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At least 37 records · Page 2Linked to original sources
PubMed2000

The inhaled administration of KF19514, a phosphodiesterase 4 and 1 inhibitor, prevents antigen-induced lung inflammation in guinea pigs.

We examined in this study the effect of KF19514, a phosphodiesterase 4 and 1 inhibitor, on antigen-induced lung inflammation by inhaled administration in guinea-pigs. It was previously reported that inhaled KF19514 prevented antigen-induced bronchoconstriction and platelet-activating factor (PAF)-induced lung inflammation. In fact, a variety of factors other than PAF are related to lung inflammation in real subjects with asthma. Guinea-pigs were actively sensitized by exposure to ovalbumin (OA). Fifteen to 20 days later, the guinea pigs were challenged by exposure to aerosols of five successively increasing concentrations of OA (0.01, 0.1, 0.5, 1 and 5 mg/ml). Bronchoalveolar lavages (BALs) were performed 24 h after the antigen challenge, and airway hyperresponsiveness to acetylcholine (ACh) was studied 24 h after the challenge by measuring lung resistance and dynamic compliance. Ovalbumin antigen challenge produced a marked and significant eosinophil accumulation in the BAL fluids and airway hyperresponsiveness to ACh 24 h after the challenge. Inhaled KF19514 (0.01-0.1%) inhibited the eosinophil accumulation significantly and dose-dependently but inhaled rolipram (0.01-0.1%) and aminophylline (0.1-1%) did not. In addition, the development of airway hyperresponsiveness was prevented by inhaled KF19514 (0.01%) but not by inhaled rolipram (0.01%) and aminophylline (0.1%). Based on these data, KF19514 was suggested to be a promising drug in the treatment of asthma by local administration to the lung.

Acetylcholine↗
PubMed1990

Survival after intramuscular or inhalation administration of gentamicin in neutropenic guinea pigs infected by Klebsiella pneumoniae.

Guinea pigs were infected by intranasal administration of Klebsiella pneumoniae on day 7 after irradiation with a dose of 4 Gy and treated on days 8-10 by gentamicin 4 mg/kg bd im or by inhalation leading to estimated systemically absorbed doses of 5.9 mg/kg/day. All animals died; however, gentamicin treatment significantly (P less than 0.05, Fisher's exact test) delayed death in the specific time intervals: 7-13 days (with the exception of day 11) and 12-26 days after im and inhalation administration respectively. Comparison of the two treatments by Fisher's exact test showed a significant advantage (P less than 0.05) for im vs inhalation treatment on days 9 and 10 only. The log rank test gave somewhat different results in that the delay of death after im administration was highly significantly (P less than 0.002) different from control whereas results after inhalation were not significantly different from control (P = 0.06). Moreover, according to the log rank test, im administration delayed death significantly (P = 0.04) better than inhalation. In conclusion these data do not show any advantage of inhalation over im administration for treatment of experimental pneumonia, indeed they are compatible with im administration being marginally more effective.

Administration, Inhalation↗
PubMed1995

Pharmacokinetic and pharmacodynamic evaluation of triamcinolone acetonide after intravenous, oral, and inhaled administration.

Triamcinolone acetonide (TCA) is a corticosteroid that is frequently used in the treatment of asthma. After inhalation, TCA can become systemically available when the inhaled formulation is swallowed, causing undesirable systemic effects. A clinical study was conducted to determine the systemic side effects of TCA after intravenous (2 mg as phosphate ester), oral (5 mg), and inhaled (2 mg) administration. Blood samples were collected at appropriate times over 24 hours, and TCA concentrations in plasma were measured by high-performance liquid chromatography and radioimmunoassay. Free drug concentrations were determined by ultrafiltration for correlating pharmacokinetics and pharmacodynamics. The free fraction of TCA (+/- standard deviation) was 29.0 +/- 1.3% and was independent of the investigated concentration range up to 1,000 ng/mL. Pharmacodynamic parameters were determined by monitoring lymphocytes, granulocytes, and cortisol. Pharmacokinetic/pharmacodynamic modeling was performed using a modified Emax model for lymphocytes and granulocytes. A novel linear release rate model was used to characterize the cortisol data. The E50 values determined from all three pharmacodynamic endpoints were not significantly different for the three treatments, indicating that these effects can be explained based on systemic steroid concentrations.

Administration, Inhalation↗
PubMedDate not supplied

In vitro evaluation of the effect of metered-dose inhaler administration technique on aerosolized drug delivery.

The administration of aerosolized metered-dose inhalers (MDIs) to mechanically ventilated patients is labor intensive due to the large number of activations required and the currently recommended 30- to 60-second "wait and shake" between each puff. No studies have been published that assess the relationship between this delay between puffs and drug delivery. To address this issue, we conducted an in vitro, randomized, single-blind study using fenoterol MDI containing technetium-99m pertechnetate. Four modes of MDI administration were tested in triplicate by random sequence. Eight activations of the MDI were performed for each mode according to the following procedures: rapid succession (5 sec apart); 30-second intervals and shaking MDI between two rapid activations; 30-second intervals and shaking between each activation; and 60-second intervals and shaking between each activation. Two closed in vitro systems were designed to collect and measure the radiolabeled aerosol. In the first system, the MDI was activated into a plastic collection container; with the second system, the MDI was administered through an aerosol holding chamber with attached circuit filter positioned on the inspiratory line of the ventilator circuit. Sixty-second intervals between each activation were not tested with the second system. Radioactivity was measured before and after each mode of testing. No difference was found between the various modes of administration other than a 14% decrease in the amount of radioactivity released with the 60-second waiting period between puffs, compared with their rapid succession when using the plastic collection container system. Our results support the hypothesis that the delay after each activation of a MDI may not be necessary.

Administration, Inhalation↗
PubMed1995

Pharmacokinetics of triamcinolone acetonide after intravenous, oral, and inhaled administration.

The pharmacokinetics of triamcinolone acetonide were studied after intravenous (2 mg), oral (5 mg), and inhaled (2 mg) administration. Triamcinolone acetonide concentrations were measured in plasma by high-performance liquid chromatography/radioimmunoassay. After intravenous administration, triamcinolone acetonide was eliminated with a total body clearance of 37 L/h and a half-life of 2.0 hours. The volume of distribution was 103 L, and oral bioavailability averaged 23%. Absorption was rapid, achieving maximum triamcinolone acetonide levels of 10.5 ng/mL after 1 hour. After inhalation, bioavailability averaged 22% with maximum levels of 2.0 ng/mL observed after 2.1 hours. The resulting systemic levels for all three treatments caused a significant decrease in the number of lymphocytes in blood.

Administration, Inhalation↗
PubMed1991

Autoradiographic examination of the organ distribution of 14C-labelled pentamidine in rats after intravenous and inhaled administration.

The organ distribution of 14C pentamidine was studied in Sprague Dawley rats by means of whole-body autoradiography following intravenous and inhaled application of pentamidine (Pentacarinat, CAS 140-64-7). The distribution time after intravenous administration of 5 mg pentamidine per kg rat was 30 min, 6 h, 24 h, and 7 days, respectively. The corresponding times after administration of aerosolized pentamidine were 30 min and 24 h. The distribution of radioactivity was also determined by measuring radioactivity in punch specimens of 100 microns sections. Besides renal excretion, the excretion of pentamidine in the bile and via the salivary glands was assessed by autoradiography. Further target organs included the spleen and the bone marrow. As early as after 30 min no radioactivity was detectable in the blood vessels. A lack of radioactivity in the brain tissue with accumulation of pentamidine in the meninges suggests that pentamidine does not cross the blood/brain barrier. Following intravenous administration the lung uptake of pentamidine was relatively low. However, increased drug concentrations were recorded in the bronchial system. The elimination time of pentamidine from the target organs was long. Lung pentamidine concentrations remained almost unchanged for a period of 7 days. After inhaled administration high levels of pentamidine were measured in the lung. 14C pentamidine was also located in the oropharyngeal and gastrointestinal tract, the drug stemming from pentamidine ingested or licked off the skin by the animals. No further target organs were verifiable. From the pharmacological point of view, these studies prove the advantages of pentamidine aerosol in the treatment of Pneumocystis carinii pneumonia (PCP) and provide information on extrarenal excretion mechanisms and deep compartments.

Administration, Inhalation↗
PubMed1997

Efficacy of metered-dose inhaler administration of albuterol in intubated infants.

STUDY OBJECTIVE: To compare the safety and efficacy of metered-dose inhaler (MDI) albuterol to nebulized (NEB) albuterol administration. DESIGN: A randomized, triple-blinded, crossover study. SETTING: A pediatric ICU in a tertiary care children's hospital. PATIENTS: Eleven intubated infants with bronchiolitis. INTERVENTIONS: Subjects received four puffs of MDI albuterol (360 microg) and 3 mL of NEB saline solution placebo or 0.3 mL of NEB albuterol (1.5 mg) and MDI saline solution placebo. Each set of albuterol and saline solution placebo was administered after direct attachment of delivery device to the endotracheal tube and bag-valve system. Subjects received the opposite sequence 4 h after the initial sequence. The second sequence was given first the next day, and the first sequence was administered 4 h later. MEASUREMENTS AND RESULTS: Respiratory system compliance and resistance were measured at baseline and 30 min, 1 h, 2 h, and 4 h after each set of placebo and albuterol. There was an appreciable improvement in compliance and resistance for up to 2 h following both methods of administration. However, the degree of improvement was not significantly different (p>0.05) between the two methods. Neither method caused a significant change in resistance when measured at 4 h after albuterol/placebo administration. No evidence of toxicity was detected. CONCLUSIONS: MDI-administered albuterol is as safe and efficacious as nebulized-administered albuterol in intubated infants with bronchiolitis. Generalizability of these results is limited by differences in drug delivery with different brands of nebulizers and spacers and sites of attachment.

Administration, Inhalation↗
PubMed2000

A study comparing the clinical pharmacokinetics, pharmacodynamics, and tolerability of triamcinolone acetonide HFA-134a metered-dose inhaler and budesonide dry-powder inhaler following inhalation administration.

The impending phaseout of chlorofluorocarbons as propellants in pressurized metered-dose inhalers used in the treatment of asthma has resulted in the development of alternative devices to deliver drug to the pulmonary airways. These alternative devices include metered-dose inhalers using environmentally friendly hydroflurocarbon propellants and breath-actuated dry-powder inhalers. The purpose of this study was to compare the single- and multiple-dose pharmacokinetics, pharmacodynamics, and tolerability of a newly developed hydroflurocarbon formulation of triamcinolone acetonide (Azmacort HFA 225 mcg Inhalation Aerosol) to that of the dry-powder formulation of budesonide (Pulmicort Turbuhaler 200 mcg). This three-way crossover study used 18 normal healthy subjects each receiving a 675 mcg dose of triamcinolone acetonide, 600 mcg dose of budesonide, or placebo twice a day for 5 days. Serial plasma samples were collected after the first and last dose of test medication for pharmacokinetic analysis. Pharmacodynamics were assessed by changes in hypothalamic-pituitary-adrenal axis function as measured by 8 a.m. serum cortisol, 24-hour overnight serum cortisol AUC(0-24), and 24-hour urinary-free cortisol after the last evening dose of test drug. Tolerability was assessed through physical examinations, vital signs, 12-lead ECG, routine clinical labs, and adverse events recording. Both compounds were systemically absorbed. However, no significant drug accumulation was noted with chronic dosing. Chronic dosing did result in a statistically significant 20% reduction in basal 24-hour serum cortisol AUC(0-24) for both compounds. There were no clinically significant abnormalities in physical examination, vital signs, 12-lead ECG, or routine clinical labs noted during the study. Overall, the study drugs were well tolerated, with adverse events characterized as mild to moderate in severity.

Administration, Inhalation↗
PubMed1996

Serum albuterol levels in mechanically ventilated patients and healthy subjects after metered-dose inhaler administration.

In mechanically ventilated patients, systemic blood levels of inhaled drugs reflect absorption from the lower respiratory tract alone since, unlike nonintubated patients, oropharyngeal and gastrointestinal absorption cannot occur. To determine the efficiency of aerosol administration by a metered-dose inhaler (MDI), we measured serum albuterol levels after administration by a MDI and spacer to nine mechanically ventilated patients (10 puffs) and to 10 healthy subjects (six puffs). Serum albuterol levels (+/- SEM) quantitated by high-performance liquid chromatography and electrochemical detection were: 0.09 +/- 0.04 mg/ml/puff at baseline, 0.66 +/- 0.10 at 5 min, 0.98 +/- 0.10 at 10 min, 0.56 +/- 0.08 at 15 min, and 0.37 +/- 0.03 at 30 min in mechanically ventilated patients versus zero at baseline, 0.89 +/- 0.12 at 5 min, 1.27 +/- 0.13 at 10 min, 0.84 +/- 0.09 at 15 min, and 0.53 +/- 0.07 at 30 min in control subjects (p > or = 0.07 at 5, 10, and 30 min; p < or = 0.05 at baseline and at 15 min). Area under the curve (AUC0-30) in the mechanically ventilated patients was 16.8 +/- 1.4 versus 23.4 +/- 1.9 ng/ml/puff x min in control subjects (p = 0.014). In summary, administration of albuterol with a MDI achieved a profile of serum levels in mechanically ventilated patients similar to that in healthy control subjects, but the peak serum level and systemic bioavailability (AUC0-30) were lower in the patients. In conclusion, serum levels reliably assess lower respiratory tract deposition of albuterol, and show that MDIs are more efficient for aerosol delivery in mechanically ventilated patients than was previously reported in studies using radiolabeled aerosols.

Aged↗
PubMed2001

[NO synthase activity in epitheliocytes of the rat bronchi following inhalation administration of adrenergic agonists and guanosine triphosphate].

NO synthase was studied in intact rats and in rats with bronchial asthma epitheliocytes after inhalation of phenotherol, propranolol, guanosine triphosphate (GTP) and combined inhalation of GTP with phenotherol. NO synthase mediator action on bronchial patency during adrenoagonists and GTP inhalation was demonstrated.

Administration, Inhalation↗
PubMedDate not supplied

Systemic genotoxic effects of tobacco-related nitrosamines following oral and inhalational administration to Sprague-Dawley rats.

An ex vivo model to detect nonspecific DNA damage in different rat tissues has been developed and employed to study systemic properties of tobacco-specific N-nitrosamines. One hour after treatment of rats with the carcinogens, primary, intact cells were isolated from various organs. Viability of the cells was monitored by trypan blue exclusion. Genotoxicity was determined by alkaline elution, in situ nick translation or microgel electrophoresis. We found that oral application of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces genotoxic effects in the liver (3.125-50 mg/kg), whereas N-nitrosonornicotine (NNN) is only moderately active (50-100 mg/kg). Furthermore, oral administration of NNK, NNN, and of N-nitrosodimethylamine (NDMA), induces DNA damage in the nasal cavity. In peripheral blood lymphocytes genotoxicity of NDMA (less than 2 mg/kg), but not of NNK (50 mg/kg), was observed. NDMA and NNK are just as genotoxic in the liver when administered by inhalation as orally (effective doses: 0.1-1 and 50 mg/kg, respectively). For human cancer, these results indicate that in addition to the susceptibilities in local organs (oral cavity after snuff dipping and lung after tobacco smoke inhalation), these nitrosamines also pose a risk systemically for more remote organs.

Administration, Inhalation↗
PubMed1998

Pharmacokinetic and pharmacodynamic evaluation of fluticasone propionate after inhaled administration.

OBJECTIVE: To evaluate the pharmacokinetic and systemic pharmacodynamic properties of inhaled fluticasone propionate (FP). METHODS: Single doses of 0.25, 0.5, 1.0 and 3.0 mg FP were administered to groups of six healthy subjects. Serum concentration profiles of FP were monitored over 24 h by means of high-performance liquid chromatography/mass spectrometry (HPLC/MS-MS). Systemic pharmacodynamic effects were evaluated by measuring endogenous serum cortisol and circulating white blood cells, and analyzed with previously developed integrated pharmacokinetic/pharmacodynamic (PK/PD) models. RESULTS: FP showed a dose-independent terminal half-life with a mean (SD) of 6.0 (0.7) h. Maximum serum concentrations occurred 1.0 (0.5) h after administration, ranging from 90 pg.ml(-1) for the 0.25 mg dose to 400 pg.ml(-1) for the 3.0 mg dose. This, together with an estimated mean absorption time of nearly 5 h and a known oral bioavailability of less than 1%, indicates prolonged residence at and slow absorption from the lungs. In the investigated dose range, the cumulative systemic effect was dose-dependent for both markers of pharmacodynamic activity. For doses of 0.25, 0.50, 1.0 and 3.0 mg FP, the PK/PD-based cumulative systemic-effect parameters were 159, 186, 257 and 372% .h for lymphocyte suppression, 107, 186, 202 and 348% .h for granulocyte induction and 23.6%, 33.8%, 51.0% and 73.6% for cortisol reduction, respectively. The time courses of lymphocytes, granulocytes and endogenous cortisol could be sufficiently characterized with the applied PK/PD models. The measured in vivo EC50 values, 30 pg.ml(-1) and 7.3 pg.ml(-1) for white blood cells and cortisol, respectively, were in good agreement with predictions based on the in vitro relative receptor affinity of FP. CONCLUSION: After inhalation, FP follows linear pharmacokinetics and exhibits dose-dependent systemic pharmacodynamic effects that can be described by PK/PD modeling.

Administration, Inhalation↗
PubMed1994

[The antiviral aerosol aprotinin. General effect on the body after inhalation administration].

A new medicine for the treatment of respiratory viral infections is described. It contains aprotinin, a natural inhibitor of proteases, and is used in the form of a fine aerosol for inhalation or intra-respiratory instillation. To estimate its innocuousness, the inhalation effect of the aerosol was studied on animals of two species. The experiments included examination of the functional state of the central nervous and cardiovascular systems, determination of the blood cell composition and biochemical blood count, morphological and histological investigation of the internal organs. The toxicological studies showed that aprotinin inhalation induced no adverse reactions which made it possible to recommend the aprotinin inhalation for the use in the treatment and prophylaxis of infections caused by a wide variety of respiratory viruses in humans.

Administration, Inhalation↗
PubMedDate not supplied

Inhalation administration of all-trans-retinoic acid for treatment of elastase-induced pulmonary emphysema in Fischer 344 rats.

A past study demonstrated that all-trans-retinoic acid (ATRA) treatment by intraperitoneal injection in a rat model of elastase-induced emphysema caused tissue regeneration as evidenced by a decrease in alveolar size and lung volume and an increase in alveolar number. We postulated that treatment with this retinoid by nose-only inhalation exposure would be a more efficient means of targeting damaged lung tissue. Emphysema was induced in male Fischer 344 rats by intratracheal instillation of pancreatic elastase (0.5 IU/g body weight). Four weeks after elastase instillation, animals were treated once daily, 4 days/week, for 3 weeks by exposing them nose-only to aerosolized ATRA (target concentration-time of 3000 or 15,000 mg-min/m3) or by injecting them intraperitoneally with ATRA in cottonseed oil (0.5 or 2.5 mg/kg). Based on estimates of particle deposition in the respiratory tract, inhalation doses were chosen to be consistent with injected doses. Lungs were fixed by inflation with formalin (constant pressure for 6 hours followed by >48 hours of immersion) and were embedded in paraffin. Sections were evaluated by histopathology and stereology. Inhalation exposure to ATRA at both aerosol concentrations caused significant elevations of ATRA in the lung, whereas only the high-dose injection treatment was associated with an elevation of lung ATRA. The mean ATRA concentration from lungs of rats in the high-dose inhalation exposure groups as measured by liquid chromatography--mass spectrometry was approximately 12-fold greater than that of high-dose injection-treated rats. Elastase instillation caused increased lung volumes, irregular alveolar air space enlargement, and fragmentation and attenuation of alveolar septa. Neither inhaled nor injected ATRA reduced the enlarged lung volumes associated with this emphysema model. Stereology demonstrated that alveolar air space enlargement in ATRA-treated rats was similar to that in sham-treated emphysematous animals. Thus, while inhalation treatment caused greater levels of the drug in lung tissue in comparison to that of injection-treated animals, treatment with ATRA by either route of administration did not cause a reversal of lung tissue damage in this model of elastase-induced emphysema.

Administration, Inhalation↗
PubMed1993

[Clinical trials of recombinant gamma-interferon. Circulating interferon and the 2,5-oligoadenylate synthetase activity after intramuscular and inhalation administrations].

It was shown that human recombinant gamma IFN given to volunteers intramuscularly (90 x 10(3) IU) and by inhalation (120 x 10(3) IU) induced 5-10-fold increase circulating IFN (up to 40-60 IU/ml); the activities of 2,5-oligoadenylate synthetase increased 1.5-2 fold and protein kinase of lymphocytes--3-5-fold. The repeated doses of gamma IFN at 12-15-hour intervals maintained a relatively stable IFN status, the inhalatory route of application being more effective. Convalescents after influenza different from healthy donors by a higher level of serum interferon and activity of 2.5-oligoadenylate synthetase but the activity of protein kinase was lowered in lymphocytes and plasma. The side effects induced by IFN administration were more marked only after intramuscular injections of 90 10 IU and were absent after inhalation of IFN (120,000 IU).

2',5'-Oligoadenylate Synthetase↗
PubMed1990

[Autoradiography study of organ distribution of 14C pentamidine following intravenous and inhalational administration in rats].

The organ distribution of 14C pentamidine was studied in Sprague Dawley rats by means of whole-body autoradiography following intravenous application and inhalation of aerosolized pentamidine. The distribution time after intravenous administration of 5 mg pentamidine per kg rat was 30 minutes, six hours, 24 hours, and seven days respectively. The corresponding times after administration of aerosolized pentamidine were 30 minutes and 24 hours. By measuring radioactivity in punch specimens of 100 microns sections, the distribution of radioactivity could also be determined semiquantitatively. Besides renal excretion, the excretion of pentamidine in the bile and via the salivary glands was assessed by autoradiography. Further target organs included the spleen and the bone marrow. As early as after 30 minutes no radioactivity was detectable in the blood vessels. A lack of radioactivity in the brain tissue, with concentration of pentamidine in the meninges, suggests that pentamidine does not pass the blood/brain barrier. Following intravenous administration, the lung uptake of pentamidine was relatively low. However, increased drug levels were recorded in the bronchial system. The elimination time of pentamidine from the target organs was long. The lung levels of pentamidine remained almost unchanged for a period of seven days. Following application by inhalation, high levels of pentamidine were measured in the lung. 14C pentamidine was also detectable in the oropharyngeal and gastrointestinal tract, the drug stemming from pentamidine ingested or licked off the skin by the animals. Other target organs could not be demonstrated. From the pharmacological point of view, these studies prove the advantages of pentamidine aerosol in the treatment of pneumocystis carinii pneumonia and provide information on extrarenal excretion mechanisms and deep compartments.

Administration, Inhalation↗
PubMed2003

In vivo efficacy in airway disease models of N-(3,5-dichloropyrid-4-yl)-[1-(4-fluorobenzyl)-5-hydroxy-indole-3-yl]-glyoxylic acid amide (AWD 12-281), a selective phosphodiesterase 4 inhibitor for inhaled administration.

N-(3,5-Dichloro-pyrid-4-yl)-[1-(4-fluorobenzyl)-5-hydroxy-indole-3-yl]-glyoxylic acid amide (AWD 12-281) is a highly potent and selective phosphodiesterase 4 (PDE4) inhibitor that was designed to have a metabolic profile that was optimized for topical administration. The aim of the current study was to explore the pharmacological profile of intratracheally administered AWD 12-281 in different models of asthma and chronic obstructive pulmonary disease (COPD) in comparison with steroids. To assess the anti-inflammatory potential of AWD 12-281, the antigen-induced cell infiltration in bronchoalveolar lavage fluid (BALF) of Brown Norway rats was determined. AWD 12-281 (ID50 of 7 microg/kg i.t.) as well as beclomethasone (0.1microg/kg i.t.) suppresses late-phase eosinophilia when administered intrapulmonary. Furthermore, AWD 12-281 has also strong anti-inflammatory properties when tested in lipopolysaccharide-induced acute lung neutrophilia in Lewis rats (ID50 of 0.02 microg/kg i.t.), ferrets (ID50 of 10 microg/kg i.t.), and domestic pigs (2-4 mg/pig i.t. or 1 mg/kg i.v.). In pigs, AWD 12-281 was as effective as beclomethasone (0.4 mg/pig i.t.) and dexamethasone (0.28 mg/kg i.v.), although at 3 to 10 times the dosage. The bronchodilatory activity of AWD 12-281 was assessed in sensitized guinea pigs. AWD 12-281 (1.5 mg/kg i.t., 1-h pretreatment) inhibited allergen-induced bronchoconstriction by 68% (parameter airway resistance). In sensitized BP-2 mice AWD 12-281 abolished the allergen-induced bronchial hyperresponsiveness and eosinophilia in BALF, showing dose dependence. When given orally, i.v. or i.t., AWD 12-281 has a considerably lower emetic potential than cilomilast in ferrets and roflumilast in pigs. When given topically by inhalation, no emesis could be induced in dogs up to the highest feasible dose (15 mg/kg in 50% lactose blend). These results indicate that AWD 12-281 is a unique potential new drug for the topical treatment of asthma and COPD.

3',5'-Cyclic-AMP Phosphodiesterases↗