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PubMed1997

Human tumor blood flow is enhanced by nicotinamide and carbogen breathing.

Perfusion insufficiency and the resultant hypoxia are recognized as important mechanisms of resistance to anticancer therapy. Modification of the tumor microenvironment to increase perfusion and oxygenation of tumors may improve on the efficacy of these treatments. Using laser Doppler probes to measure microregional RBC flux, this study examines the influence of nicotinamide and carbogen on human tumor perfusion. Ten patients with advanced cancers were studied. Nicotinamide (80 mg/kg) was given p.o., and 60 min later, up to six probes were inserted into the tumor. Readings were taken for 1 h, followed by 10 min of carbogen breathing and 10 additional min of breathing room air. Results were compared with those from a similar group of eight control patients who were not given nicotinamide, but who breathed carbogen. In 44 microregions analyzed, 33 (73%) showed perfusion fluctuations of 50% or more, and 20 (44%) by 100% or more. This compared with the control group in whom 62% and 27% of microregions varied by 50% or more and 100% or more, respectively. Perfusion increases outweighed decreases by 30% with nicotinamide and 20% in the controls. On breathing carbogen, patients pretreated with nicotinamide showed an increase in tumor perfusion of 17% at 5 min and 22% at 10 min, compared with only 0% and 1% in the control group. Pretreatment with nicotinamide made little difference to the random blood flow fluctuations seen in controls. However, when carbogen was introduced, tumor perfusion increased compared with the control group. This may have important therapeutic implications by improving response to treatment and allowing better delivery of systemically administered agents.

Administration, Inhalation↗
PubMed1998

Drug trials.

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Administration, Inhalation↗
PubMed1998

[Comparative efficacy, safety, cardio-hemodynamic effects of isosorbide dinitrate (ID) aerosol and sublingual tablets of nitroglycerin].

AIM: To study efficacy, safety, cardiohemodynamic effects of ID aerosol--isoket--for relief of anginal attacks and their prevention in long-term treatment. MATERIALS AND METHODS: 15 patients with ischemic heart disease suffering from stable angina class II-III. Isoket was tried for efficacy, tolerance, hemodynamic parameters, morphofunctional status of the heart, exercise tolerance. RESULTS: Isoket aerosol in a dose 1.25 mg as a single oral spray arrested anginal attacks in all the patients. In long-term regimens good antianginal effect was achieved in 60% of cases. The ID aerosol produces a fast antianginal effect, improves morphofunctional cardiac parameters and exercise tolerance. CONCLUSION: Isoket spray is effective and safe antianginal drug.

Administration, Inhalation↗
PubMed1998

Antibody response of cattle experimentally inoculated with parainfluenza type-3 live vaccine in a post-tracheal position.

One of the major viral respiratory diseases of cattle is parainfluenza type-3 virus infection. Attenuated live virus vaccines have been used in most countries. An experimental attempt was made to clarify the antibody response of cattle inoculated with a live vaccine in a post-tracheal position by a spray method. A significantly higher titers of antibodies in both hemagglutination inhibition and neutralization were obtained in the serum samples of animals vaccinated in this manner than those vaccinated by intramuscular injection or intranasal instillation.

Administration, Inhalation↗
PubMed1999

Drugs for asthma.

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Acetates↗
PubMed1997

Dependency of cortisol suppression on the administration time of inhaled corticosteroids.

Endogenous cortisol suppression is one of the major systemic side effects of inhaled corticosteroids in the treatment of asthma. A previously developed pharmacokinetic/ pharmacodynamic approach was used to evaluate the influence of administration time on the cumulative cortisol suppression (CCS) after single doses of the inhaled corticosteroids flunisolide and fluticasone propionate. Administration time-dependent simulations of CCS were performed with drug-specific pharmacokinetic and pharmacodynamic parameters obtained from previous clinical trials. Both drugs showed similar diurnal variation in CCS, dependent on the administration time, with maximum suppression when administered in the early morning at approximately 3 AM. The optimum administration time for minimized CCS was in the afternoon but was shifted from 3 PM for fluticasone propionate to later time points around 7 PM for flunisolide, probably because of the shorter terminal elimination half-life of flunisolide. Regarding peak to trough fluctuation, however, CCS after fluticasone propionate showed only half the administration time dependency as after flunisolide. Therefore, the ratio between CCS after flunisolide and after fluticasone propionate also followed administration time-dependent variations. This led to the conclusion that administration time has to be considered as a pivotal influential factor in clinical studies comparing CCS among different inhaled corticosteroids.

Administration, Inhalation↗
PubMed1987

Protection by parenteral iron administration against the inhalation toxicity of beryllium sulfate.

Animals exposed to an aerosol of BeSO4 showed a significant reduction in mortality with iron treatment. Rats were exposed for 2 h in a nose-only inhalation chamber for 14 days to an aerosol of 2.59 micrograms/Be/l. The cumulative mortality of animals concurrently treated with iron salt was significantly reduced (P less than 0.05) compared to animals which had not received iron treatment.

Administration, Inhalation↗
PubMed1993

Plasma concentrations in methyl isobutyl ketone-potentiated experimental cholestasis after inhalation or oral administration.

In studies of methyl isobutyl ketone (MiBK)-potentiated cholestasis induced by taurolithocholic acid (TLC) or manganese-bilirubin (Mn-BR) combinations, MiBK is usually given by gavage whereas industrial exposure to MiBK normally occurs by inhalation. The present study was conducted to verify if the route of administration could influence the potentiation. Male Sprague-Dawley rats were treated with MiBK for 3 days orally or by inhalation (4 hr/day). The minimal effective doses (MED) for potentiating both models of intrahepatic induced cholestasis were estimated to be 3 mmol/kg or 400 ppm for the oral or inhalation route, respectively. Groups of rats were treated with 0.5, 1, or 2 times the MED. Half of each group was sacrificed after the last MiBK administration to determine plasma concentrations of MiBK and its metabolites by gas-liquid chromatography. The other half was challenged 18 hr later with TLC (30 mumol/kg) or a combination of manganese (4.5 mg/kg) and bilirubin (15 mg/kg). Bile flow was measured from 15 to 135 min after the cholestatic challenge. Rats exposed to MiBK orally or by inhalation exhibited an enhanced diminution in bile flow that was dose-dependent. With dosages of 3 mmol/kg po or 400 ppm by inhalation or more, diminution in bile flow was significantly different from control values. Comparisons between maximal bile flow decrease and MiBK plasma concentration showed that the severity of the hepatotoxic response was dependent on the plasma MiBK concentration, irrespective of the route of administration.

Administration, Inhalation↗
PubMed1997

Inhaled nitric oxide in acute respiratory distress syndrome.

BACKGROUND: Inhaled nitric oxide has been shown to improve oxygenation in select patients with acute respiratory distress syndrome (ARDS). OBJECTIVE: The purpose of this study was to evaluate the clinical response to four concentrations of inhaled nitric oxide (NO) in 20 patients with ARDS. METHODS: All patients with ARDS were eligible for the study. ARDS was defined as (1) the presence of a predisposing factor; (2) a PaO2/FiO2 ratio < 200; (3) bilateral infiltrates on chest radiograph; and (4) absence of evidence of congestive heart failure and pulmonary artery wedge pressure < 18 mm Hg. Patients received each of four doses (1, 15, 30, and 60 ppm) in random order, each for a 3-hour period. Cardiovascular variables were continuously monitored, and arterial and mixed venous blood gas measurements were obtained at 30 minutes and 3 hours. RESULTS: Thirteen of the 20 patients demonstrated a significant increase in their PaO2/FiO2 (> 20% increase) when treated with inhaled NO. The administration of inhaled NO was associated with an increase in oxygenation at doses of 1, 15, and 30 ppm, but not 60 ppm. Increasing NO dose to more than 1 ppm did not significantly improve response. Mean pulmonary artery pressure decreased with increasing NO concentration, but this did not reach statistical significance. Nine of the 13 responding patients and 2 of the 7 nonresponding patients survived. CONCLUSION: Inhaled NO was successful in increasing PaO2/FiO2 by > 20% in 65% of the surgical patients in this trial. Response to NO could not be predicted by initial PaO2/FiO2 or pulmonary artery pressures. A trial of inhaled NO at a dose of < 10 ppm may be helpful in ARDS patients requiring increasing FiO2 and positive end-expiratory pressure.

Administration, Inhalation↗
PubMed2006

Non-comparative evaluation of the safety of aerosolized amphotericin B lipid complex in patients undergoing allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplant (HSCT) recipients are at increased risk for invasive fungal infections (IFIs) over prolonged periods of time. Aerosolized amphotericin B lipid complex (ABLC) has shown promise in lung transplant recipients as a convenient means of delivering protective drug to the upper airways avoiding systemic toxicities. The safety and tolerability of aerosolized ABLC in 40 subjects undergoing allogeneic HSCT was prospectively investigated in an open-labeled, non-comparative study. Subjects received aerosolized ABLC treatment once daily for 4 days, then once weekly for 13 weeks; fluconazole was administered daily as standard of care through post-transplant day 100. Pulmonary mechanics were measured before and after each dose of inhaled ABLC; adverse events (AEs) and the development of IFI were also monitored. Cough, nausea, taste disturbance, or vomiting followed 2.2% of 458 total inhaled ABLC administrations; 5.2% of inhaled ABLC administrations were associated with >or=20% decrease in pulmonary function measurements (forced expiratory volume in 1 second or forced vital capacity) and none required treatment with bronchodilators or withdrawal from study. Four mild AEs were considered possibly or probably related to study treatment; no deaths or withdrawals from treatment were attributed to study drug. Of 3 proven IFIs occurring during the study period, only 1, a catheter-related case of disseminated fusariosis, occurred while the subject was receiving study medication. Aerosolized ABLC was well tolerated in allogeneic HSCT recipients. With only 1 of 40 subjects developing IFI while receiving treatment, the combination of fluconazole and inhaled ABLC warrants further study as antifungal prophylaxis following allogeneic HSCT.

Adolescent↗
PubMed1990

Increased biopterin production in rats with tumors induced by radon inhalation and benzonaphthoflavone administration.

Serial determinations of urinary biopterin were performed in rats during the development of lung tumors induced by radon inhalation and 5,6-benzonaphtoflavone administration. A striking increase in biopterin levels was observed in animals which developed single or multiple epidermoid carcinoma of the lung and this increase occurred several weeks before tumors could be detected radiographically.

Animals↗
PubMed1992

Trials of the bronchodilator activity of the isoenzyme-selective phosphodiesterase inhibitor AH 21-132 in healthy volunteers during a methacholine challenge test.

1. An approximately steady-state reduction of specific airway conductance was induced in normal human subjects by means of a methacholine individualized loading+maintenance dose regime. Tested against this background bronchoconstriction, the mixed type III/IV phosphodiesterase inhibitor AH 21-132, ingested in doses up to 90 mg, had no detectable bronchodilator activity. 2. AH 21-132, infused intravenously over 15 min, evoked short-lived bronchodilatation at doses of 20 and 40 mg, without affecting blood pressure or heart rate. 3. AH 21-132, mixed 1:18.5 by weight with sucrose, dissolved in saline, nebulized and inhaled in doses between 2 and 24 mg of AH 21-132, produced dose-dependent bronchodilation. The ED50 was estimated as 9.2 mg AH 21-132. The peak relief of imposed bronchoconstriction was 80% and the apparent half-time of removal of AH 21-132 from its site of action was 25 min. 4. Inhaled, nebulized, hypertonic sucrose had a minor bronchodilator action. 5. AH 21-132, by intravenous and inhaled routes of administration, provides relief of methacholine-induced bronchoconstriction.

Administration, Inhalation↗