[COMPARATIVE STUDIES ON THE EOSINOPENIC EFFECTS OF GLUCOCORTICOIDS AFTER ORAL ADMINISTRATION AND INHALATION].
Explore the source record for details and available documents.
Administration, Inhalation↗
SEARCH · Search PubMed
Results for “Administration, Inhalation”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Acute and sustained effects of early administration of inhaled nitric oxide to children with acute respiratory distress syndrome.
OBJECTIVE: To determine the acute and sustained effects of early inhaled nitric oxide on some oxygenation indexes and ventilator settings and to compare inhaled nitric oxide administration and conventional therapy on mortality rate, length of stay in intensive care, and duration of mechanical ventilation in children with acute respiratory distress syndrome. DESIGN: Observational study. SETTING: Pediatric intensive care unit at a university-affiliated hospital. PATIENTS: Children with acute respiratory distress syndrome, aged between 1 month and 12 yrs. INTERVENTIONS: Two groups were studied: an inhaled nitric oxide group (iNOG, n = 18) composed of patients prospectively enrolled from November 2000 to November 2002, and a conventional therapy group (CTG, n = 21) consisting of historical control patients admitted from August 1998 to August 2000. MEASUREMENTS AND MAIN RESULTS: Therapy with inhaled nitric oxide was introduced as early as 1.5 hrs after acute respiratory distress syndrome diagnosis with acute improvements in Pao(2)/Fio(2) ratio (83.7%) and oxygenation index (46.7%). Study groups were of similar ages, gender, primary diagnoses, pediatric risk of mortality score, and mean airway pressure. Pao(2)/Fio(2) ratio was lower (CTG, 116.9 +/- 34.5; iNOG, 62.5 +/- 12.8, p <.0001) and oxygenation index higher (CTG, 15.2 [range, 7.2-32.2]; iNOG, 24.3 [range, 16.3-70.4], p <.0001) in the iNOG. Prolonged treatment was associated with improved oxygenation, so that Fio(2) and peak inspiratory pressure could be quickly and significantly reduced. Mortality rate for inhaled nitric oxide-patients was lower (CTG, ten of 21, 47.6%; iNOG, three of 18, 16.6%, p <.001). There was no difference in intensive care stay (CTG, 10 days [range, 2-49]; iNOG, 12 [range, 6-26], p >.05) or duration of mechanical ventilation (TCG, 9 days [range, 2-47]; iNOG, 10 [range, 4-25], p >.05). CONCLUSIONS: Early treatment with inhaled nitric oxide causes acute and sustained improvement in oxygenation, with earlier reduction of ventilator settings, which might contribute to reduce the mortality rate in children with acute respiratory distress syndrome. Length of stay in intensive care and duration of mechanical ventilation are not changed. Prospective trials of inhaled nitric oxide early in the setting of acute lung injury in children are needed.
Administration, Inhalation↗
A comparison of various types of patient instruction in the proper administration of metered inhalers.
The administration technique employed by 42 inpatients using metered inhalers were observed. Proper performance of the six steps recommended by the manufacturer provided the guidelines for correct administration. The degree of compliance with proper technique was defined as the number of steps correctly executed by the patient. The mean number of steps correctly performed was 2.9 out of the possible six (48.3 percent). Twenty-four patients were then randomized into one of three groups. Group I received the manufacturer's instruction sheet, Group 2 received counseling from a pharmacist, and Group 3 received both the manufacturer's instruction sheet and counseling from a pharmacist. There was a significant improvement in the postinstruction technique in Groups 2 and 3, while Groups 1 failed to demonstrate any significant improvement. Comparisons were then made among the three groups. No significant difference was found between Group 2 and Group 3. However, both Groups 2 and 3 were found to be significantly different (p less than 0.05) from Group 1. This study shows that pharmacist counseling can significantly improve the degree of patient compliance in the administration of metered inhalers.
Aerosols↗
Effective inhaled drug administration to mechanically ventilated patients.
Inhaled therapy is commonly employed in mechanically ventilated patients with chronic obstructive pulmonary disease or asthma. The efficacy of inhaled drugs is comparable to that achieved with systemic routes of administration, but the dose of drug required to achieve a therapeutic effect is generally much smaller. Moreover, limited systemic absorption of inhaled drugs minimises systemic side effects. Aerosol administration to ventilated patients differs from that in ambulatory patients in several respects. Optimal techniques for using pressurised metered-dose inhalers and nebulisers in ventilator circuits have been developed. With these techniques, the efficiency of inhaled drug delivery in mechanically ventilated patients is now comparable to that in ambulatory patients. Pressurised metered-dose inhalers are chiefly used to deliver bronchodilator and corticosteroid aerosols, and are more efficient and convenient to use than nebulisers for routine therapy in ventilated patients. However, nebulisers are more versatile and are employed to generate aerosols of bronchodilators, corticosteroids, antibiotics, prostaglandins, surfactant and mucolytic agents. Improvements in drug formulations and the design and efficiency of aerosol generating devices have led to increasing application of inhaled therapies in mechanically ventilated patients.
Administration, Inhalation↗
Pharmacokinetics of SDZ 64-412, a novel antiasthmatic agent, following intravenous, oral, and inhalation dosing in the rat.
The pharmacokinetics of SDZ 64-412, an antiasthmatic agent, were investigated following intravenous, oral, and inhalation dosing in rats. 14C-SDZ 64-412 was administered intravenously (2.75 mg kg-1) and orally (5.5 mg kg-1, 110 mg kg-1), whereas non-radiolabeled drug (5.04 mg kg-1) was administered using nose-only inhalation chambers. Radioactivity and parent drug concentrations in blood, lung, and excreta were determined at designated times post-dose. SDZ 64-412 was rapidly and extensively (approximately 80%) absorbed following both oral doses, although absorption appeared to be prolonged with increasing dose. The absorbed drug was shown to undergo extensive and saturable first-pass metabolism. The bioavailability of the parent drug, calculated by dose-normalized AUC and deconvolution methods, was only 10-15% from the low dose, but increased to approximately 40% following the high dose. Following inhalation dosing, SDZ 64-412 concentrations in blood and lungs increased rapidly, and did not decline immediately after termination of dosing. The inhalation dose yielded a bioavailability of approximately 40%, and AUC of the drug in lungs was approximately 25 times greater than in blood. In general, SDZ 64-412 was extensively distributed and rapidly eliminated from the systemic circulation. Biliary excretion was the predominant route of radioactivity excretion. The present findings suggest that inhalation administration provides a viable means of delivery of SDZ 64-412.
Administration, Inhalation↗
[Aerosol therapy in obstructive respiratory tract diseases: deposition, administration methods, inhalation technics, inhalation aids].
Explore the source record for details and available documents.
Administration, Inhalation↗
[New trend in asthma therapy. Already early administration of inhaled corticoids--but low dosage when possible for long-term treatment].
Explore the source record for details and available documents.
Administration, Inhalation↗
Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group.
BACKGROUND AND METHODS: We conducted two multicenter, double-blind, placebo-controlled trials of intermittent administration of inhaled tobramycin in patients with cystic fibrosis and Pseudomonas aeruginosa infection. A total of 520 patients (mean age, 21 years) were randomly assigned to receive either 300 mg of inhaled tobramycin or placebo twice daily for four weeks, followed by four weeks with no study drug. Patients received treatment or placebo in three on-off cycles for a total of 24 weeks. The end points included pulmonary function, the density of P. aeruginosa in sputum, and hospitalization. RESULTS: The patients treated with inhaled tobramycin had an average increase in forced expiratory volume in one second (FEV1) of 10 percent at week 20 as compared with week 0, whereas the patients receiving placebo had a 2 percent decline in FEV1 (P<0.001). In the tobramycin group, the density of P. aeruginosa decreased by an average of 0.8 log10 colony-forming units (CFU) per gram of expectorated sputum from week 0 to week 20, as compared with an increase of 0.3 log10 CFU per gram in the placebo group (P<0.001). The patients in the tobramycin group were 26 percent (95 percent confidence interval, 2 to 43 percent) less likely to be hospitalized than those in the placebo group. Inhaled tobramycin was not associated with detectable ototoxic or nephrotoxic effects or with accumulation of the drug in serum. The proportion of patients with P. aeruginosa isolates for which the minimal inhibitory concentration of tobramycin was 8 microg per milliliter or higher increased from 25 percent at week 0 to 32 percent at week 24 in the tobramycin group, as compared with a decrease from 20 percent at week 0 to 17 percent at week 24 in the placebo group. CONCLUSIONS: In a 24-week study of patients with cystic fibrosis, intermittent administration of inhaled tobramycin was well tolerated and improved pulmonary function, decreased the density of P. aeruginosa in sputum, and decreased the risk of hospitalization.
Administration, Inhalation↗
Long term clinical comparison of single versus twice daily administration of inhaled budesonide in moderate asthma.
BACKGROUND: Inhaled steroids are widely used in the treatment of mild to moderate asthma. However, long term compliance with inhaled steroids is poor and administration of a single daily dose may improve compliance. METHODS: A double blind, randomised study was performed to determine whether inhaled steroids given once daily at bedtime are as efficacious as a twice daily regimen in the long term maintenance of moderate asthmatic patients. Forty adults of mean age 37 years with moderate asthma (mean (SE) forced expiratory volume in one second (FEV1) 73.6 (1.4)% predicted, mean morning peak expiratory flow (PEF) 328 l/min) were randomised to receive either a twice daily dose (400 micrograms morning and bedtime) of inhaled budesonide (group A) or a once daily dose of 800 micrograms (group B) and were followed for a period of 12 months. Asthma symptom scores (assessed according to a modified Borg scale), inhaled beta 2 agonist consumption, and peak expiratory flow rates were recorded daily. Spirometry and airways responsiveness to methacholine (PC20) were measured at the end of each period of three months of treatment. RESULTS: There was no difference between the two groups at baseline and during the follow up period in the PC20 for methacholine. However, a difference was seen between the two groups in the mean daily number of beta 2 agonist inhalations (1.4 (0.1) puffs/patient/day in group A v 2.3 (0.1) in group B), the PEF variability (episodes of decrease in PEF of > 20%) (0.22 (0.01) episodes/patient/day in group A v 0.40 (0.02) in group B), and for asthma symptom scores (0.30 (0.04) in group A v 0.42 (0.06) in group B) for the 12 month period of the study. CONCLUSIONS: Although both regimens provide good clinical control, twice daily doses of 400 micrograms inhaled budesonide are more effective than a single dose of 800 micrograms at bedtime in the long term control of stable moderate asthma.
Administration, Inhalation↗
Correlation of lethal doses of industrial chemicals between oral or intraperitoneal administration and inhalation exposure.
Correlations of lethal doses of industrial chemicals between oral or intraperitoneal administration and inhalation exposure in rats and mice were investigated. LC50 values for inhalation exposure and LD50 values for oral and intraperitoneal administration were obtained from the Registry of Toxic Effects of Chemical Substances. LC50 and LD50 values were plotted on ordinate and abscissa, respectively, using logarithmic scales. A correlation coefficient of r = 0.624 (n = 146, p < 0.001) was obtained for LC50 (ppm) and LD50 (mg/kg) values with oral administration (oral LD50) in rats. This correlation was improved by converting the units of LC50 from ppm to ppm h (cumulative dose), and by converting the units of LD50 from mg/kg to mmol/kg. The correlation coefficient was r = 0.742 when ppm*hr and mmol/kg were adopted for LC50 and LD50, respectively. A similar improvement in correlation coefficients by the same unit conversion was also observed between LC50 and LD50 with intraperitoneal (i.p.) administration (i.p. LD50) in rats. Correlations between LC50 and oral LD50 in mice were also improved by the same unit conversion. The correlations between LC50 and i.p. LD50 were higher than those between LC50 and oral LD50 both in rats and mice. In these correlations, coefficients obtained in rats were greater than corresponding coefficients in mice. We calculated equations to estimate LC50 values accompanied by confidence limits from oral or i.p. LD50 values.
Administration, Oral↗
[Comparative assessment of enteral and inhaled n-butanol in laboratory animals].
Enteral and inhaled n-butanol given to albino rats was tested for toxicity in 2 series of subacute 30-day toxicological experiments. Enteral and inhalant administration caused membrano-, hepato-, adrenotoxic effects, and inhalant administration produced neurotoxic ones. The threshold dose was 0.2 mg/kg, the maximum ineffective one was 0.04 mg/kg. The threshold concentration was not established in the experiment. The less than 95% confidence limits of reference points (BMDL and BMCL), which cause a 10%-increase in the frequency of adverse reactions (blood catalase induction), were 0.052 mg/kg with enteral administration and 0.18 mg/m3 (0.076 mg/kg) on inhalation. The comparative toxicity coefficient (BMDLent/BMDLinh = 0.68) for n-butanol suggests that there is no difference in toxicity on different routes of administration.
1-Butanol↗
Model-based administration of inhalation anaesthesia. 3. Validating the system model.
BACKGROUND: We quantified the predictive performance of our computer model of the administration of inhalation anaesthesia from a Datex-Ohmeda Modulus CD circle-absorber system. METHODS: In 50 patients, desflurane anaesthesia was maintained with a fresh-gas flow (FGF) of 0.5 litres min(-1) of both nitrous oxide and oxygen, preceded by fast (n=14) or slow (n=36) induction: FGF greater than total ventilation, Group F; FGF equal to 1.0 litres min(-1), Group S. The two versions of the model studied differed in the size of their inter-tissue diffusion, as 0 (version 1) and 3% (version 2) of the cardiac output was shifted from the viscera to adipose tissue. Model performance was judged by comparing measured and predicted gas concentrations in terms of three variables for each gas concentration in each patient: root mean squared error (rmse=total error), bias (mean predicted - measured) (systematic error), and scatter (error around bias). These variables were then averaged over all patients. These measures were calculated overall, and separately for each group and each stage (1 = induction or 2 = maintenance). RESULTS: Model predictions were in reasonable to very good agreement with clinically obtained data. Version 2 performed better than version 1. Differences between groups were not demonstrated. The model performed better for stage 2, but only for desflurane. In group S, results (mean (SD); as percentages of the measured values for nitrous oxide, oxygen and desflurane) in the order rmse, bias, and scatter were for end-tidal concentrations of nitrous oxide: 8 (4), 8 (5), 2 (1)%; oxygen: 11 (4), -10 (6), 2 (1.1)%; nitrogen: 0.9 (0.6), -0.8 (0.6), 0.2 (0.1) vol%; carbon dioxide: 1.8 (0.6), 1.8 (0.6), 0.2 (0.1) vol%; desflurane, stage 2: 8 (4), 4 (7), 4 (2)%, vs 15 (6), -10 (8), 9 (4)% for stage 1. CONCLUSION: Administration of inhalation anaesthesia can be based on version 2 of this model, but must be guided by active monitoring.
Adolescent↗
Formation of DNA adducts in F-344 rats after oral administration or inhalation of [14C]methyl bromide.
The genotoxic effects of methyl bromide were investigated in a DNA-binding study. [14C]Methyl bromide was administered to male and female F-344 rats orally, or by inhalation from a closed exposure system. DNA adducts were detected in the liver, lung, stomach and forestomach. [14C]3-Methyladenine, [14C]7-methylguanine and [14C]O6-methylguanine were identified using a combination of three different methods of hydrolysing DNA, followed by HPLC or gas chromatography-mass spectrometry. After both oral and inhalation exposure, the highest levels of methylated guanines, especially those of [14C]O6-methylguanine, were found in the stomach and forestomach of the rats. These results clearly demonstrate a systemic DNA-alkylating potential of methyl bromide.
Administration, Inhalation↗
[Modes of administration of inhaled corticosteroids in mild to moderate persistent asthma].
Inhaled corticosteroids are the treatment of choice for asthma. However, poor compliance by patients is one of the principal difficulties forced by clinicians. Thus, it seems important to propose the minimal daily number of doses. This study has compared the various modes of administration of inhaler corticosteroids and was carried out in patients with mild to moderate persistent asthma. Thus, comparing two to four doses per day shows an identical efficacy if the dose is less than 800 micrograms per day. At higher doses only two studies have been carried out and there are discordant results. The studies compare two doses versus one single dose per day and equally disagree with numerous works in favor of a single daily dose. In the single study carried out for at least twelve months the twice daily dose was the most effective. Thus it seems reasonable to suggest a single dose for mild persistent asthmatics. For moderate persistent asthmatics the choice between a single or twice daily dose would depend on the therapeutic compliance of the patient.
Administration, Inhalation↗
Relative bioavailability of salbutamol to the lung following inhalation when administration is prolonged.
AIMS: Urinary salbutamol post-inhalation has been shown to be an index of lung deposition. The possibility of using the urinary method for prolonged periods of inhalation (such as nebulized therapy) has been evaluated. METHODS: On separate study days volunteers received salbutamol 5 x 100 microg via either oral administration (ORAL), oral with 5 g oral charcoal (ORAL + C), inhaled from a metered dose inhaler (MDI) or MDI plus 5 g oral charcoal (MDI + C). Each dose was separated by 2 min, i.e. administration time of 8 min. Urine samples were provided at 0, 30, 40, 60 and 120 min postdose. Also seven subjects inhaled 5x100 microg doses from the MDI on five separate occasions and provided urine 0-30 min post dose. RESULTS: No salbutamol was detected in urine samples following ORAL + C. The mean (s.d.) amounts of salbutamol excreted in the urine in the first 30 min post ORAL, MDI and MDI + C were 0.42 (0.55), 11.01 (3.77) and 11.60 (3.68) microg, respectively. The ratio of urinary salbutamol following MDI and MDI + C to ORAL in the 0-30 min collection period was 26.2 and 27.8, and between 30 and 40 min postdose was 5.1 and 4.7, respectively. There was no difference between urinary salbutamol over the first 30 min following MDI and MDI + C with a mean ratio (90% confidence interval) of 95.6 (84.0, 107.2). The mean (s.d.) coefficient of variation for the 30 min urinary salbutamol elimination following inhalation of 5 x 100 microg doses from the MDI by seven subjects (on 5 separate study days) was 9.4 (2.3)%. CONCLUSIONS: The 30 min urinary salbutamol method can be used for an inhalation period of up to 8 min to identify the relative bioavailability to the lung. Samples taken after this time period are affected by excretion of the oral absorbed fraction. Most nebulisers deliver their dose within this administration time.
Administration, Inhalation↗
Metabolism of verapamil in cultures of rat alveolar epithelial cells and pharmacokinetics after administration by intravenous and inhalation routes.
Administration of therapeutic entities by inhalation opens new possibilities for drug entry into systemic circulation, but this requires passage through the alveolar epithelium. Little is known about the pulmonary metabolism of verapamil. Specifically, this cardiovascular drug suffers from extensive first pass metabolism. We therefore evaluated the metabolism of verapamil in cultured alveolar epithelium and compared findings with results after administration by inhalation and intravenous routes. Specifically, cell culture of alveolar epithelium was characterized by gene expression of surfactant proteins A, B, C, and D, by immunohistochemistry of surfactant protein C, by staining for laminar bodies, and by gene expression of cytochrome P450 monooxygenases. During 6 days of culture expression, all cellular differentiation markers were obvious, albeit at different levels. With testosterone as substrate, we found alveolar epithelial cells to produce several stereo- and site-specific hydroxylation products. This provided evidence for metabolic competence of cultured alveolar epithelial cells. With verapamil as substrate, only limited production of metabolites was observed in cell culture assays, and similar results were recorded after administration by inhalation and intravenous routes. Likewise, elimination of verapamil from lung tissue and plasma was similar by both routes of administration. In conclusion, administration of verapamil by inhalation-abrogated extensive first pass metabolism frequently seen after oral application, and this may well be extended to the development of drugs with similar pharmacokinetic defects.
Administration, Inhalation↗
Comparative safety and efficacy of single or twice daily administration of inhaled beclomethasone in moderate asthma.
OBJECTIVES: In the treatment of stable mild to moderate asthma, twice-daily administration of inhaled steroids may allow adequate control of the asthma; however, comparisons of the efficacy of once- or twice-daily administration brought contradictory results. This study is a randomized, double-blind crossover trial, set to determine if inhaled beclomethasone dipropionate given once daily in the late afternoon or at bedtime can be as effective as a twice-daily regimen in the treatment of moderate asthma. DESIGN: Subjects were randomly assigned to 3 different dosing regimens of inhaled beclomethasone: (1) regimen A, a twice-daily dose of 500 micrograms in the morning and at bedtime; (2) regimen B, a single dose of 1,000 micrograms in the late afternoon; and (3) regimen C, a single dose of 1,000 micrograms at bedtime. PATIENTS AND PARTICIPANTS: Enrolled in the study were 42 subjects who required 500 micrograms of inhaled beclomethasone dipropionate twice daily to control symptoms of asthma and to minimize use of beta 2-adrenergic agonists, according to criteria suggested in a recent international consensus on asthma therapy. Prior to receiving therapy with inhaled steroids, all of these patients either had chronic symptoms of asthma that required administration of a short-acting beta 2-agonist at least twice per day, or had nocturnal asthma symptoms at least once per week. THERAPY: After a 2-week baseline evaluation, each subject was given the 3 treatment regimens in randomized order, each for a period of 4 weeks. Subjects were asked to record daily symptoms of asthma and peak expiratory flows in the morning and evening. At the end of each treatment period, spirometric data and airway responsiveness to methacholine were measured. MEASUREMENTS AND RESULTS: Thirty-seven subjects completed the study. No significant difference was found among the 3 treatment regimens for asthma symptoms, FEV1, the provocative concentration of methacholine causing a 20 percent decrease in the FEV1 (PC20) (geometric means, 1.41, 1.09, and 1.09 mg/ml), and mean morning and evening peak expiratory flow rates (PEFR). The plasma cortisol level and the adrenocorticotropic hormone (ACTH) response were not significantly different among treatments, nor were side effects, which were minimal. CONCLUSION: In moderate asthma controlled with a twice-daily dose of inhaled beclomethasone, a single total daily dose administered in the late afternoon or in the evening provides as good control of asthma for 2 months.
Administration, Inhalation↗
Inhalation MR lymphography: a new method for selective enhancement of the lung hilar and mediastinal lymph nodes.
On MR lymphography, a new approach to the lung hilar and mediastinal nodes was developed in an animal model. Five rabbits were made to inhale iron colloid (cideferron) that was nebulized to aerosol. Two days after inhalation of the agent, the mediastinal lymph nodes decreased in signal on SE 2000/30 and SE 2000/60 images and proved to have iron on histological evaluation, whereas the popliteal nodes did not have any iron. Experimental results indicate that inhalational administration can deliver the agent to the pulmonary lymphatic system and has the potential of lung hilar and mediastinal MR lymphography.
Administration, Inhalation↗