Bioavailability of Beclometasone From Two HFA-BDP Formulations With a Spacer.

BACKGROUND: The drug delivery characteristics of each inhaler/spacer combination are unique. The spacer size as well as the presence of electrostatic charge greatly influence the inhaler dose emission and in vivo delivery. Using a previously developed urinary pharmacokinetic method, we have measured the relative lung and systemic bioavailability of beclometasone dipropionate (BDP) after inhalation from 2 hydrofluroalkane-beclometasone dipropionate (HFA-BDP) formulations when used with a spacer. METHODS: 12 healthy volunteers received 8 randomized doses, separated by 7 d, of inhaled of BDP with either the Clenil pressurized metered-dose inhaler (pMDI; 250 µg) or the breath-actuated Qvar Easi-Breathe inhaler (100 µg), used alone or with a spacer. The urinary amounts of BDP excreted and retained in the spacer were assayed using a liquid chromatographic mass spectrometer. The spacer was assessed after washing with a detergent solution that was either rinsed or not rinsed with water. In addition, the aerodynamic characterization of each inhaler/spacer combination was assessed using the Andersen Cascade Impactor operated at 28 L/min using a 4-L inhalation volume. The amount of BDP deposited in the induction port, spacer, and various Anderson Cascade Impactor stages were determined. RESULTS: The in vivo 30-min urinary excretion and the in vitro fine particle dose results were only slightly affected by adding the spacer to the Clenil pMDI or the Qvar Easi-Breathe inhaler. However, the spacer significantly reduced drug particle impaction in the oropharynx and minimized deposition in the gastrointestinal tract. Therefore, using spacers with BDP inhalers is associated with a more favorable therapeutic ratio because it has little effect on lung dose, but it significantly reduced throat deposition. An improved lung deposition was achieved with non-rinsed spacers compared to spacers rinsed with water. CONCLUSION: The difference in the BDP particle size between formulations as well as spacer size greatly affected drug deposition in different regions of the respiratory tract.

Detection of synthetic glucocorticoids by liquid chromatography-tandem mass spectrometry in patients being investigated for Cushing's syndrome.

BACKGROUND: We report a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the detection of four commonly prescribed steroid drugs (prednisolone, dexamethasone, betamethasone and beclomethasone dipropionate) while simultaneously measuring 24-h urine free cortisol and cortisone in patients. METHODS: Two hundred and fifty microlitre aliquots of urine were spiked with internal standard and extracted with dichloromethane. The MS instrument was operated with positive electrospray and multiple reaction monitoring. Two transitions were monitored for each analyte of interest and the ratio of the intensities of the product ion fragments was established. RESULTS: The LC-MS/MS method for the measurement of urine free cortisol and cortisone was established. The assay was linear up to 788 nmol/L for cortisol and 777 nmol/L for cortisone, with a limit of quantitation of 5.0 nmol/L for both. Analysis time per sample was seven minutes. Transitions for four synthetic glucocorticoids were included, and they were identified based on the ratio of the intensities of product ion fragments. Analysis of 219 samples collected from 154 patients (55 male and 99 female) revealed the presence of prednisolone in five samples from three patients. Dexamethasone was detected in samples from four patients, and betamethasone was detected in one sample. CONCLUSION: This is the first LC-MS/MS method in routine use to combine quantification of urinary cortisol and cortisone and detection of synthetic glucocorticoids in patients being investigated for Cushing's syndrome. Since the most common quoted cause of Cushing's syndrome is steroid treatment, this is a valuable diagnostic tool.

Simultaneous determination of beclomethasone, beclomethasone monopropionate and beclomethasone dipropionate in biological fluids using a particle beam interface for combining liquid chromatography with negative-ion chemical ionization mass spectrometry.

A new simple and sensitive assay has been developed for the simultaneous quantitative measurement of beclomethasone dipropionate and its hydrolysis products in human plasma and urine. Beclomethasone 17.21-dipropionate, beclomethasone 17-monopropionate, beclomethasone and the internal standard, dexamethasone 21-acetate, were measured by combined liquid chromatography and negative-ion chemical ionization mass spectrometry with methane as the reagent gas. A particle beam interface from Hewlett Packard was used. Under mild operating conditions, abundant and stable characteristic high-mass ions were generated in the ion source of the mass spectrometer by a resonance electron-capture mechanism. The fast extraction procedure requires 1 ml of plasma or urine, and the quantification limit of the method is 1 ng ml-1 for the three tested compounds.

Comparison of beclomethasone dipropionate and prednisolone 21-phosphate enemas in the treatment of ulcerative proctitis.

In a double-blind randomized clinical trial 18 patients with exacerbations of distal ulcerative colitis were treated for 4 weeks with enemas containing either prednisolone 21-phosphate 30 mg (PP) or beclomethasone dipropionate 1 mg (BDP) a surface-active corticosteroid. All 8 patients treated with PP showed clinical and endoscopic improvement in contrast with only 4 of 10 patients treated with BDP. Endocrinologic evaluation showed a significant decrease in morning plasma cortisol, in cortisol increase after synacthen, and in urinary free cortisol excretion after PP therapy, but no changes in these variables after BDP therapy. We conclude that PP enemas are more active in the treatment of ulcerative proctitis, but they cause a suppression of the adrenal cortex, in contrast to BDP.

Beclomethasone dipropionate aerosol in treatment of hay fever in children.

Eighteen children suffering from hay fever were treated with intra-nasal beclomethasone dipropionate (400 mug/day) and an identical placebo aerosol in a double-blind cross-over trial. 17 of the children preferred the intranasal beclomethasone dipropionate, one had no preference, none preferred the placebo. The effect on the nasal symptoms was impressive. Symptom scores decreased, on average, to 12% and the number of antihistamine tablets taken to 18% of the pretreatment amount. Some beneficial effect on eye symptoms was also discernible, possibly due to an indirect influence from the nasal mucosa via the nasolacrimal reflex. Adrenal function was not affected. It was concluded that 400 mug beclomethasone dipropionate given intranasally daily for some weeks is an effective and safe treatment for hay fever in children.