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At least 19 recordsLinked to original sources
PubMed1996

Lung bioavailability of chlorofluorocarbon free, dry powder and chlorofluorocarbon containing formulations of salbutamol.

With the future advent of a world wide ban on chlorofluorocarbon containing aerosols, a study was designed to compare the in vivo lung bioavailability of salbutamol via chlorofluorocarbon-containing metered-dose inhaler (CFC), chlorofluorocarbon-free metered-dose inhaler (CFC-free), and dry powder inhaler (DPI). Twelve healthy male subjects were given 1200 micrograms salbutamol and measurements made of plasma and urinary salbutamol. CFC-free produced significantly higher plasma salbutamol levels (ng ml-1; mean and 95% CI for difference) than either CFC or DPI: Cmax, CFC-free 4.18 vs CFC 3.29 (95% CI 0.10-1.68), vs DPI 3.42 (95% CI -0.03-1.56). The ratio for the difference in Cmax between CFC and CFC-free formulations was 1.32 (95% CI 1.02-1.61). There were no significant differences between CFC and DPI formulations. Urinary salbutamol results did not reveal any significant differences between the three inhalers (micrograms 30 min-1): CFC-free 42.4, CFC 43.8, DPI 45.3. Thus, the lung bioavailability of CFC-free was greater than that of CFC or DPI formulations of salbutamol.

Adult↗
PubMed1995

Clinical equivalence of a novel non-chlorofluorocarbon-containing salbutamol sulfate metered-dose inhaler and a conventional chlorofluorocarbon inhaler in patients with asthma.

BACKGROUND: New formulations of non-chlorofluorocarbon-containing propellants for pressurized metered-dose inhaler delivery systems must be developed in response to the forthcoming ban on chlorofluorocarbon (CFC) production. OBJECTIVE: This study compared the bronchodilator effects of 100, 200, and 300 micrograms (base equivalent) of salbutamol in a novel CFC-free propellant system (Airomir in the 3M CFC-Free System; 3M Pharmaceuticals, St. Paul, Minn.; 108 micrograms of salbutamol sulfate or 90 micrograms of salbutamol base equivalent per inhalation) with that of 100 and 200 micrograms of salbutamol base in a conventional CFC propellant system (Ventolin, CFC-11/12; Allen and Hanburys, Division of Glaxo Inc., Research Triangle Park, N.C.; 90 micrograms of salbutamol base per inhalation) and placebo. METHODS: Twenty-six patients with chronic, stable asthma, who had a forced expiratory volume in 1 second (FEV1) between 50.0% and 75.0% of predicted normal value, entered this randomized, double-blind, double-dummy, 6-period, crossover study. FEV1 was measured before and at multiple time points (ranging from 10 to 480 minutes) after administration of one, two, and three inhalations of salbutamol/CFC-free (100, 200, and 300 micrograms); one and two inhalations of salbutamol/CFC (100 and 200 micrograms); and placebo. Safety parameters included adverse events, heart rate, blood pressure, physical examinations, electrocardiograms, and clinical laboratory tests. Parametric analysis of variance models appropriate for a 6-period crossover design were used, along with multiple comparisons according to Tukey's method. RESULTS: All active treatments produced significantly (p < 0.0001) greater bronchodilation than placebo. The bronchodilator effect, as measured by FEV1 (peak percent change, peak as a percent of predicted value, duration, and area under the curve) after two inhalations of salbutamol/CFC-free was clinically comprable to two inhalations of salbutamol/CFC, with no clinically meaningful differences in safety parameters between the two delivery systems or between different dose levels. CONCLUSION: These results suggest that salbutamol/CFC-free may offer a suitable alternative for salbutamol/CFC when the need arises to change from CFC-containing salbutamol products.

Administration, Inhalation↗
PubMed1998

Evaluation of a non-chlorofluorocarbon formulation of cromolyn sodium (Intal) metered-dose inhaler versus the chlorofluorocarbon formulation in the treatment of adult patients with asthma: a controlled trial.

BACKGROUND: Cromolyn sodium is a nonsteroidal inhaled antiinflammatory agent for the treatment of asthma. As with other pressurized aerosol medications, the metered-dose inhaler (MDI) formulation currently contains chlorofluorocarbon (CFC) propellants. Because of their harmful effects on the environment CFCs are now generally banned from production and use. Alternative propellants under production for MDIs include derivatives of hydrofluoroalkane (HFA). This study uses HFA-227 in an MDI formulation of cromolyn sodium. OBJECTIVES: The objectives of the study were (1) to examine the efficacy and safety of an HFA formulation of cromolyn sodium (Intal) MDI and (2) to compare the HFA formulation with the CFC formulation. METHODS: A multicenter, randomized, double-blind, placebo-controlled, parallel study with two active groups (HFA-cromolyn sodium [n = 113] and CFC-cromolyn sodium [n = 107]) and a placebo-treated group (n = 105). RESULTS: Patients treated with either formulation of cromolyn sodium MDI showed a statistically significant (p < 0.05) improvement of 12% to 18% compared with placebo in symptom summary score, daytime asthma symptoms, and albuterol use. No statistically significant differences were observed in pulmonary function. Patient and physician opinions of overall effectiveness favored HFA-cromolyn sodium over placebo (p = 0.01), with no other significant between-treatment differences. No statistically significant differences existed among groups in the incidence of treatment-related adverse events. CONCLUSION: The HFA formulation of cromolyn sodium MDI is a well- tolerated and active alternative treatment for asthma patients aged 12 years and more.

Administration, Inhalation↗
PubMed1998

Postmarketing surveillance study of a non-chlorofluorocarbon inhaler according to the safety assessment of marketed medicines guidelines.

OBJECTIVE: To evaluate the safety of a non-chlorofluorocarbon metered dose salbutamol inhaler. DESIGN: This was a postmarketing surveillance study, conducted under formal guidelines for company sponsored safety assessment of marketed medicines (SAMM). A non-randomised, non-interventional, observational design compared patients prescribed metered doses of salbutamol delivered by inhalers using either hydrofluoroalkane or chlorofluorocarbon as the propellant. Follow up was three months. SETTING: 646 general practices throughout the United Kingdom. SUBJECTS: 6614 patients with obstructive airways disease (1667 patient years of exposure). MAIN OUTCOME MEASURES: Proportions of patients who were: admitted to hospital for respiratory diseases, reported adverse side effects, or withdrew because of adverse affects. RESULTS: There were no significant differences between the hydrofluoroalkane (HFA 134a) and chlorofluorocarbon inhaler groups in relation to the proportions of patients admitted to hospital for respiratory diseases (odds ratio 0.75; 95% confidence interval 0.51 to 1.08) or the proportions who reported adverse events (1.01; 0.88 to 1.17). However, more patients using the hydrofluoroalkane inhaler than the chlorofluorocarbon inhaler withdrew because of adverse events (3.8% and 0.9% respectively). CONCLUSION: The hydrofluoroalkane inhaler was as safe as the chlorofluorocarbon inhaler when judged by hospital admissions and adverse affects. The study design successfully fulfilled the recommendations of the guidelines. Differences between postmarketing surveillance studies and randomised clinical trials in assessing safety were identified. These may lead to difficulties in the design of postmarketing surveillance studies.

Adult↗
PubMedDate not supplied

[Chlorofluorocarbons--a new environmental health problem].

A review of health problems caused by the use of chlorofluorocarbons--chemical substances of widespread and varied applications is presented. There is a recent evidence that fully halogenated chlorofluorocarbons are air pollutants inducing hazardous health effects. Direct effects of chlorofluorocarbons on respiratory and cardiac functions are described among which some with lethal outcome. Recent data are given and models described forecasting indirect effects of chlorofluorocarbons induced by their ozone depleting reactions in the stratosphere which bring about a higher exposure of the population to UV-B radiation. As a consequence of which, an increase of the incidence of nonmelanoma and melanoma skin cancers, immunosuppression, and eye disorders is predicted. The latest international activities aimed at urgent prevention of these effects are described.

Air Pollutants↗
PubMedDate not supplied

Metabolism of the chlorofluorocarbon substitute 1,1-dichloro-2,2,2-trifluoroethane by rat and human liver microsomes: the role of cytochrome P450 2E1.

1,1-Dichloro-2,2,2-trifluoroethane (HCFC-123) has been developed as a substitute for ozone-depleting chlorofluorocarbons. The atmospheric lifetime of HCFC-123 is expected to be much shorter than those of chlorofluorocarbons; however, due to its lower stability and the presence of carbon-hydrogen bonds, metabolism of HCFC-123 in mammals and metabolism-dependent toxicity is likely. We compared the metabolism of HCFC-123 and its analog halothane in rat and human liver microsomes. 19F-NMR studies showed that trifluoroacetic acid is a major metabolite of HCFC-123. Besides trifluoroacetic acid, chlorodifluoroacetic acid and inorganic fluoride were identified as products of the enzymatic oxidation of HCFC-123 in rat and human liver microsomes by 19F-NMR and mass spectrometry. The metabolites were not detected in incubations with halothane. HCFC-123 and halothane were transformed by liver microsomes from untreated rats at low rates. Microsomes from ethanol-and pyridine-treated rats metabolized both HCFC-123 and halothane at much higher rates. These microsomes also exhibited high rates of p-nitrophenol oxidation. p-Nitrophenol is a model substrate mainly oxidized by P450 2E1 to p-nitrocatechol. Samples of human liver microsomes showed considerable differences in the extent of HCFC-123, p-nitrophenol oxidation, and chlorzoxazone hydroxylation. In human liver microsomes, rabbit anti-rat P450 2E1 IgG recognized a single protein band corresponding in apparent molecular weight to human P450 2E1. Immunoblot analysis revealed considerable heterogenity in the P450 2E1 protein content of the human liver samples. Trifluoroacetic acid formation from HCFC-123 and halothane and p-nitrocatechol formation from p-nitrophenol were significantly reduced by the P450 2E1 inhibitor diethyldithiocarbamate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Toxicology of chlorofluorocarbon replacements.

Chlorofluorocarbons (CFCs) are stable in the atmosphere and may reach the stratosphere. They are cleaved by UV-radiation in the stratosphere to yield chlorine radicals, which are thought to interfere with the catalytic cycle of ozone formation and destruction and deplete stratospheric ozone concentrations. Due to potential adverse health effects of ozone depletion, chlorofluorocarbon replacements with much lower or absent ozone depleting potential are developed. The toxicology of these compounds that represent chlorofluorohydrocarbons (HCFCs) or fluorohydrocarbons (HFCs) has been intensively studied. All compounds investigated (1, 1-dichloro-1-fluoroethane [HCFC-141b], 1,1,1,2-tetrafluoroethane [HFC-134a], pentafluoroethane [HFC-125], 1-chloro- 1,2,2,2-tetrafluoroethane [HCFC-124], and 1,1-dichloro-2,2,2-trifluoroethane [HCFC-123]) show only a low potential for skin and eye irritation. Chronic adverse effects on the liver (HCFC-123) and the testes (HCFC-141b and HCFC-134a), including tumor formation, were observed in long-term inhalation studies in rodents using very high concentrations of these CFC replacements. All CFC replacements are, to varying extents, biotransformed in the organism, mainly by cytochrome P450-catalyzed oxidation of C-H bonds. The formed acyl halides are hydrolyzed to give excretable carboxylic acids; halogenated aldehydes that are formed may be further oxidized to halogenated carboxylic acids or reduced to halogenated alcohols, which are excretory metabolites in urine from rodents exposed experimentally to CFC replacements. The chronic toxicity of the CFC replacements studied is unlikely to be of relevance for humans exposed during production and application of CFC replacements.

Animals↗
PubMed1991

Chlorofluorocarbon interaction with DPPC vesicles: an ESR investigation.

The effect of the chlorofluorocarbon halotane on DPPC unilamellar vesicles was investigated by Electron Spin Resonance (ESR) spectroscopy. The X-band ESR spectra showed prominent thermotropic behaviour of the interfacial region of vesicles at different halotane concentrations. A model of molecular interaction between phospholipids and chlorofluorocarbon is also proposed.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1995

Colonic spreading of a non-chlorofluorocarbon mesalazine rectal foam enema in patients with quiescent ulcerative colitis.

BACKGROUND: Rectal foam enemas provide for drug delivery to the distal colon for treatment of left sided ulcerative colitis. However, currently available formulations contain chlorofluorocarbons which are due to be phased out in the near future. The objective of this study was therefore to determine the degree of dispersion of a newly developed non-chlorofluorocarbon rectal foam preparation in ulcerative colitis patients. METHODS: This was an open label non-controlled study of a single administration of a mesalazine foam enema (two actuations containing 2 g of mesalazine in approximately 120 mL foam) in 10 patients with quiescent ulcerative colitis. Spreading of the 99mTc-labelled foam enema was assessed over a 4-h period by the non-invasive technique of gamma scintigraphy. RESULTS: All patients retained the enema for the full 4-h imaging period. In nine out of the 10 patients, the enema was observed to spread as far as the descending colon and on average 23% of the dose was present in the descending colon at 4 h post-dose. CONCLUSIONS: The extent of spreading observed in the study supports the use of the formulation in the treatment of left sided ulcerative colitis.

Aminosalicylic Acids↗
PubMed1997

Epidemic of liver disease caused by hydrochlorofluorocarbons used as ozone-sparing substitutes of chlorofluorocarbons.

BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.

Biomarkers↗
PubMedDate not supplied

Pentahaloethane-based chlorofluorocarbon substitutes and halothane: correlation of in vivo hepatic protein trifluoroacetylation and urinary trifluoroacetic acid excretion with calculated enthalpies of activation.

The hydrochlorofluorocarbons (HCFCs) 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) and 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124) and the hydrofluorocarbon (HFC) pentafluoroethane (HFC-125) are being developed as substitutes for chlorofluorocarbons that deplete stratospheric ozone. The structural similarity of these HCFCs and HFCs to halothane, which is hepatotoxic under certain circumstances, indicates that the metabolism and cellular interactions of HCFCs and HFCs must be explored. In a previous study [Harris et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 1407], similar patterns of trifluoroacetylated proteins (TFA-proteins) were detected by immunoblotting with anti-TFA-protein antibodies in livers of rats exposed to halothane or HCFC-123. The present study extends these results and demonstrates that in vivo TFA-protein formation resulting from a 6-h exposure to a 1% atmosphere of these compounds follows the trend: halothane approximately HCFC-123 much greater than HFC-124, greater than HFC-125. The calculated enthalpies of activation of halothane, HCFC-123, HCFC-124, and HFC-125 paralleled the observed rate of trifluoroacetic acid excretion in HCFC- or HFC-exposed rats. Exposure of rats to a range of HCFC-123 concentrations indicated that TFA-protein formation was saturated at an exposure concentration between 0.01% and 0.1% HCFC-123. Deuteration of HCFC-123 decreased TFA-protein formation in vivo. Urinary trifluoroacetic acid excretion by treated rats correlated with the levels of TFA-proteins found after each of these treatments. No TFA-proteins were detected in hepatic fractions from rats given 1,1,1,2-tetrafluoroethane (HFC-134a), which is not metabolized to a trifluoroacetyl halide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Tissue acylation by the chlorofluorocarbon substitute 2,2-dichloro-1,1,1-trifluoroethane.

Hydrochlorofluorocarbons (HCFCs) are being developed as substitutes for ozone-depleting chlorofluorocarbons (CFCs); because widespread human exposure to HCFCs may be expected, it is important to evaluate their toxicities thoroughly. Here we report studies on the bioactivation of the CFC substitute 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) to an electrophilic intermediate that reacts covalently with liver proteins. HCFC-123 and its analog halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) were studied in rats by 19F NMR spectroscopy, and we found that a trifluoroacetylated lysine adduct was formed with liver proteins. Also, the pattern of proteins immunoreactive with hapten-specific anti-trifluoroacetylprotein antibodies was identical in livers of HCFC-123- and halothane-exposed rats. Because halothane causes an idiosyncratic, and sometimes fatal, hepatitis that is associated with an immune response against several trifluoroacetylated liver proteins, the present findings raise the possibility that humans exposed to HCFC-123 or structurally related HCFCs may be at risk of developing an immunologically mediated hepatitis.

Acylation↗
PubMed1992

The kidney as a novel target tissue for protein adduct formation associated with metabolism of halothane and the candidate chlorofluorocarbon replacement 2,2-dichloro-1,1,1-trifluoroethane.

Hydrochlorofluorocarbons (HCFCs) have been identified as chemical replacements of the widely used chlorofluorocarbons (CFCs) that are implicated in stratospheric ozone depletion. Many HCFCs are structural analogues of the anesthetic agent halothane and may follow a common pathway of biotransformation and formation of adducts to protein-centered and other cellular nucleophiles. Exposure of rats to a single dose of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) or of the candidate CFC substitute HCFC 123 (2,2-dichloro-1,1,1-trifluoroethane) led to the formation of trifluoroacetylated protein adducts (CF3CO-proteins) not only in the liver, but also in the kidney as a novel target tissue for protein trifluoroacetylation. CF3CO-proteins in the kidney amounted to about 5% of those formed in the liver of the same animal. The amount of CF3CO-proteins formed within the kidney was roughly reflected by the capacity of metabolism of halothane or HCFC 123 by rat kidney microsomes in vitro which amounted to about 10% of that observed with liver microsomes. By immunohistochemistry, CF3CO-proteins in the kidney were mainly localized in the tubular segments of the cortex. In the liver, the density of CF3CO-proteins decreased from the central vein towards the portal triad. In vitro incubation of rat liver microsomes with halothane or HCFC 123 resulted in extensive formation of CF3CO-proteins and reproduced faithfully the pattern of liver CF3CO-proteins obtained in vivo. CF3CO-proteins generated in vitro were immunochemically not discernible from those generated in vivo. Glutathione (5 mM) and cysteine (5 mM) virtually abolished CF3CO-protein formation; the release of Br- from halothane and Cl- from HCFC 123 was reduced to much lesser a degree. S-Methyl-glutathione, N-acetyl-cysteine, methionine, and N-acetyl-methionine only slightly affected the formation of CF3CO-proteins or metabolism of either substrate. The data suggest that metabolism and concomitant CF3CO-protein formation of halothane or of candidate CFC replacements like HCFC 123 is not restricted to the liver but also takes place in the kidney. Furthermore, an in vitro system for CF3CO-protein formation has been developed and used to show that protein-centered and glutathione-centered nucleophilic sites compete for intermediates of metabolism of halothane or of HCFC 123.

Animals↗
PubMed1999

Switching patients with asthma from chlorofluorocarbon (CFC) albuterol to hydrofluoroalkane-134a (HFA) albuterol.

Chlorofluorocarbon (CFC) propellants deplete stratospheric ozone. Production and use of CFCs, except for certain critical exemptions, has been prohibited by the Montreal Protocol. Use of CFCs as propellants in metered-dose inhalers (MDIs) is still allowed, but the U.S. Food and Drug Administration is planning the transition to alternative propellants for use in MDIs. Hydrofluoroalkane-134a (HFA), a non-ozone-depleting propellant, has been used to reformulate albuterol (HFA albuterol). This study evaluates whether comparable safety and efficacy continues for 12 weeks after patients with asthma are switched from CFC albuterol to HFA albuterol. Patients with asthma stabilized on CFC albuterol during a 12-week safety and efficacy trial were randomized to either continue receiving CFC albuterol or to be switched to receive HFA albuterol in a yearlong safety and efficacy trial. Safety and efficacy were compared over the first 12 weeks of the yearlong trial between patients who had remained on CFC albuterol and those who had been switched to HFA albuterol. Bronchodilator efficacy was evaluated by serial spirometry for 6 hr after the patients self-administered the study drug in the clinic. Safety was assessed by measuring changes in pulse rate, blood pressure, and electrocardiogram (ECG) intervals after dosing with study drug, monitoring adverse events, and performing prestudy and poststudy laboratory testing and physical examinations. No significant differences in bronchodilator efficacy between the patients continuing to receive CFC albuterol and those switched to HFA albuterol were found in the 12 weeks after the switch. No differences between the two products were found for changes in pulse rate, blood pressure, and ECG intervals. Adverse event profiles were similar for the two products, except the patients remaining on CFC albuterol reported increased asthma symptoms and rhinitis significantly more often than the patients switched to HFA albuterol. No clinically meaningful changes in laboratory tests or physical examinations were found in either treatment group. Patients with asthma switched from CFC albuterol to HFA albuterol receive comparable bronchodilation with a similar safety profile as those continuing to receive CFC albuterol.

Adult↗
PubMed1993

Interaction of fluoroethane chlorofluorocarbon (CFC) substitutes with microsomal cytochrome P450. Stimulation of P450 activity and chlorodifluoroethene metabolism.

The abilities of halothane and the fluoroethane chlorofluorocarbon (CFC) substitutes, FC-123, FC-133a, FC-124, FC-134a and FC-125, to stimulate cytochrome P450 activities and 2-chloro-1,1-difluoroethene (CDE) defluorination in hepatic microsomes from phenobarbital-treated rabbits were compared. At 1% (v/v) each, halothane and FC-123 similarly increased the consumption of NADPH and O2 by 300 and 100%, respectively, over that in microsomes without substrate. FC-133a and FC-124 were less effective, increasing NADPH and O2 consumption by 150-200 and 70%. FC-134a and FC-125 were the least effective, increasing NADPH and O2 consumption by only 70 and 50%, respectively. No metabolism of any fluoroethane could be detected under the incubation conditions used. Halothane and FC-123 were most effective in stimulating CDE metabolism with increases of CDE defluorination ranging from 1.5- to 2-fold. FC-133a and FC-124 enhanced CDE oxidation 89 and 74%, respectively, and FC-134a and FC-125 had no effect. While CDE metabolism was enhanced in the presence of the fluoroethanes, no additional NADPH or O2 was consumed when halothane or FC-124 was incubated with CDE compared with incubations containing only halothane or FC-124. Log-log plots of NADPH consumption and CDE metabolism with the olive oil/gas partition coefficients of each fluoroethane showed linear relationships. These data demonstrate that the activity of the fluoroethanes in stimulating P450 activity and CDE metabolism is a function of their lipid solubility, and fluoroethane-enhanced CDE metabolism is related to the ability of these compounds to increase uncoupled P450 activity.

Animals↗
PubMed1994

Mass spectral study of chlorofluorocarbons (CFCs) and potential alternatives (HCFCs and HFCs).

Owing to high ozone depletion potential of the chlorofluorocarbons (CFCs), the production of such substances has been regulated worldwide by the Montreal Protocol in 1987. There is an urgent need to find other suitable products to replace them and hydrochlorofluorocarbons (HCFCs) and hydrofluorocarbons (HFCs) are considered to be the most probable candidates as CFC alternatives. The HCFCs and HFCs are more susceptible to decomposition during use than CFCs because they contain hydrogen. Toxicological data on these alternative fluorocarbons are being developed. A systematic investigation of these compounds has been undertaken to establish the fragmentation patterns. Electron impact mass spectra are reported for HCFCs and HFCs. Fragmentation mechanisms are presented and discussed on the basis of variable energy (11 to 30 eV) spectra. At low ionization energy, it is possible to describe an order of fragmentation for each compound. This may lead to the possibility of classifying them according to characteristic behaviors.

Chlorofluorocarbons↗
PubMed1998

Hydrofluoroalkane-134a beclomethasone dipropionate extrafine aerosol provides equivalent asthma control to chlorofluorocarbon beclomethasone dipropionate at approximately half the total daily dose.

The mandatory requirement to eliminate chlorofluorocarbons (CFCs) as propellants in pharmaceutical aerosols has provided the opportunity to enhance significantly the delivery of aerosol drugs to the respiratory tract. This randomized, parallel-group, double-blind, double-dummy, multicentre study was undertaken to assess whether beclomethasone dipropionate (BDP) in hydrofluoroalkane-134a (HFA) provided equivalent control of moderately severe asthma to BDP in CFC but at approximately half the total daily dose, as might be expected from the improved lung deposition of the HFA-BDP extrafine aerosol. The novel study design included a 10-12 day run-in period to confirm that patients met established criteria of moderately severe asthma and were symptomatic on current therapy (inhaled beta-agonist plus CFC-BDP 400-800 micrograms day-1). This run-in period was followed by a short course of oral steroid therapy (prednisolone 30 mg day-1 for 7-13 days) to demonstrate steroid responsiveness [> or = 15% improvement in morning peak expiratory flow (PEF)] and to provide a within-study baseline of improved asthma control. A total of 233 patients were randomized to treatment for 12 weeks with HFA-BDP 800 micrograms day-1 (116 patients) or CFC-BDP 1500 micrograms day-1 (117 patients). The mean change from oral steroid treatment in morning PEF with HFA-BDP was equivalent to that seen with CFC-BDP at all time intervals. Changes in other measures of pulmonary function, asthma symptom scores and beta-agonist use were equivalent in the two treatment groups throughout the 12 week treatment period. The safety profile of HFA-BDP compared favourably with that of CFC-BDP with no unexpected adverse events reported. Fewer patients on HFA-BDP than on CFC-BDP had plasma cortisol levels below the normal reference range after 12 weeks of therapy (5.1% vs. 17.3%, respectively). In conclusion, HFA-BDP extrafine aerosol was found to provide equivalent control of moderately severe asthma to CFC-BDP at approximately half the daily dose with a favourable safety profile, suggesting an improved therapeutic ratio.

Administration, Inhalation↗