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Biomedical subjects

M B Dolovich

Publications and source records attributed to M B Dolovich.

At least 19 recordsLinked to original sources
PubMed2003

Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications.

As the end organ for the treatment of local diseases or as the route of administration for systemic therapies, the lung is a very attractive target for drug delivery. It provides direct access to disease in the treatment of respiratory diseases, while providing an enormous surface area and a relatively low enzymatic, controlled environment for systemic absorption of medications. As a major port of entry, the lung has evolved to prevent the invasion of unwanted airborne particles from entering into the body. Airway geometry, humidity, mucociliary clearance and alveolar macrophages play a vital role in maintaining the sterility of the lung and consequently are barriers to the therapeutic effectiveness of inhaled medications. In addition, a drug's efficacy may be affected by where in the respiratory tract it is deposited, its delivered dose and the disease it may be trying to treat.

Absorption↗
PubMed2003

Pulmonary drug delivery. Part II: the role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications.

Research in the area of pulmonary drug delivery has gathered momentum in the last several years, with increased interest in using the lung as a means of delivering drugs systemically. Advances in device technology have led to the development of more efficient delivery systems capable of delivering larger doses and finer particles into the lung. As more efficient pulmonary delivery devices and sophisticated formulations become available, physicians and health professionals will have a choice of a wide variety of device and formulation combinations that will target specific cells or regions of the lung, avoid the lung's clearance mechanisms and be retained within the lung for longer periods. It is now recognized that it is not enough just to have inhalation therapy available for prescribing; physicians and other healthcare providers need a basic understanding of aerosol science, inhaled formulations, delivery devices, and bioequivalence of products to prescribe these therapies optimally.

Administration, Inhalation↗
PubMed2003

Uptake of 18fluorodeoxyglucose in the cystic fibrosis lung: a measure of lung inflammation?

Positron emission tomography is a three-dimensional imaging technique that measures physiological effects, including metabolism. 18Fluorodeoxyglucose has been extensively used as a tracer of cellular energy metabolism in the brain and in tumour detection. As neutrophils utilise glucose as an energy source during their respiratory burst, it was hypothesised that 18fluorodeoxyglucose uptake, by these cells, could be interpreted as a measure of neutrophil activation in cystic fibrosis (CF). Ten adult CF patients were given a bolus intravenous injection of 18fluorodeoxyglucose, followed by a 90-min dynamic mid-lung acquisition scan. Right-lung 18fluorodeoxyglucose uptake was assessed using a Patlak plot and values were converted to glucose utilisation. Three clinically inactive pulmonary sarcoidosis patients served as controls. From the 10 CF patients with baseline sputum neutrophils of 14 x 10(6) cells x mL(-1) who were investigated, seven were found to have sputum at a normal or slightly depressed glucose utilisation rate (mean 1.33 micromol x g(-1) x h(-1)) compared with a mean of 2.82 micromol x g(-1) x h(-1) for the sarcoidosis patients. In eight patients, receiving inhaled tobramycin therapy, no change in lung glucose utilisation or sputum neutrophil counts were found. Despite high-sputum neutrophil levels, lung glucose utilisation was not elevated in patients with cystic fibrosis.

Adult↗
PubMed2001

Aerosols and devices.

The success of aerosol therapy depends upon the delivery of ample amounts of the drug to appropriate sites in the lung with minimal side effects. Successful aerosol therapy delivery systems must provide sufficient respirable particles or droplets, with minimal loss of the drug. Ultimately, the patient must be able to use the device easily, maintain it, and derive clinical benefit from the drug delivered from the system.

Administration, Inhalation↗
PubMed2001

Measuring total and regional lung deposition using inhaled radiotracers.

The delivery of an inhaled drug to the lungs can be measured by adding a gamma-emitting radiotracer to the formulation and using two-dimensional planar imaging or three-dimensional single photon emission computerized tomography (SPECT) to provide detailed information on lung deposition. The isotope most commonly used is the low energy (140 KeV) isotope, 99m technetium. Radiolabeling techniques have been successfully developed for use with nebulizers, pressurized metered dose inhalers (pMDIs), and dry powder inhaler formulations (DPI), and to investigate drug delivery to the respiratory tract for a variety of drug formulations and patient populations. However, for pMDIs and DPIs, the radiotracer is usually only physically associated with, rather than chemically bound, to the drug. Therefore, once deposited, the radiotracer may disassociate from the drug and cannot be used to track its subsequent fate; however, incorporation of a radiotracer directly into the drug molecule can overcome this. By using positron emitters such as 11carbon or 18fluorine it is possible to generate three-dimensional images of the drug in the lung using positron emission tomography (PET) scanning, which has a higher resolution and is more accurate than SPECT. Labeling drugs with PET emitters is more complex as the drug molecule must first be synthesized to contain the radioactive isotope before the drug is formulated for the inhaler. As with gamma-scintigraphy, PET scanning can be used to investigate physiological changes in the lung following therapeutic intervention, but as biological radiotracers are used, functional images (i.e., of the drug's uptake and metabolism) can also be obtained.

Administration, Inhalation↗
PubMed1994

Optimization of a column liquid chromatographic procedure for the determination of plasma salbutamol concentration.

A reversed-phase column liquid chromatographic procedure with fluorescence detection for the determination of salbutamol in plasma is described. A l-ml aliquot of the sample, after the addition of bamethan as the internal standard, is passed through a Bond Elut silica extraction column. The column is selectively washed to remove neutral, acidic, and weakly basic compounds. The desired compounds are eluted with a l-ml aliquot of methanol. The eluate is evaporated under vacuum at ambient temperature and the residue is reconstituted in 40 microliters of the mobile phase which contains octanesulfonic acid as the ion-pairing reagent. The entire extract is injected onto a 150 x 4.6 mm I.D. column packed with 5-micron octylsilica particles. Peaks are detected with a fluorescence detector (excitation wavelength = 275 nm, emission wavelength = 310 nm). In the resulting chromatogram, salbutamol and the internal standard give sharp peaks that are well resolved from the extraneous peaks. The procedure allows the quantitation of salbutamol down to 0.2 ng/ml.

Albuterol↗
PubMed1994

Efficiency of bronchodilator aerosol delivery to the lungs from the metered dose inhaler in mechanically ventilated patients. A study comparing four different actuator devices.

STUDY OBJECTIVE: To compare aerosol delivery to the lungs in ventilated patients from two devices with holding chamber and two devices without holding chamber. DESIGN: A controlled clinical trial with randomization to one of four delivery devices. SETTING: An academic university-affiliated Canadian ICU. PATIENTS: Forty-eight patients undergoing mechanically assisted ventilation for a variety of clinical reasons and each judged to require inhaled bronchodilator therapy by the attending physician. INTERVENTIONS: Patients received 4 puffs of fenoterol labeled with technetium 99m pertechnetate delivered by metered-dose inhaler via 1 of the following: A, a 167-ml chamber device; B, a 700-ml chamber device; C, a nonchamber device (A, B, and C, all in the ventilator inspiratory line); and D, a nonchamber device on the end of the endotracheal tube. MEASUREMENTS AND RESULTS: One-minute images of the thorax were made by a portable gamma camera at the bedside. Deposition of radioactivity in the lungs (uncorrected for tissue absorption and calculated as a percentage of the radioactivity delivered from 4 puffs) was 5.53 +/- 0.72 (mean +/- 1 SEM), 6.33 +/- 1.16, 1.67 +/- 0.43, and 3.89 +/- 0.52 percent for devices A, B, C, and D, respectively (p = 0.004). Subgroup analysis showed a statistically significant difference in delivery between devices A and C and between devices B and C only. CONCLUSION: There were statistically significant differences between delivery from both chamber devices and the inline nonchamber device, but not between delivery from other devices. Further work will be necessary to determine the effect of device position in the ventilator circuit on aerosol delivery.

Aerosols↗
PubMed1994

Dose-effect relationship of the beta-agonists fenoterol and salbutamol in patients with asthma.

QUESTION: What is the relative per microgram potency and side effect profile of the beta-agonists salbutamol and fenoterol? METHOD: The relative bronchodilator (delta FEV1, V25, V50) potency and side effect profile (delta tremor, heart rate, breathlessness, BP) of nebulized salbutamol and fenoterol were evaluated by means of a randomized, double-blind, crossover, cumulative (50 to 2,500 micrograms) dose-response study. Both beta-agonists were administered to 12 patients with stable asthma over age 18 years with baseline FEV1 between 35 to 70 percent predicted. RESULTS: (1) Salbutamol and fenoterol both provided significant bronchodilatation compared with baseline. (2) There was no dose-effect difference between the two beta-agonists with respect to bronchodilator response. (3) Overall there was no significant difference between the side effect profiles of the two beta-agonists, although at the highest dose of fenoterol, there was marginally greater tremor when measured by accelerometry. (4) There was no difference in the vital signs or subjective patient evaluations of tremor, palpitations, or breathlessness as estimated by a visual analogue scale. (5) No significant adverse reactions occurred. SUMMARY AND CONCLUSION: Equivalent bronchodilatation and similar side effect profiles were measured in a group of patients with stable asthma after treatment with nebulized salbutamol or fenoterol in the dose range 50 to 1,250 micrograms (cumulative, 2,500 micrograms). This indicates that both beta-agonists have similar per microgram potency and side effect profiles. Observed clinical differences in response or side effects associated with fenoterol metered-dose inhaler administration may be a result of its higher dose per puff metered-dose inhaler formulation.

Administration, Inhalation↗
PubMed1992

Ciliary function, cell viability, and in vitro effect of ribavirin on nasal epithelial cells in acute rhinorrhea.

Nasal epithelial (NE) cells were collected from the nasopharynx of 25 individuals with symptomatic colds and 27 healthy volunteers (controls), and ciliary beat frequency (CBF) was assessed by microscopy employing video motion analysis techniques. Baseline CBF was statistically significantly elevated in the group with colds compared to the control group (14.6 +/- 1.5 Hz [mean +/- SD] vs 13.8 +/- 0.9 Hz; p = 0.02). After four days of incubation in culture, there was a significant decrease in the CBF in both groups, with a change from baseline of 1.9 Hz for the cold group, compared to 1.0 Hz for the control group (p = 0.0001). The in vitro addition of ribavirin at 500 micrograms/ml to NE cells from individuals with colds preserved the viability of the cells and maintained the CBF at baseline values. Twenty-four (96 percent) of 25 ribavirin-treated specimens from the cold group survived for four days in culture, compared with 17 (68 percent) of 25 untreated cold specimens. In addition, the ribavirin-treated cells had a mean CBF of 14.2 +/- 1.3 Hz, compared with 12.7 +/- 1.9 Hz for the untreated cell samples (p = 0.0005). Ribavirin had no effect on NE cells from the control group. These results suggest that ribavirin in a concentration of 500 micrograms/ml may have some benefit in the treatment of acute rhinorrhea.

Acute Disease↗
PubMed1990

Pressurized aerosol versus jet aerosol delivery to mechanically ventilated patients. Comparison of dose to the lungs.

The purpose of this study was to compare deposition of aerosol to the lung from a metered-dose inhaler (MDI) and aerosol holding chamber and from a jet nebulizer in ventilator-dependent patients. Twenty-one patients were entered into the study, all receiving assisted ventilation and inhaled bronchodilators because of airflow limitation. The average age was 68 yr; there were 10 men and 11 women. The patients were randomized to receive either 4 puffs (800 micrograms) of radiolabeled fenoterol by MDI of 1.75 ml (1,750 micrograms) of radiolabeled fenoterol solution by nebulizer. Imaging of lung fields was made by a portable scintillation camera at 5-min intervals during the study. Results showed that 20 patients completed the study, 9 receiving fenoterol by MDI, and 11 by jet nebulizer. Four were excluded from analysis because of previous pneumonectomy, two from each group. Lung deposition measured as a percent of given dose from either system was 5.65 +/- 1.09 (mean +/- SEM) for MDI plus extension chamber and 1.22 +/- 0.35 for jet nebulizer (p less than 0.001). Therefore, this trial shows significantly greater efficiency of aerosol deposition to the lung in ventilator-dependent patients when using an MDI plus aerosol holding chamber than when using a jet nebulizer.

Aerosols↗
PubMed1989

Reliable salbutamol administration in 6- to 36-month-old children by means of a metered dose inhaler and Aerochamber with mask.

A double-blind study was performed to demonstrate that bronchodilator can be administered reliably to infants and children under 3 years of age from a metered-dose inhaler (MDI) by means of an economical valved aerosol-holding chamber device (Aerochamber) fitted with a mask. Symptoms of cough and breathlessness were compared for two 1-week crossover periods with the child either taking active drug or placebo. The MDI and Aerochamber with mask is an effective delivery system for respiratory therapy in these young children.

Administration, Inhalation↗
PubMed1981

Standardization of inhalation provocation tests: influence of nebulizer output, particle size, and method of inhalation.

Standardization of inhalation tests requires a knowledge of factors that will affect the response. We measured the output and particle size of six types of nebulizers used for inhalation tests. Output varied considerably between nebulizers of different types (0.12 to 1.59 ml/min) and to a lesser extent between nebulizers of the same type. Particle size varied between 0.8 and 5.2 micrometer aerodynamic mass median diameter (AMMD). The influence of these two properties on bronchial response to inhaled methacholine was examined. Nebulizer output but not particle size (between 1.3 and 3.6 micrometer AMMD) altered the response. We also examined the effect of change in inspiratory time during inhalation from residual volume to total lung capacity on lung deposition of radiolabeled aerosol and on the provocative concentration of histamine required to reduce the 1-sec forced expiratory volume (FEV1) by 20% (PC20). A reduction in inspiratory time from 8 to 2 sec resulted in a lower total lung dose, relatively more aerosol deposited in central airways, and a higher PC20. The results emphasize the importance of keeping nebulizer output and pattern of breathing constant when performing inhalation provocation tests if consistent results are to be obtained.

Aerosols↗