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Effects of inhaled furosemide on exertional dyspnea in chronic obstructive pulmonary disease.

The aim of this study is to investigate the effects of inhaled furosemide on the sensation of dyspnea produced during exercise in patients with stable chronic obstructive pulmonary disease (COPD). In a double-blind, randomized, crossover study we compared the effect of inhaled furosemide on dyspneic sensation during exercise testing with that of placebo. Spirometry and incremental and constant-load exercise testing were performed after inhalation of placebo or furosemide on 2 separate days in 19 patients with moderate or severe COPD. Subjects were asked to rate their sensation of respiratory discomfort using a 100-mm visual analog scale. There was significant improvement in mean FEV1 and FVC after inhalation of furosemide (p = 0.038 and 0.005, respectively) but not after placebo. At standardized exercise time during constant-load exercise testing but not during incremental exercise, the mean dyspneic visual analog scale score was lower after inhalation of furosemide compared with placebo (33.7 +/- 25.2 vs. 42.4 +/- 24.0 mm, respectively, p = 0.014). We conclude that inhalation of furosemide alleviates the sensation of dyspnea induced by constant-load exercise testing in patients with COPD and that there is significant bronchodilation after inhalation of furosemide compared with placebo in these patients.

Administration, Inhalation↗

Young and elderly type 2 diabetic patients inhaling insulin with the AERx insulin diabetes management system: a pharmacokinetic and pharmacodynamic comparison.

The objective of this study was to compare the pharmacokinetics (PK), pharmacodynamics (PD), and safety of inhaled insulin delivered by the AERx iDMS in young and elderly patients with type 2 diabetes. Twenty-seven young (18-45 years, inclusive) and 28 elderly (>/= 65 years) type 2 diabetic patients were enrolled in this study. A single inhalation of 1.57 mg (45 IU, effect comparable to 6 s.c. units) of regular human insulin was administered to each patient on each of 2 dosing days, and blood samples were drawn up to 360 minutes postdosing to generate the PK/PD curves. AUC(0-360 min) and Cmax values of inhaled insulin were comparable between young and elderly subjects (p = 0.476 for AUC(0-360 min) and p = 0.414 for Cmax). However, the elderly group had significantly less glucose reduction, as indicated by plasma glucose AOC(0-360) (area over the curve) values (p = 0.011). The intrasubject variability of inhaled insulin using the AERx iDMS was similar for young and elderly subjects and was similar to what has previously been reported for soluble insulin administered subcutaneously. Inhaled insulin was well tolerated in these patients, and no changes in pulmonary function tests were observed. A single inhalation of insulin using the AERx iDMS demonstrated comparable insulin PK profiles between the elderly and young type 2 patients but less glucose reduction in the elderly. Based on these results, elderly diabetic patients may need to inhale more insulin than young patients to achieve similar glycemic control. Long-term clinical trials using the AERx device will be useful to study age-related differences.

Administration, Inhalation↗

Estimating mass balance for inhaled drugs in humans: an example with a VLA-4 antagonist, IVL745.

IVL745 is an inhaled VLA-4 antagonist developed for the treatment of asthma. Following inhalation (Inh), a fraction of the drug is deposited in the oropharynx, and the rest is deposited in the lungs. For inhaled drugs, it is technically and ethically difficult to formulate and administer radiolabeled drugs. Hence, if the drug is metabolically stable in the lungs, mass balance and metabolism of inhaled drugs, such as IVL745, can be determined by administering radiolabeled intravenous (IV) and oral drugs and by comparing with the data following Inh administration. The study was a three-period crossover design in 6 healthy subjects to evaluate the absorption, distribution, metabolism, and elimination following IV and oral administration of (14)C-IVL745 (4 mg/50 microCi) and inhaled (10-mg) dose. Serial sampling of blood and excreta was performed maximally up to 168 hours postdose. Plasma IVL745 concentrations were determined using a liquid chromatography tandem mass spectrometry (LC/MS/MS) method with a minimum quantifiable limit of 10 pg/mL. Overall, the drug was safe and well tolerated. The recovery of the radioactive dose varied from 94.8% to 117% for both IV and oral administration. Following IV administration, 90.2% of the radioactive dose was recovered in the feces, suggesting extensive biliary excretion of the drug. After oral administration, 99.7% of the radioactivity was recovered in the feces, and no radioactivity was detected in plasma, suggesting lack of absorption of the drug. Negligible (14)C-radioactivity concentrations were observed in the red blood cell fractions. The mean t(1/2) values were 1.6, 1.5, and 4.4 hours following IV, oral, and Inh administration, respectively. The oral bioavailability of IVL745 was low (< 2%), and the inhaled bioavailability was 26%. The volume of distribution at steady state (V(ss)) was low (19.0 L). The predicted blood clearance of IVL745 was 86 L/h, which was comparable to the commonly used liver blood flow value of 90 L/h. Only a minor fraction of the dose was excreted in the urine with low to moderate renal clearance. The parent drug accounted for 77% to 89% of the dosed radioactivity in excreta. Two major metabolites observed in excreta were mono-o-desmethyl IVL745 and di-o-desmethyl IVL745. The data showed that the drug had negligible oral bioavailability, low oral absorption, 26% inhaled bioavailability, low extent of metabolism, high biliary excretion, and low renal clearance. This knowledge may aid in the prediction of potentially relevant drug-drug interactions and dosing adjustments in high-risk populations for IVL745.

Administration, Inhalation↗

Inhalation exposure technology, dosimetry, and regulatory issues.

Inhalation toxicology technology has provided the scientific community with important advances in studies of inhaled toxicants. These advances include new and more efficient exposure systems (e.g., flow-past nose-only exposure systems), and improved approaches to inhalation chamber environmental control (e.g., temperature, humidity, air quality). Practical problems and approaches to testing and operating inhalation exposure systems and the advantages and disadvantages of the major inhalation exposure types (e.g., whole-body, nose-only) are discussed. Important aspects of study design, such as high level particulate exposures resulting in large lung burdens (e.g., greater than or equal to 2 mg/g of lung), slowed pulmonary clearance rates, and nonspecific toxicity are considered, along with practical issues of comparative dosimetry. Regulatory guidelines have continued to present challenges in designing and conducting acute, subchronic, and chronic inhalation studies. The important regulatory issue of performing acute inhalation toxicity studies at high aerosol concentrations and "respirable" particle size distribution is discussed.

Administration, Inhalation↗

Inhaled antibiotics in cystic fibrosis: a review.

OBJECTIVE: To provide an overview of aerosol drug therapy, including physical considerations and aerosol drug delivery systems, and to review clinical experience with inhaled antibiotics in cystic fibrosis (CF) when used as adjunctive therapy to intravenous therapy for acute pulmonary exacerbations and chronic, suppressive therapy. DATA SOURCES: A MEDLINE search (1966-1995) of English-language literature describing the use of inhaled antibiotics for the management of CF. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Pertinent information as judged by the authors was selected for discussion. DATA SYNTHESIS: The use of inhaled antibiotics as adjunctive therapy to systemic therapy for acute exacerbations did not improve pulmonary function tests, increase hospital discharge rate, or permanently eradicate sputum Pseudomonas. Clinical trials of inhaled antibiotics as suppressive therapy yielded variable results. Individually, four trials documented a significant improvement in pulmonary function, three trials documented a slower decline in pulmonary function, and four trials reported a reduced frequency of hospitalizations. However, the trials were unable to collectively document a prolonged beneficial effect of inhaled antibiotics on pulmonary function, sputum bacterial density, and frequency of hospitalizations. CONCLUSIONS: Clinical trials conducted thus far suggest no role for inhaled antibiotics in the treatment of acute pulmonary exacerbations in patients with CF. Aerosolized antibiotics used as suppressive therapy may be useful in certain patients, but their use should be limited to select patients based on individual response to therapy. Additional long-term, well-controlled trials of inhaled antibiotics as suppressive therapy are needed before routine use can be recommended.

Administration, Inhalation↗

Effect of nitric oxide inhalation on respiratory system resistance in chronic obstructive pulmonary disease.

Nitric oxide (NO) has been identified as a neurotransmitter of nonadrenergic noncholinergic bronchodilator nerves. To investigate whether inhaled NO exerts a bronchodilator effect in patients with chronic obstructive pulmonary disease (COPD), we measured the resistance of the respiratory system, using the forced oscillation technique, while breathing NO. Eight patients with COPD (7 men and 1 woman; aged 66 +/- 7 yrs (mean +/- SD); forced expiratory volume in one second (FEV1) 37 +/- 17% of predicted) and eight healthy subjects (7 men and 1 woman; 33 +/- 4 yrs; FEV1 108 +/- 14% pred) were studied. Nitric oxide, at a concentration of 40 parts per million (ppm) in air, was inhaled for 20 min. Total resistance (Rrs) and reactance (Xrs) of the respiratory system, arterial oxygen saturation, heart rate, tidal volume, and breathing frequency were continuously recorded at baseline, and during and after ceasing NO inhalation. Methaemoglobin levels were additionally measured in healthy subjects. At baseline, patients with COPD showed higher Rrs than healthy subjects (Rrs at 10 Hz (Rrs,10) 4.97 +/- 2.19 vs 2.29 +/- 0.65 hPa.L-1.s). During NO inhalation, no significant change in Rrs or in Xrs was observed. Mean variation in Rrs,10 while breathing NO was negligible and similar in the two groups (-0.10 +/- 0.13 hPa.L-1.s in COPD patients and -0.02 +/- 0.13 hPa.L-1.s in healthy subjects). Moreover, there were no differences in oxygen saturation, heart rate, tidal volume and breathing frequency during NO inhalation. Methaemoglobinaemia increased at the end of NO inhalation (from 0.48 +/- 0.18 to 0.81 +/- 0.16%), and this increment remained 10 min later (0.86 +/- 0.31%). From these results, we conclude that inhaled nitric oxide, at a concentration of 40 ppm, exerts no effect on respiratory system resistance in patients with chronic obstructive pulmonary disease or in healthy subjects.

Administration, Inhalation↗

Combined smoke inhalation and body surface burns injury does not necessarily imply long-term respiratory health consequences.

This study was undertaken to assess the long-term respiratory health consequences of smoke inhalation in patients who are burns survivors. Patients with smoke inhalation resulting from domestic flame or fire were studied. Medical records were the primary source for the selection of the patients. Smoke inhalation was diagnosed on the basis of the visual appearance of the airways on the reported bronchoscopy. Patients who participated in the study were compared on important characteristics with those who did not participate. The participants were then assessed by questionnaire, physical examination, chest radiograph and pulmonary function tests. Twenty three out of 45 patients who had survived smoke inhalation participated in the study. Participants and nonparticipants were comparable with respect to gender, age, time since injury, aetiology of injury, and total body surface burned. Participants had more facial burns, more severe bronchoscopic findings of smoke inhalation and required intubation more frequently. Respiratory symptom assessment and pulmonary function tests were performed 45 +/- 23 months after smoke inhalation. Four patients reported an increase in dyspnoea, one an increase in cough and one an increase in phlegm. All the patients had pulmonary function tests and bronchial responsiveness (provocative concentration of histamine resulting in a 20% fall in forced expiratory volume in one second (PC20) > 16 mg.mL-1) within normal limits. The four patients complaining of increased dyspnoea had results within normal limits for cardiac and respiratory variables on maximal exertion. The present study indicates that, in burn patients, smoke inhalation resulting from a single domestic fire does not necessarily imply long-term respiratory health consequences.

Adult↗

In vitro comparison of the amount of salbutamol available for inhalation from different formulations used with different spacer devices.

Metered-dose inhalers (MDIs) are currently being reformulated to contain hydrofluoroalkanes (HFAs), which do not damage the Earth's ozone layer. As different formulations of inhaled drugs may behave differently when used with spacer devices, we wished to determine the amount of salbutamol available for inhalation from a conventional metered-dose inhaler (Ventolin) and a new HFA-containing formulation (Airomir), when used with two different spacers. A glass multistage liquid impinger was used to determine the amount of salbutamol delivered from the inhalers used with the Aerochamber and the Nebuhaler spacer devices. High speed video-recordings of inhaler actuation into air were made, and the speed of the aerosol and the aerosol cloud volume were measured. More salbutamol in small particles (<5 microm) was delivered from the Airomir MDI than the Ventolin MDI, when used with the Aerochamber (40.4 (95% confidence interval (95% CI) 31.2-49.6) versus 19.5 (19.0-20.0) microg) and the Nebuhaler (42.1 (36.3-47.9) versus 24.6 (23.3-25.8) microg). The aerosol cloud from the Airomir MDI was slower than the Ventolin aerosol, and 60 ms after actuation had travelled 186 mm, whereas the Ventolin aerosol had travelled 320 mm. At the same time, the Airomir aerosol occupied a smaller volume than the Ventolin MDI (251 (213-288) versus 695 (608-782) cm3). The hydrofluoroalkane formulation delivers more salbutamol than the conventional formulation when used either with the Aerochamber or Nebuhaler spacer. This may be because less drug is deposited in the spacer from the hydrofluoroalkane formulation, which is emitted from the metered-dose inhaler at a slower speed and occupies a smaller volume than the conventional formulation. The observed difference in drug delivery may be important for patients changing formulations, and in severe asthma, where high doses of salbutamol may be administered through a spacer.

Administration, Inhalation↗

Lung delivery of salbutamol by dry powder inhaler (Turbuhaler) and small volume antistatic metal spacer (Airomir CFC-free MDI plus NebuChamber).

As a worldwide ban on the use of chlorofluorocarbons (CFCs) in inhaler devices approaches, considerable attention has been focused on the production of CFC-free delivery devices. The aim of our study was to compare the delivery of salbutamol by dry powder inhaler (DPI), Turbuhaler and a CFC-free metered-dose inhaler (MDI), Airomir, used with a novel small volume metal spacer (NebuChamber). Ten healthy volunteers, mean (SEM) age 21 (0.7) yrs were studied in a randomized, single (investigator)-blind cross-over design. Single doses of 1,200 microg salbutamol, from Turbuhaler DPI and Airomir CFC-free MDI via a NebuChamber, were given as 12 sequential 100 microg inhalations over 6 min. The lung delivery of salbutamol was assessed by measuring the plasma salbutamol profile over the first 20 min after inhalation. Plasma salbutamol concentration was expressed as maximal (Cmax) and average (Cav) value. Significant differences (p<0.001) were found between the NebuChamber (N) and the Turbuhaler (T) for salbutamol Cmax and Cav. This amounted to a 1.89 fold difference (95% CI 1.56-2.22) between these devices for Cmax, and a 1.78 fold difference (95% CI 1.42-2.15) for Cav. We have demonstrated that, in vivo, salbutamol from a chlorofluorocarbon-free metered-dose inhaler given via a small volume metal spacer (NebuChamber) produces significantly greater delivery than from an efficient dry powder inhaler (Turbuhaler).

Administration, Inhalation↗

Effects of long-term inhaled corticosteroids on skin collagen synthesis and thickness in asthmatic patients.

There are only a few studies on the adverse effects of inhaled corticosteroids on the skin in asthmatic patients. Therefore, we evaluated the effect of inhaled corticosteroids on de novo collagen synthesis of skin and bone, skin thickness and the total amount of skin collagen. Twenty seven consecutive new asthmatic patients, on a moderate dose of budesonide or beclomethasone dipropionate, were invited to take part in this prospective study. Radioimmunological analyses of aminoterminal propeptides of type I and III procollagens (PINP, PIIINP, respectively) in suction blister fluid (SBF) of skin and in serum and carboxyterminal propeptide of type I procollagen (PICP) and cross-linked carbox terminal telopeptide of type I collagen (ICTP) in serum were performed at entry and after 3 and 6 months of inhaled corticosteroid treatment. Ultrasound measurements of skin thickness at two sites were performed at entry, at 3 and 6 months and after 1-2 yrs of inhaled corticosteroid treatment in 20 patients, six of whom had been prescribed one or more courses of oral corticosteroids. Skin hydroxyproline of punch biopsies was determined to measure the total amount of skin collagen (males, at entry and at 6 months). Skin thickness and the total amount of skin collagen on the abdomen were unchanged after 1-2 yrs of inhaled corticosteroid use. A slight decrease was observed in the upper arm skin thickness, especially in those subjects who had received inhaled plus oral corticosteroids. The procollagen propeptide concentrations (PINP, PIIINP) were markedly decreased in SBF at 3 months and remained at this level at 6 months. In serum, a slight decrease was seen in the PINP, PIIINP and ICTP concentrations at 3 and 6 months. In conclusion, inhaled corticosteroids decrease the collagen synthesis of skin and bone, but skin thickness and the total amount of collagen in skin are not changed markedly after 1-2 yrs of treatment.

Administration, Inhalation↗

Effect of inhaled corticosteroids on bones and growth.

Inhaled corticosteroids are recognized as the most effective anti-inflammatory therapy in patients with asthma and their early introduction is recommended by national and international guidelines. Concerns have been raised about potential adverse effects of inhaled corticosteroids on bones and growth, as these appear to be more important clinically than effects on the hypothalamic-pituitary-adrenal axis, which are more commonly measured. This review examines the effects of inhaled corticosteroids on biochemical bone markers, bone density and growth in adults and children with asthma, in view of the recent availability of a substantial amount of new clinical trial data. Examination of relevant retrospective and prospective data, involving 11 studies (1,240 patients) on biochemical bone markers and 14 studies (373 patients) on bone density over a wide dose range, have largely indicated no significant or clinically important effect on these measurements in adults or children with asthma. Markers of bone formation and resorption need to be measured concurrently for a reliable assessment of bone turnover to be made. Knemometry, measuring lower leg growth rate, is a sensitive technique for comparing the systemic activity of different inhaled corticosteroids, but does not relate to long-term growth. The majority of approximately 40 studies on inhaled corticosteroids and statural growth in children, over a wide recommended dose range, including a number of recent long-term, prospective studies, demonstrate little or no effect. Children taking above recommended doses of inhaled corticosteroids should have their growth monitored using stadiometry at least every 6 months by trained personnel. Most of the areas reviewed, particularly the relatively new areas of biochemical bone markers and bone density, require further properly controlled, long-term, prospective investigation, although the long-term value of bone markers appears limited. In summary, the data as it currently stands, suggests that doses of inhaled corticosteroids up to 1,000 microg x day(-1) in adults and 400 microg x day(-1) in children have no significant effect on bones and growth in the large majority of patients with asthma.

Administration, Inhalation↗

The contribution of the swallowed fraction of an inhaled dose of salmeterol to it systemic effects.

Salmeterol is approximately eight times as potent as salbutamol for systemic effects. This may be because the drug is eight times more potent on receptors or there may be differences in systemic bioavailability. The systemic effects of salbutamol are limited by its fairly high first-pass metabolism, but the oral bioavailability of salmeterol is unknown. The contribution of the swallowed fraction of an inhaled dose of salmeterol to its systemic effects were analysed in a randomized, double-blind, crossover study. Twelve healthy subjects were given inhaled salmeterol 400 microg, inhaled salmeterol 400 microg plus oral activated charcoal or inhaled placebo plus oral activated charcoal on three separate days. Cardiac frequency (fC), Q-T interval corrected for heart rate (QTc), plasma potassium and glucose concentrations were measured for 4 h following the inhaled drug. Salmeterol with and without oral charcoal produced significant changes for all measures compared to placebo. The magnitude of effect following salmeterol alone was significantly greater than that following salmeterol plus charcoal for fC and glucose (mean (95% confidence interval) differences 8 (2-13) beats x min(-1), 0.59 (0.04, 1.13) mmol x L(-1), respectively) and nonsignificantly greater for QTc interval and potassium concentration. The differences between salmeterol given with and without charcoal suggest that 28-36% of the systemic response to salmeterol administered from a metered-dose inhaler are due to drug absorbed from the gastrointestinal tract. Thus, most of the systemic effects are due to the inhaled fraction of the drug.

Administration, Inhalation↗

Pituitary-adrenal suppression in preterm, very low birth weight infants after inhaled fluticasone propionate treatment.

Systemic corticosteroids prescribed for treatment of pulmonary diseases in preterm, very low birth weight infants caused severe suppression of the hypothalamic-pituitary-adrenal axis and produced serious physiological and metabolic disturbances. However, the effect of inhaled corticosteroids on their pituitary-adrenal functions is not known. We prospectively evaluate the pituitary-adrenal function using the human CRH stimulation test in a cohort of very low birth weight infants at risk for hypothalamic-pituitary-adrenal axis suppression in a double blind, randomized pilot study designed for assessing the efficacy and adverse effects of inhaled fluticasone propionate in newborn preterm infants who required mechanical ventilation for treatment of respiratory distress syndrome. Twenty-five preterm (< 32 gestational weeks), very low birth weight (< 1500 g) infants were randomized to receive inhaled fluticasone propionate (n = 13) or a placebo inhaler (n = 12). The medication was given every 12 h (fluticasone propionate, 1,000 micrograms/day) for 14 days. All surviving infants had their pituitary-adrenal functions assessed by human CRH test on the following morning immediately after completion of the 2-week course. All basal (0 min) and post-stimulation (15, 30, and 60 min) plasma ACTH and serum cortisol concentrations were significantly suppressed in the inhaled fluticasone group compared to their corresponding levels in the placebo group [basal plasma ACTH concentrations (F = 6.0; P = 0.02), poststimulation plasma ACTH concentrations (F > 8.6; P < 0.01), basal serum cortisol concentrations (F = 5.6; P = 0.03), and poststimulation serum cortisol concentrations (F > 15.6; P < 0.001)]. This is the first study in very low birth weight infants that demonstrates unequivocally that cumulative high dose inhaled corticosteroids can induce moderately severe suppression of both the pituitary and adrenal glands. The systemic bioactivity is probably associated with pulmonary vascular absorption, which effectively circumvents the hepatic first pass metabolism. Until the question of safety can be adequately addressed, inhaled fluticasone propionate should be used with cautionin preterm infants.

Administration, Inhalation↗

The effect of inhaled colforsin daropate on contractility of fatigued diaphragm in dogs.

UNLABELLED: We studied the effect of inhaled colforsin daropate, a water-soluble forskolin derivative, on the contractility of fatigued diaphragm in dogs. Animals were divided into 3 groups of 8. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20-Hz stimulation applied for 30 min. Immediately after the end of the fatigue-producing period, Group 1 received inhaled vehicle, Group 2 received inhaled colforsin daropate 0.1 mg/mL, and Group 3 received inhaled colforsin daropate 0.2 mg/mL. We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). After fatigue was produced, in each group, Pdi at low-frequency (20-Hz) stimulation decreased from baseline values (P < 0.05), and there was no change in Pdi at high-frequency (100-Hz) stimulation. In Groups 2 and 3, during colforsin daropate inhalation, Pdi at both stimuli increased from fatigued values (P < 0.05). The increase in Pdi was significantly larger in Group 3 than in Group 2. The integrated electrical activity of the diaphragm did not change in any group. We conclude that inhaled colforsin daropate causes an increase in contractility of fatigued canine diaphragm in a dose-related fashion. IMPLICATIONS: Diaphragmatic fatigue may contribute to the development of respiratory failure. Inhaled colforsin daropate improves, in a dose-dependent manner, the contractility of fatigued diaphragm in dogs.

Administration, Inhalation↗

Inhibitory effects of the fragrance inhalation of essential oil from Acorus gramineus on central nervous system.

The present study was designed to evaluate central inhibitory effects of the essential oil from Acori graminei Rhizoma (AGR), the dry rhizomes of Acorus gramineus SOLANDER (Araceae) upon fragrance inhalation (aroma therapy). Preinhalation of the oil markedly delayed the appearance of pentylenetetrazole-induced convulsion. Furthermore, inhalation impressively inhibited the activity of gamma-aminobutyric acid (GABA) transaminase, a degrading enzyme for GABA as the inhalation period was lengthened. The GABA level was significantly increased and glutamate content was significantly decreased in mouse brain by preinhalation of the essential oil. The above results suggest that the anticonvulsive effect of this AGR oil is originated by the enhancement of GABA level in the mouse brain, because convulsion depends partially on GABA concentration which can be properly preserved by inhibiting GABA transaminase. Moreover, fragrance inhalation progressively prolonged the pentobarbital-induced sleeping time as inhalation time was lengthened. Ten hour inhalation corresponded almost to the effect (145% increase) of oral administration (60 mg/kg). This sedative effect after inhalation or oral administration of AGR essential oil suggests that this oil may act on the CNS via the GABAergic system. The inhibitory activity of preinhalation of the essential oil on lipid peroxidation, to which the anticonvulsive action is attributed, also supported the above results, confirming and amplifying our previous reports on the CNS inhibitory effects of AGR.

Acorus↗

Effects of inhaling the vapor of Lavandula burnatii super-derived essential oil and linalool on plasma adrenocorticotropic hormone (ACTH), catecholamine and gonadotropin levels in experimental menopausal female rats.

The effects of inhaling the vapor of Lavandula burnatii super-derived essential oil and one of the main components of lavender oil, linalool on plasma adrenocorticotropic hormone (ACTH), catecholamine and gonadotropin levels in menopausal model rats under ether-inhalation were studied. The increased plasma ACTH levels induced by ether-inhalation tended to decrease by pre-inhalation of Lavandula burnetii super and linalool vapor was induced the decrease of ACTH level. The decrease in adrenaline, noradrenaline and dopamine levels induced by ether-inhalation tended to recover, especially, the dopamine level significantly recovered to the normal level by the inhalation of Lavandula burnetii super and linalool vapor. However, the increased plasma gonadotropin levels in ovariectomized retired female rats (menopausal model rats) was significantly decreased by the inhalation of linalool. These results suggest that lavender oil or one of the main components, linalool may contribute to relieving tension and may be applicable to the treatment of menopausal disorders in human beings.

Acyclic Monoterpenes↗

Effect of surface covering of lactose carrier particles on dry powder inhalation properties of salbutamol sulfate.

The effect of the surface covering of lactose carrier particles on the dry powder inhalation properties of salbutamol sulfate was investigated. Lactose carrier surfaces were covered with sucrose tristearate (J-1803F) by a high-speed elliptical-rotor-type powder mixer (Theta-Composer). In the present study, drug/carrier powder mixtures were prepared consisting of micronized salbutamol sulfate and lactose carriers with various particle surface conditions prepared by surface covering. These powder mixtures were aerosolized by a Jethaler), and the in vitro inhalation properties of salbutamol sulfate were evaluated by a twin impinger. Compared with the powder mixed with uncovered lactose carrier, the in vitro inhalation properties of the powder mixture prepared using the surface covering lactose carrier were significantly different, showing that the in vitro inhalation properties of salbutamol sulfate were improved. In vitro inhalation properties increased with the percentage of J-1803F added. Using this surface covering system would thus be valuable for increasing the inhalation properties of dry powder inhalation with lactose carrier particles.

Administration, Inhalation↗

Effects of surface processing of lactose carrier particles on dry powder inhalation properties of salbutamol sulfate.

The effects of the surface processing of lactose carrier particles on the dry powder inhalation properties of salbutamol sulfate were investigated. Lactose carrier particles were processed using a high-speed elliptical-rotor-type powder mixer (Theta-Composer). In the present study, drug/carrier powder mixtures were prepared, consisting of micronized salbutamol sulfate and coarse lactose carriers with various particle surface conditions prepared by surface processing. These powder mixtures were aerosolized by a Jethaler, and the in vitro inhalation properties of salbutamol sulfate were evaluated with a twin impinger. Compared with those of the powder mixed with unprocessed lactose carriers, the in vitro inhalation properties of the powder mixture prepared using the surface processed lactose carriers were significantly different, showing that the in vitro inhalation properties of salbutamol sulfate were improved. The in vitro inhalation properties increased with the rotor rotation rate. Using this surface processing system would thus be valuable for increasing the inhalation properties of dry powder inhalation with lactose carrier particles.

Administration, Inhalation↗