Dose Inhaler Research Articles

Risk Factors Associated with Misuse of Soft Mist Inhaler in Patients with Chronic Obstructive Pulmonary Disease.

The use of inhaled bronchodilators is the mainstay of treatment for patients with chronic obstructive pulmonary disease (COPD). Although the soft mist inhaler (SMI) was developed to overcome the disadvantages of pressurized metered dose and drug powder inhalers, misuse during handling has been frequently observed in many studies. However, few studies have focused on SMI misuse among patients with COPD. Thus, we aimed to assess and identify the risk factors associated with SMI misuse among patients with COPD. In this prospective, observational, cross-sectional study, we enrolled patients with COPD who were undergoing SMI treatment between January 2018 and March 2020. An advanced nurse practitioner assessed the participants' handling of the device by using a check list. Among 159 participants, 136 (85.5%) reported inhaler misuse. Duration of COPD and COPD assessment test (CAT) scores were positively associated with inhaler misuse; adherence and education level were negatively associated with inhaler misuse. In the multivariable analysis, a low educational level (less than high school), high CAT score (≥ 10), and short duration of COPD (≤ 2 years) were identified as risk factors for SMI misuse. SMI misuse remains common among patients with COPD. Therefore, clinicians should pay close attention to their patients using SMIs, especially in the early period after the diagnosis of COPD.

Quality improvement project to improve inhaler delivery in the intensive care unit

Background Late 2022, an ICU nurse discovered that Seretide™ (salmeterol/Fluticasone) Evohaler, a commonly used inhaler, did not change its dose counter when used with the inhaler connector 22M-22F. This was identified as a medication safety issue. Knowledge gaps of inhaler use in mechanically ventilated patients were identified as well. Aims To effectively administer metered dose inhalers to ventilated patients and increase its accuracy and safety. Methods We instituted education programs for healthcare professional in the ICU and introduced a new inhaler connector RTC 24-V. This was compared with the existing 22M-22F connector in a comparative study. Results The dose counter of Seretide™ recorded prior to initiation and extubation showed an obvious drop in doses ranging from 15 to 63 in patients randomized to use RTC 24-V, compared to 0 to 2 drop in doses for patients using 22M-22F. A total of 51 pre study and 33 post study questionnaires were completed. Confidence that the accurate dose of medications was administered rose from 58.8% to 84.8% after using the RTC 24-V. Responses that there was no issue compromising patient safety rose from 0% to 51.5% and fewer staff expressed concern about disconnections causing infections, dropping from 51% to 9.1%. 93.9% of respondents chose the new RTC 24-V as the preferred inhaler connector. Conclusion The new inhaler connector RTC 24-V was assessed to have less medication errors. ICU healthcare professionals expressed greater confidence in its safety and accuracy. We will implement the use of this connector with continued medical education.

ФІКСОВАНА КОМБІНАЦІЯ ЕКСТРАМІЛКОДИСПЕРСНОГО БЕКЛОМЕТАЗОНУ ДИПРОПІОНАТУ ТА ФОРМОТЕРОЛУ — НОВІ МОЖЛИВОСТІ В ПОКРАЩЕННІ КОНТРОЛЮ АСТМИ

Despite the great work done in recent years on the dissemination and implementation of asthma recommendations, the level of control of the disease in the world and in Europe remains unsatisfactory in a significant percentage of patients. Factors associated with the treatment failure in patients with obstructive lung diseases are not only the low adherence to the prescribed drug therapy, incorrect use of the device (poor inhalation technique), insufficient communication between the physician and the patient, inadequate drug treatment. There are other factors associated with the disease: asthma and COPD are inflammatory disorders of the entire bronchial tree, including the peripheral airways. Their involvement may remain functionally and clinically silent until signs of air trapping and hyperinflation become apparent, resulting in a lack of symptom control despite conventional treatment. Inflammatory and functional changes in the small airways (<2 mm in diameter) contribute significantly to the pathogenesis of asthma in terms of bronchoconstriction and hyperreactivity. Today, the awareness of their role in the development of asthma is increasing and they are considered as a potential target for therapy aimed at achieving and maintaining optimal disease control. The determination of the role of the distal parts of the respiratory tract predicted the need for the development of a new generation inhalers that could generate aerosols with extra-fine particles of drugs for more effective penetration of the aerosol to the periphery of the lungs. The recent appearance of inhaled extra-fine particles inhaled drugs allows for a more uniform distribution of the active substance throughout the respiratory tract, including the peripheral airways. These drugs are more effective and require a lower nominal dose to achieve the same effect on lung function and symptoms compared to equipotent doses of non-extra-fine aerosols. Extra-fine fixed combination of beclomethasone dipropionate and formoterol 100/6 mcg (FOSTER) was the first registered metered dose inhaler for the MART regimen in asthma. Key words: asthma, distal airways, inhalers, asthma control, exacerbation.

Assessment of Inhaler Technique of Healthcare Workers in Port Harcourt, Nigeria

Introduction: Pressurized metered dose inhalers (pMDIs) are important in asthma management, however, their therapeutic effectiveness is dependent on correct use, as a poor technique would result in suboptimal drug delivery to the lungs. It is, therefore, necessary for healthcare professionals to know and teach proper pMDI techniques, to improve the outcomes in asthma management. Aim: The aim of the study was to assess pMDI technique instructions given by healthcare workers to patients with bronchial asthma. Method: This was a cross-sectional study done amongst healthcare workers who attended the 2022 World Asthma Day Workshop in Port Harcourt. An interviewer-administered questionnaire was used to obtain information on the demographic characteristics of participants. A model station was set up for the healthcare workers to give simulated health instructions to patients on the use of the provided pMDI. The correct identification of a pMDI and the stepwise pMDI training instructions of each participant were observed and scored according to the National Heart, Lung and Blood Institute protocol. Result: Sixty participants were recruited for the study.Ninety-eight per cent of the participants correctly identified a pMDI. However,88.3% gave less than 60% of the instructions required for proper demonstration of the inhaler technique. Conclusion: The study demonstrated poor pMDI technique among Health workers in Port Harcourt, Rivers State, Nigeria.

Understanding perspectives of asthma among pulmonologists in Indian settings: results from a questionnaire-based survey

Background: Asthma is associated with high morbidity and mortality in India. This survey was undertaken to explore the perspectives of pulmonologists towards in-clinic management of patients with asthma. Methods: It was a cross-sectional survey of pulmonologists conducted across India. It was formulated to provide unbiased observations of real-world clinical practice focusing on methods of diagnosis of asthma and its treatment preferences. Results: The participants included 805 pulmonologists, with the majority primarily treating patients with asthma (62%), chronic obstructive pulmonary disease (19%) and allergic rhinitis (19%). More than 86% of pulmonologists consider clinical symptoms, history of childhood asthma, family history, and chronic allergic rhinitis for initial diagnosis. About 19-23% prefer spirometry alone or in combination with family history for confirmation of asthma. The preferred inhaled corticosteroids-long-acting bronchodilator (ICS-LABA) combination was budesonide-formoterol amongst 83% of pulmonologists. For both dry powder inhaler (DPI) and metered dose inhaler (MDI) devices, fine particle fraction per cent and delivered dose were ranked as the two most important attributes. Conclusions: Asthma is the most prevalent diagnosis among patients treated by pulmonologists on the basis of clinical presentation and medical history. The most commonly used pharmacotherapy for the treatment of asthma comprises ICS-LABA, with budesonide-formoterol being the preferred combination. Fine particle fraction per cent and magnitude of delivered dose influence the choice of asthma inhaler prescriptions the most.

Rn-222 Activity Concentration and Age-Dependent Annual Effective Dose Analysis of Drinking Water Sources in Southern Benue State, Nigeria.

Radon is one of the carcinogenic radioactive gases causing radiological risk to the public via ingestion and inhalation. The 222Rn activity concentrations were estimated in potable water of Benue South (Otukpo and Ado Local Government Areas) using the Tri-Carb 1000 Liquid Scintillation Counter (LSC). 222Rn activity for Ado and Otukpo LGAS ranged from 2.281±1.861 to 27.525±1.861 Bq/L with a mean value of 10.031±1.861 Bq/L and 2.115±0.689 to 11.367±0.689 Bq/L with an arithmetic mean of 7.574±0.689 Bq/L respectively. The radon levels are within the reference level of 100 Bql−1 proposed by the WHO and EU Commission. Nearly 33% of the potable water had radon activity levels exceeding the maximum contamination level of 11.1 Bql−1 proposed by USEPA. The annual average ingestion dose values are lower than the action level of 100 µSvy−1 as proposed by the WHO and EU Commission. The values of dose variations of Annual effective dose (AED) to individuals were found to increase with age and water consumption rates. The estimated mean radio sensitivity for the different age groups followed a decreasing trend of Adults>Children>Infants in both Ado and Otukpo LGAs. The radiation dose for inhalation received by individual lungs from consumption of radon in water samples from Ado and Otukpo LGAs was significantly higher than the corresponding radiations received by the walls of the stomach. In conclusion, there is a possible occurrence of cancerous bronchial epithelium than stomach cancer over time in the study areas due to the consumption of water.

Удосконалення методології досліджень та оцінки інгаляційного та дермального впливу хімічних засобів захисту рослин. Частина ІІ.

Introduction. In the first part of the article, a comparative analysis of the domestic and international research methodology and assessment of the impact of plant protection products (PPP) on agricultural workers and the population is carried out. The analysis showed that the existing methodological approaches in Ukraine need to be improved. In particular, methodological approaches and procedures for their implementation should comply with international requirements for measuring external inhalation and dermal doses, calculating absorbed doses of the active substance (AS) PPP that affect persons subject to protection. Purpose of the Study. To develop procedures for studying and calculating the impact of the PPP on the operator, worker, outsider and resident during and after the application of the PPP that meet international requirements. Materials and Methods. A scientific analysis of domestic and foreign normative, methodological documents and scientific sources regulating the organization of research, measurement and calculation of the impact of PPP on agricultural workers and the population during and after the use of these products is carried out. Results. Based on the results of the analysis, procedures for sampling, delivery, storage of samples, description of data, calculation of exposure and absorbed doses of AS affecting the body of the operator, worker, outsider and resident by inhalation and dermal routes are proposed. Conclusions. The use of the proposed procedures will ensure that the studies comply with international requirements, and the results of their implementation will ensure the subsequent assessment and management of the PPP exposure risk to protected people. Keywords: plant protection products (PPP), inhalation and dermal exposure, operator, worker, outsider, resident, exposure and absorbed doses.

Radon activity and their radiological doses in drinking water of Chitradurga district, Karnataka, India.

In this investigation, radon activity concentration, inhalation and ingestion doses due to intake of radon in drinking water have been estimated in the Chitradurga district drinking water by using radon Emanometry technique. The average radon concentrations vary from 1.81±0.11 to 300.33±4.56Bql-1 with a mean value of 56.01±2.44Bql-1. Most of the radon concentration levels are within the World Health Organization (WHO) and European Union (EU) commission recommended level of 100Bql-1. About 70% of the drinking water had radon concentration level higher than the United States Environmental Protection Agency (USEPA) recommended Maximum Contamination Limit (MCL) of 11.1Bql-1. The annual ingestion dose varies from 0.38 to 63.03μSvy-1 with an average value of 11.75μSvy-1. The estimated annual ingestion dose is well within the WHO recommended reference level of 100μSvy-1.

PM1, PM2.5 and PM10 size fraction distribution under steady-state conditions in a walk-in type 222Rn calibration chamber facility.

Attachment of 222Rn progenies, upon their formation, to the atmospheric aerosols and inhalation of these radioactive aerosols causes inhalation dose to the human being. Aerosols have the characteristics of small particle size, long-time suspension and long-distance transmission and easy access to the deep respiratory tract. Aerosols are responsible for viral infection risk such as the recent worldwide pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, or COVID-19). Understanding the formation and behaviour of aerosols in a confined environment in various human habitations is essential to combat such detrimental exposures. Experiments have been performed to study the distribution of aerosol size fractions in the walk-in type 222Rn calibration chamber. The real-time applied particle technology monitors (APT-Maxima stationary monitors) were used for the simultaneous measurements of PM1, PM2.5, and PM10 size fractions. The variation of the mass densities (μgm-3) of different size fractions at different positions inside the chamber was monitored by placing APTs. The PM1, PM2.5, and PM10 sizes fractions were distributed homogeneously within the chamber volume and the concentration ratios of these fractions were 1:1.5:1.6 for concentration values of < 1500μgm-3, and 1:7:9 for the concentration values of > 1500μgm-3.

Cannabis vaporisation: Understanding products, devices and risks.

Vaporisation is a common method of cannabis administration. Inconsistent terminology and jargon regarding vaporisation has led to confusion. The increasing public interest and access to cannabis, combined with possible safety concerns associated with certain cannabis vaping products, warrants improved consumer and public and health care professional knowledge. To improve this knowledge, we conducted a review of the common terminology, regulatory status, products and device types related to cannabis vaporisation. Cannabis vaporisation devices can be separated into nine types. While vaporisation reduces respiratory risks associated with cannabis combustion, not all vaping products and device types carry the same level of safety. Metered dose inhalers and dried product vaporisers present the lowest safety risk due to a lower risk of toxin exposure and the use of lowertetrahydrocannabinol potency products. As both vaping and cannabis use increase in popularity, focusing on accurate health education will help facilitate health promotion to encourage lower risk use. The current lack of understanding on risk differences between types of cannabis vaporisation is a missed opportunity for harm reduction. Increased opportunities for public health and health care professional education on different cannabis vaporisation devices and associated risks are warranted. Improvements to health warning labelling may also be beneficial. Not all cannabis vaporisation devices and products carry the same level of risk. A better understanding of risk differentiation is needed among consumers and health professionals. Continued research, policy development and health education can lead to safer cannabis vaporisation.

Evaluation of outdoor radon levels and its dependence on the radium content in soil in the environs of Belagavi India

The paper presents the seasonal variation of outdoor radon levels and the measured lung dose to the population of the Belagavi region of India. The outdoor radon levels were measured in different seasons using LR-115 (type II) films fixed in a pin-hole cup detector. The outdoor radon levels in this work were found to be high in summer with values ranging from 11.8 to 27.3 Bq m−3 with a mean value of 20.0 Bq m−3. Lower radon levels were observed in monsoon season and the values range from 3.8 to 15.8 Bq m−3, with a mean value of 10.0 Bq m−3. The potential alpha energy concentration was maximum in summer with a mean value of 3.3 mWLM. The mean annual exposure was found to be 1.4 mWLM and the mean annual inhalation dose was 0.2 mSv y−1. The activity of 226Ra in soils was measured using a NaI (Tl) detector based on gamma ray spectrometer. The 226Ra activity of the study area was in the range of 16.5 to 70.4 Bq kg−1 with a mean value of 32.4 Bq kg−1. The correlation coefficient between the radium content in soil and outdoor radon levels was studied. The present study shows a significant correlation of 0.7, between outdoor radon levels and the radium content in the soil.

Simultaneous UPLC Assay for Oxitropium Bromide and Formoterol Fumarate Dihydrate in Pressurized Metered Dose Inhaler Products for Chronic Obstructive Pulmonary Disease.

Oxitropium bromide (OB) and formoterol fumarate dihydrate (FFD) are inhaler molecules that are widely used in the treatment of chronic lung diseases. The goal of this work was to create a reversed phase-ultra performance liquid chromatography (RP-UPLC) technique for assay and identification of OB and FFD, as well as identification and estimate of its associated compounds in pressurized metered dose inhaler product (pMDI). Separation of oxitropium and formoterol peaks were enhanced on a C18 (50 × 2.1 mm × 1.7 μm) UPLC column with ethylene-bridged-hybrid technology, The mobile phase consists of buffer (0.07 M KH2PO4) and acetonitrile (80:20, v/v). The detector wavelength of 210 nm, flow rate of pump 0.6 mL/min, and oven temperature for column were set at 25°C. The injection volume was 10 μL. The method run time was 2 min. The mobile phase was used as the solvent. Retention times (RTs) were 0.5 min for OB and 1.0 min for FFD. The assay analysis was linear range for all analytes within the range for concentrations 0.03-14.8 µg/mL of OB, 0.01-0.88 µg/mL of FFD. LOD values and LOQ values 0.009 and 0.026 µg/mL for OB and 0.003 and 0.009 µg/mL for FFD, respectively. Recoveries were obtained at 96.3% for OB and 97.2% for FFD. Precisions values were (as RSD, %) ≤1.5%. With the UPLC method developed and validated according to the current ICH guidelines, it is possible to simultaneously detect OB and FFD of assay analysis in pMDI products accurately, precisely and selectively, independent of the matrix effect. The present method is the first method in the literature based on the UPLC method for this purpose. The UPLC method is a time-saving method, it provides a faster and cheaper technique than the high performance liquid chromatography (HPLC) method.

Effect of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler combined with nasal high-flow nasal cannula on elderly patients with COPD and respiratory failure.

To explore the clinical effect of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) combined with high-flow nasal cannula (HFNC) in the treatment of elderly patients with chronic obstructive pulmonary disease (COPD) and respiratory failure. The clinical records of 94 elderly patients with COPD and respiratory failure who were treated in Yongkang First People's Hospital from February 2022 to January 2023 were retrospectively selected. Among them, 46 patients received HFNC alone (Control-group) and 48 patients received HFNC combined with BGF MDI (Study-group). The treatment effect, arterial blood gas status, pulmonary function, and acute physiology and chronic health evaluation (APACHE) II score before and after treatment were analyzed in both groups. The total efficacy of treatment in the Study-group (95.8%) was higher than that in the Control-group (78.3%) (P<0.05). After treatment, the partial pressure of arterial carbon dioxide (PaCO2), residual volume, and APACHE II scores in the two groups decreased compared to those before treatment, with the Study-group lower overall. However, arterial oxygen saturation (SaO2), oxygen partial pressure (PaO2), the percentage of peak expiratory flow (PEF), and forced expiratory volume in one second (FEV1) as percent of predicted (%FEV1) were higher than before treatment, and higher in the Study-group (P<0.05). Compared with HFNC alone, BGF MDI combined with HFNC can effectively regulate the arterial blood gas status of elderly patients with COPD and respiratory failure, restore pulmonary function, and improve the overall treatment effect.

Development of a Novel Bronchodilator Vaping Drug Delivery System Based on Thermal Degradation Properties.

This work aims to investigate bronchodilator delivery with the use of different vaping drug delivery systems (VDDS) by determining the dose equivalence delivered in relation to different references: a clinical jet nebulizer, a pMDI (pressurized metered dose inhaler) and a DPI (dry powder inhaler). Three different bronchodilators were used (terbutaline, salbutamol hemisulfate, ipratropium bromide). The e-liquids contained the active pharmaceutical ingredient (API) in powder form. Two different VDDS were tested (JUUL and a GS AIR 2 atomizer paired with a variable lithium-ion battery (i-stick TC 40 W), 1.5 ohm resistance, and 15 W power). Samples were collected using a glass twin impinger (GTI). High-performance liquid chromatography (HPLC) was used to quantify the drugs. A next-generation impactor (NGI) was used to measure the particle size distribution. Terbutaline emerged as the optimal API for bronchodilator delivery in both VDDS devices. It achieved the delivery of a respirable dose of 20.05 ± 4.2 µg/puff for GS AIR 2 and 2.98 ± 0.52 µg/puff for JUUL. With these delivered doses, it is possible to achieve a dose equivalence similar to that of a jet nebulizer and DPI, all while maintaining a reasonable duration, particularly with the GS AIR 2. This study is the first to provide evidence that vaping bronchodilators work only with appropriate formulation, vaping technology, and specific drugs, depending on their thermal degradation properties.

Effect of experimental therapy on the gas and acid–base composition of the blood in the dynamics of toxic pulmonary edema

BACKGROUND: This study is part of an extended research onfinding ways to prevent and treat toxic pulmonary edema. This study aimed to examine the gas transport function, acid–base state, and gas composition of blood in the dynamics of experimental toxic pulmonary edema and the effect on them of experimental therapy with a combination of drugs that have shown effectiveness in preliminary studies.&#x0D; MATERIALS AND METHODS: Toxic edema of the lungs was modeled in mice by inhalation of toxic doses of phosgene LСt50. Gas and acid–base composition parameters of the blood were determined using a gas analyzer 3 and 24 h after poisoning. Thirty minutes after poisoning, parts of the animals were injected intraperitoneally with a complex of drugs consisting of natrii dimercaptopropansulfonas (unitiol) 150 mg/kg, diclofenac sodium 35. 0 mg/kg, and аprotinin (contrikal) 250 IU/kg.&#x0D; RESULTS: The results revealed 3 h after poisoning of animals, changes in the gas composition and parameters of the gas transport function in the blood were detected, and 24 h after poisoning, impaired acid-base balance was noted. The use of a therapeutic combination of drugs consisting of sodium dimercaptopropanesulfonate (unithiol), sodium diclofenac, and aprotinin (kontrikal) led to the partial normalization of the altered parameters of the blood gas composition and parameters of the blood gas transport function but was not accompanied by the normalization of the acid-base state of the blood. The formulation demonstrated a pronounced negative effect on the blood gas composition in intact animals. The treatment of pulmonary edema with the comparison drug unithiol did not result in the normalization of the gas composition and acid-base state of the poisoned animals.&#x0D; CONCLUSION:The treatment of toxic pulmonary edema with a combination of medications led to an improvement in the gas composition and gas transport function of the blood.

Dose and gender dependence of chlorine inhalation in a conscious ovine model

Characterization of the pathophysiology of ARDS following chlorine gas inhalation in clinically relevant translational large animal models is essential, as the opportunity for clinical trials in this type of trauma is extremely limited. To investigate Cl2 concentration and gender-dependent ARDS severity. Sheep (n = 54) were exposed to air or Cl2 premixed in air at a concentration of 50, 100, 200, and 300 ppm for 30 min under anesthesia/analgesia and monitored for an additional 48 h in a conscious state. Cardiopulmonary variables and survival endpoints were compared between male and female sheep. Overall there were no significant differences in the responses of female and male sheep except pulmonary oxygenation tended to be better in the male sheep (300 ppm group), and the pulmonary arterial pressure was lower (200 ppm group). The onset of mild ARDS (200 < PaO2/FiO2 ≤ 300) was observed at 36 h post exposure in the 50 ppm group, whereas the 100 ppm group developed mild and moderate (100 ≤ PaO2/FiO2 ≤ 200) ARDS by 12 and 36 h after injury, respectively. The 200 ppm and 300 ppm groups developed moderate ARDS within 6 and 3 h after injury, respectively. The 300 ppm group progressed to severe (PaO2/FiO2 ≤ 100) ARDS at 18 h after injury. Increases in pPeak and pPlateau were noted in all injured animals. Compared to sham, inhalation of 200 ppm and 300 ppm Cl2 significantly increased lung extravascular water content. The thoracic cavity fluid accumulation dose-dependently increased with the severity of trauma as compared to sham. At necropsy, the lungs were red, heavy, solidified, and fluid filled; the injury severity grew with increasing Cl2 concentration. The severity of ARDS and mortality rate directly correlated to inhaled Cl2 concentrations. No significant sex-dependent differences were found in measured endpoint variables.

Behavioral and Pharmacokinetic Assessment of Nicotine e-Cigarette Inhalation in Female Rats.

Nicotine and tobacco use remain high both globally and in the United States, contributing to large health care expenditures. With a rise in e-cigarette use, it is important to have clinically relevant models of inhaled nicotine exposure. This study aims to extend prior preclinical nicotine inhalation animal data to females and provide both behavior and serum pharmacokinetics. We tested two inhalation doses of nicotine (24 mg/mL and 59 mg/ mL) and compared these to injected doses (0.4 mg/kg and 1 mg/kg). In addition, we assessed locomotor behavior after the same doses. Blood was collected at 10- and 120-minutes post-administration. We assessed nicotine and cotinine serum concentrations by LC-MS/MS. Showed that while nicotine serum concentrations for the respective high and low-dose administrations were similar between both routes of administration, the route had differential effects on locomotor behavior. Inhaled nicotine showed a dose-dependent decrease in locomotor activity while injected doses showed the opposite trend. Our results indicate that the route of administration is an important factor when establishing preclinical models of nicotine exposures. Given that the overall use of e-cigarettes in vulnerable populations is on the rise, our study provides important behavioral and pharmacokinetic information to advance our currently limited understanding of the effects of nicotine vapor exposure. This study highlights behavioral differences between different routes of administration of similar doses of nicotine. Using a low and high dose of nicotine, we found that nicotine serum concentrations were similar between the different routes of administration. Our results indicate that different routes of administration have opposing effects on locomotor activity. These findings provide important implications for future behavioral models.

The Pharmacokinetics of CPZEN-45, a Novel Anti-Tuberculosis Drug, in Guinea Pigs.

CPZEN-45 is a novel compound with activity against drug-susceptible and drug-resistant tuberculosis (TB). The present study was undertaken to determine the best dose and dosing regimen of inhalable CPZEN-45 powders to use in efficacy studies with TB-infected guinea pigs. The disposition of CPZEN-45 after intravenous, subcutaneous (SC), and direct pulmonary administration (INS) was first determined to obtain their basal pharmacokinetic (PK) parameters. Then, the disposition of CPZEN-45 powders after passive inhalation using consecutive and sequential doses was evaluated. Plasma concentration versus time curves and PK parameters indicated that the absorption of CPZEN-45 after INS was faster than after SC administration (Ka = 12.94 ± 5.66 h-1 and 1.23 ± 0.55 h-1, respectively), had a longer half-life (2.06 ± 1.01 h versus 0.76 ± 0.22 h) and had higher bioavailability (67.78% and 47.73%, respectively). The plasma concentration versus time profiles and the lung tissue concentration at the end of the study period were not proportional to the dose size after one, two, and three consecutive passive inhalation doses. Three sequential passive inhalation doses maintained therapeutic concentration levels in plasma and lung tissue for a longer time than three consecutive doses (10 h vs. 3 h, respectively). Future studies to evaluate the efficacy of inhaled CPZEN-45 powders should employ sequential doses of the powder, with one nominal dose administered to animals three times per day.

Does mixing inhaler devices lead to unchecked inhaler technique errors in patients with COPD? Findings from the cross-sectional observational MISMATCH study

BackgroundPatients with chronic obstructive pulmonary disease (COPD) may be prescribed multiple inhalers that require different techniques for optimal performance. Mixing devices has been associated with poorer COPD outcomes suggesting that...

Estimation of Radon/Thoron and their progeny concentration in some dwellings and exhalation rates from soils of Samana city, Patiala

The study of indoor pollutants and radioactive nuclides imposes importance on human health as we spend most of our time indoors. Out of all the natural radioactive elements, Radon-222 and Radon220 are present in large abundance indoors. Both are radioactive and decay to various short-lived progenies by emitting high-energy alpha particles, so inhalation of such gases can harm the human body in various ways. In the present report, the concentration of Rn-222 and Rn-220 and its progenies are estimated from some dwellings of Samana city of Patiala district, Punjab. Pin-hole dosimeters with DRPS and DTPS were employed in 15 houses in the study area to measure indoor Rn-222 and Rn-220 concentrations. The concentration of Rn-222 ranges between 401.96 Bq/m3 and 27.36 Bq/m3 with mean value of 138.82 Bq/m3, and the concentration of Rn-220 varies from 222.2 Bq/ m3 to 50 Bq/m3 with the mean weight of 131.12 Bq/m3. The average inhalation dose was also calculated from the results and was found to have an average value of 2.19 mSv per year. The average weight of radon concentration was below the ICRP recommendation of 200-300 Bq/m3 but the value is above these limits at some locations. Radon and thoron emission rates from soil samples near to the dwellings was also calculated.