluoroalkane HFA-134a (HFA) formulations in asthmatic patients. Twenty-three patients completed this open-label, randomized, single-dose, t hree-period crossover study. Each patient received in separate periods 200 mu g or 400 mu g HFA-beclomethasone dipropionate, or 400 mu g CFC-beclometh asone dipropionate. Venous blood samples were collected over 24 h for the d etermination of beclomethasone esters and beclomethasone in the serum. Significant differences in pharmacokinetics following HFA- and CFC-beclomet hasone dipropionate were observed. Following a 400 mu g beclomethasone dipr opionate dose, the HFA formulation gave mean maximum concentrations (C-max) and area under the curve (AUC) values of beclomethasone esters of 1153 pg mL(-1) and 4328 pg h mL(-1), respectively, and beclomethasone C-max and AUC values of 69 pg mL(-1) and 682 pg h mL(-1) respectively. These values were approximately 2-3-fold those seen with the CFC formulation (beclomethasone eaters C-max and AUC of 380 pg mL(-1) and 1764 pg h mL(-1), respectively; beclomethasone C-max and AUC of 41 pg mL(-1) and 366 pg h mL(-1) respective ly). Beclomethasone esters, the major component of beclomethasone dipropion ate in the serum, peaked significantly earlier for the HFA formulation (0 . 8 h) than for the CFC formulation (2 h). Tests for dose proportionality of beclomethasone esters pharmacokinetics following HFA-beclomethasone diprop ionate showed that the two hydrofluoroalkane strengths were proportional. The more rapid and greater efficiency of systemic drug delivery of the HFA formulation compared with the CFC formulation can be explained if most of e ach inhalation from CFC-beclomethasone dipropionate is swallowed and absorb ed orally, whereas most of each inhalation from HFA-beclomethasone dipropio nate is absorbed through the lungs. There is a need for comprehensive dose- response efficacy trials, with the use of the steep portion of the dose-res ponse relationship, to evaluate the significance of these pharmacokinetic d ifferences.