Equivalence of as-required salbutamol propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics. German Study Group.

This randomized, double-blind, parallel-group study compared the efficacy and tolerability of as-required salbutamol 100 microg administered from either a chlorofluorocarbon (CFC) pressurized metered dose inhaler (pMDI; Ventolin) or from a non-CFC hydrofluoroalkane (HFA) 134a pMDI (Ventolin CFC-free) in patients with mild to moderate asthma. All patients (n = 423) continued with their standard asthma therapy, and recorded their daily use of study medication, morning and evening peak expiratory flow (PEF) and symptom scores, throughout the 4-week treatment period. Clinic lung function was measured at 2-week intervals. The median daily use of inhaled study medication remained constant at four actuations per day throughout the study in both treatment groups and statistical analysis indicated that the two formulations were equivalent. Small improvements in both treatment groups were reported in mean morning and evening PEF, clinic forced expiratory volume in 1 sec and clinic PEF and there were no significant differences between the two groups. Both formulations were well tolerated. This study indicates that as-required salbutamol 100 microg administered via a HFA 134a pMDI is as effective and safe as the currently available CFC-propelled formulation.

The salmeterol/fluticasone combination is more effective than fluticasone plus oral montelukast in asthma.

The aim of this study was to compare the efficacy and safety of salmeterol/fluticasone propionate combination product (SFC) with fluticasone propionate (FP) plus oral montelukast (M) over 12 weeks in symptomatic asthma patients. The study was a multinational, randomised, double-blind, double-dummy, parallel-group design in patients aged > or = 15 years. After a 4-week run-in during which all patients received FP 100 microg twice daily, patients were randomised to inhaled SFC (50/100 microg) twice daily or inhaled FP 100 microg twice daily and oral M 10 mg once daily. Patients kept daily records of their peak expiratory flow (PEF) symptom scores and use of rescue medication. Over the 12-week treatment period, the adjusted increase in mean morning PEF was significantly greater in the SFC group (36 l/min) than the FP/M group (19 l/min; P < 0.001). The improvement in FEV1 was also significantly greater in the SFC group (mean treatment difference 0.11 l; P < 0.001). SFC provided significantly better control of daytime and night-time symptoms and there were fewer exacerbations. Patients in the SFC group were also significantly more likely to have a rescue-free day. Both treatments were equally well tolerated. Combination therapy with FP plus salmeterol (SFC) produced significantly greater improvements in lung function and asthma control than the addition of montelukastto FP.

Cost effectiveness of fluticasone propionate and flunisolide in the treatment of corticosteroid-naive patients with moderate asthma.

OBJECTIVE: The aim of this study was to determine the cost effectiveness of 2 inhaled corticosteroids, fluticasone propionate and flunisolide, in the management of asthma from a third-party payer perspective in Germany (German Sickness Fund). DESIGN AND SETTING: Direct treatment costs were retrospectively applied to 2 prospective randomised parallel group clinical trials conducted in Germany comparing fluticasone propionate and flunisolide: one 6-week open-label study (n = 332) and one 8-week double-blind study (n = 308) in corticosteroid-naive patients with asthma of moderate severity aged between 18 and 70 years. All costs were adjusted to 1997 Deutschmarks. Efficacy parameters included changes in morning and evening peak expiratory flow rate (PEFR) measurements, the number of successfully treated patients (defined as those with a PEFR improvement of > or = 10%) and proportion of symptom-free days. MAIN OUTCOME MEASURES AND RESULTS: The fluticasone propionate groups had higher respective proportions of successfully treated patients and symptom-free days than the flunisolide groups in both the open-label (56.8 vs 39.6% and 36.4 vs 28.5%) and double-blind (55.3 vs 44.5% and 35.1 vs 31.1%) studies. Improvements in both morning and evening PEFR measurements were also significantly (p < 0.01) greater with fluticasone propionate than with flunisolide. Although average daily treatment costs were slightly higher in the fluticasone propionate groups than in the flunisolide groups, all cost-effectiveness ratios (daily cost per successfully treated patient and daily cost per symptom-free day) favoured fluticasone propionate. Sensitivity analysis showed that these results were robust over a wide range of assumptions. CONCLUSION: In these patients, management with fluticasone propionate was more cost effective than with flunisolide in the German healthcare setting.

Competition between oxalate and phosphate during active calcium accumulation by sarcoplasmic vesicles.

1. During ATP supported active calcium uptake oxalate as well as phosphate are accumulated with calcium. The uptake of calcium exceeds that of both anions by a small quantity--accounting for calcium binding to vesicular proteins and lipids. 2. From assay media containing phosphate and oxalate--nearly exclusively either oxalate or phosphate are taken up together with calcium by the sarcoplasmic reticulum vesicles. The mutual exclusion occurs in a very narrow concentration range of the anions. 3. In solutions containing phosphate and oxalate, calcium phosphate or calcium oxalate precipitates are formed according to their solubility properties. 4. When phosphate prevents oxalate from being taken up, calcium transport is inhibited. Inhibition occurs, because the concentration of ionized calcium inside the vesicles rises approximately 100-fold when oxalate is replaced by phosphate. The activity of the calcium dependent ATPase parallels the calcium uptake activity. 5. It is excluded that the inhibition of calcium uptake produced by phosphate is caused by an enhanced permeability of the sarcoplasmic reticulum membranes for calcium in the presence of phosphate.