Oral sedatives.
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Administration, Inhalation↗
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Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
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Emerging technologies that overcome biological barriers for therapeutic protein delivery.
In the past decade, genomic research and the nascent field of proteomics have exponentially increased the number of potential protein therapeutic molecules for treating medical needs that were previously unmet. To realise the full clinical potential of many of the novel protein drug entities arising from these intense research efforts, emerging protein delivery technologies may be required. Advanced delivery technologies may offer the ability to overcome biochemical and anatomical barriers to protein drug transport, without incurring adverse events, to deliver the agent(s) at a certain desired rate and duration, to protect therapeutic macromolecules from in situ or systemic degradation, as well as increase their therapeutic index by targeting the drug action to a specific site. This review will cover a myriad of novel and emerging technologies that are directed at bypassing biological barriers and that have shown promise in advancing the therapeutic potential of protein drugs.
Administration, Cutaneous↗
Cyclodextrins in drug delivery.
Cyclodextrins are a family of cyclic oligosaccharides with a hydrophilic outer surface and a lipophilic central cavity. Cyclodextrin molecules are relatively large with a number of hydrogen donors and acceptors and, thus, in general they do not permeate lipophilic membranes. In the pharmaceutical industry cyclodextrins have mainly been used as complexing agents to increase aqueous solubility of poorly soluble drugs, and to increase their bioavailability and stability. Studies in both humans and animals have shown that cyclodextrins can be used to improve drug delivery from almost any type of drug formulation. However, the addition of cyclodextrins to existing formulations without further optimisation will seldom result in acceptable outcome. Currently there are approximately 30 different pharmaceutical products worldwide containing drug/cyclodextrin complexes on the market.
Administration, Cutaneous↗
Alternative administration of camptothecin analogues.
In order to improve the therapeutic index of camptothecin (CPT) analogues, alternative administration of CPT analogues is being evaluated. Topotecan, irinotecan, rubitecan, lurtotecan and 9-aminocamptothecin have been administered orally with response rates equivalent to that seen after intravenous administration, where applicable. Oral availability and administration of some of the newer CPT analogues, including diflomotecan (BN80915) and grimatecan (ST1481), have also shown promising results. Aerosolisation of liposomal 9-nitrocamptothecin has been studied in patients with advanced malignancies involving the lung, demonstrating systemic antitumour activity. Intrathecal administration of topotecan has been studied in children with refractory neoplastic meningitis. It is well tolerated and associated with some antitumour activity. Intraperitoneal administration of topotecan as consolidation therapy in patients with ovarian cancer has shown promising results. Transdermal administration of rubitecan has been studied in mice. So far, no CPT has been approved for an alternative route of administration.
Administration, Cutaneous↗
Noninvasive delivery technologies: respiratory delivery of vaccines.
This paper reviews the developments in noninvasive methods of drug delivery, with a focus on the delivery of vaccines via the respiratory tract. Recent results indicate that the respiratory system, and the nasal mucosa in particular, provide a valuable target site for immunisation against respiratory and mucosal pathogens. Vaccine delivery via the nasal and pulmonary routes each present distinct sets of performance requirements. Current delivery systems in development for both routes are reviewed herein. The storage and respiratory delivery of drugs and vaccines in powder form has been shown to provide improved stability and extended retention time in the respiratory mucosa. These features, in addition to the noninvasive nature of respiratory delivery, can provide benefits to public health vaccination campaigns, facilitating mass vaccination without the high cost of maintaining cold-chain storage.
Administration, Inhalation↗
Alternative routes of drug administration--advantages and disadvantages (subject review). American Academy of Pediatrics. Committee on Drugs.
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Administration, Cutaneous↗
Ipratropium bromide added to asthma treatment in the pediatric emergency department.
OBJECTIVE: To determine if the addition of ipratropium bromide to the emergency department (ED) treatment of childhood asthma reduces time to discharge, number of nebulizer treatments before discharge, and the rate of hospitalization. METHODS: Patients >12 months of age were eligible if they were to be treated according to a standardized ED protocol for acute asthma with nebulized albuterol (2.5 mg/dose if weight <30 kg, otherwise 5 mg/dose) and oral prednisone or prednisolone (2 mg/kg up to 80 mg). Subjects were randomized to receive either ipratropium (250 microg/dose) or normal saline (1 mL/dose) with each of the first three nebulized albuterol doses. Further treatment after the first hour was determined by physicians blinded to subject group assignment. Records were reviewed to determine the length of time to discharge home from the ED, number of doses of albuterol given before discharge, and the number of patients admitted to the hospital. RESULTS: Four hundred twenty-seven patients were randomized to ipratropium or control groups; these groups were similar in all baseline measures. Among patients discharged from the ED, ipratropium group subjects had 13% shorter treatment time (mean, 185 minutes, vs control, 213 minutes) and fewer total albuterol doses (median, three, vs control, four). Admission rates did not differ significantly (18%, vs control, 22%). CONCLUSIONS: The addition of three doses of ipratropium to an ED treatment protocol for acute asthma was associated with reductions in duration and amount of treatment before discharge.
Administration, Inhalation↗
Pharmacoeconomic studies of asthma controller drugs: marketing gimmick or icing on the cake?
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Acetates↗
Patterns of tooth wear associated with methamphetamine use.
BACKGROUND: Methamphetamine (MAP) abuse is a significant worldwide problem. This prospective study was conducted to determine if MAP users had distinct patterns of tooth wear. METHODS: Methamphetamine users were identified and interviewed about their duration and preferred route of MAP use. Study participants were interviewed in the emergency department of a large urban university hospital serving a geographic area with a high rate of illicit MAP production and consumption. Tooth wear was documented for each study participant and scored using a previously validated index and demographic information was obtained using a questionnaire. RESULTS: Forty-three MAP patients were interviewed. Preferred route of administration was injection (37%) followed by snorting (33%). Patients who preferentially snorted MAP had significantly higher tooth wear in the anterior maxillary teeth than patients who injected, smoked, or ingested MAP (P = 0.005). CONCLUSION: Patients who use MAP have distinct patterns of wear based on route of administration. This difference may be explained anatomically.
Administration, Inhalation↗
Clinical pharmacokinetics of amantadine hydrochloride.
Amantadine is a drug with diverse uses ranging from prevention of influenza A illness to the treatment of patients with Parkinson's disease. It is available only in oral formulations from which it is well absorbed and widely distributed, little drug being present in the circulation. Apparent volume of distribution is inversely related to dose over the therapeutic range and accounts in part for a noteworthy logarithmic increase in plasma concentration as a function of dose. Elimination is primarily by renal clearance by both glomerular filtration and tubular secretion. Amantadine accumulates in patients with renal dysfunction. Hence, doses must be reduced in such patients to avoid toxicity. Interactions with other drugs appear uncommon. Relationships have been demonstrated between amantadine therapeutic effects and plasma concentrations in different study cohorts, but not in individual patients. Dose schedules have been suggested for individuals in whom amantadine kinetics are different from healthy subjects. However, these schedules are controversial in their choice of target concentrations and in being untested as to predictive value.
Administration, Inhalation↗
Intranasal corticosteroids for allergic rhinitis: superior relief?
Whether first-line pharmacological treatment of allergic rhinitis should be antihistamines or intranasal corticosteroids has been discussed for several years. First-generation antihistamines are rarely used in the treatment of allergic rhinitis, mainly because of sedative and anticholinergic adverse effects. On the basis of clinical evidence of efficacy, no second-generation antihistamine seems preferable to another. Similarly, comparisons of topical and oral antihistamines have been unable to demonstrate superior efficacy for one method of administration over the other. Current data documents no striking differences in efficacy and safety parameters between intranasal corticosteroids. When the efficacy of antihistamines and intranasal corticosteroids are compared in patients with allergic rhinitis, present data favours intranasal corticosteroids. Interestingly, data do not show antihistamines as superior for the treatment of conjunctivitis. Safety data from comparative studies in patients with allergic rhinitis do not indicate differences between antihistamines and intranasal corticosteroids. Combining antihistamines and intranasal corticosteroids in the treatment of allergic rhinitis does not provide any additional effect to intranasal corticosteroids alone. On the basis of current data, intranasal corticosteroids seem to offer superior relief in allergic rhinitis than antihistamines.
Administration, Inhalation↗
The role of corticosteroids in the treatment of croup.
Since the 1960s, corticosteroids have been used in the treatment of laryngotracheobronchitis, commonly called croup. Initially, their use for croup was controversial and highly debated in the literature. The evidence over the last 2 decades has strongly favored corticosteroid use in croup management. It has now become the standard of care to use corticosteroids in moderate-to-severe croup. Corticosteroid use in these patients has been shown to reduce hospitalizations, length of illness, and subsequent treatments when compared with placebo. By extrapolation, corticosteroids may even play a role in patients with milder croup presenting for medical assessment. The current recommendation is to treat patients with moderate-to-severe croup with oral dexamethasone in a dose of 0.6 mg/kg (maximum 10-12 mg) because of its ease of administration, easy availability, and low cost. Intramuscular dexamethasone is reserved for patients who are vomiting or who are in severe respiratory distress and unable to tolerate oral medication. Nebulized budesonide, used commonly in some geographic locations, has been found to be effective, but is often not used in favor of the oral corticosteroids. Controversy still exists over the use of corticosteroids in mild and potentially self-limiting disease. Some evidence exists for treating these patients; some clinicians use corticosteroids for all patients with croup who seek care regardless of the severity of the illness. Patients with mild disease may be candidates for lower doses of dexamethasone such as 0.15-0.3 mg/kg. Corticosteroid-induced complications in croup are rare. Overall, corticosteroids have gained universal acceptance for the treatment of croup and have been found to be effective, well tolerated, and inexpensive.
Administration, Inhalation↗
Successful treatment of fungus ball in a patient with allergic bronchopulmonary aspergillosis: continuous percutaneous instillation of antifungal agents into the cavity.
A 53-year-old male of allergic bronchopulmonary aspergillosis (ABPA) with pulmonary fungus ball, who had been administered steroid and suffered repeatedly from dyspnea, was treated successfully with continuous percutaneous instillation of antifungal agents into the cavity. Although the pulmonary fungus ball in his left upper lobe was thought to be worsening ABPA, oral and intravenous antifungal agents failed to improve the clinical course. We selected to use continuous instillation of antifungal agents via an indwelling catheter which was inserted percutaneously into the cavity. Although the instillation of fluconazole (FCZ) for four weeks did not alter the process, two-week instillation of amphotericin B (AMPH) caused disappearance of the fungus ball. We measured the plasma concentration of FCZ and AMPH during their instillation into the cavity to ascertain this treatment to be free from side effects pharmacokinetically.
Administration, Inhalation↗
[Clinical study on bronchial asthma and leukotriene antagonists].
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Administration, Inhalation↗
Non-injection routes for allergen immunotherapy: focus on sublingual immunotherapy.
Allergen specific immunotherapy, together with drugs and allergen avoidance, is a cornerstone in the management of respiratory allergy. The non-injection or local routes were developed with the main goal of improving the safety and minimizing the risk of those side effects, which can accompany the injection route. The pure oral route and the bronchial route showed, in the clinical trials, only a marginal efficacy with not negligible side effects. Therefore, these routes are no longer recommended for clinical use. The nasal route proved effective and safe, but its efficacy is strictly limited to the nose. Moreover, the practical problems with administration have made the use of nasal immunotherapy progressively declining. The efficacy of the sublingual route is confirmed by numerous controlled trials, and a meta analysis (in allergic rhinitis). The safety profile, as derived from clinical trials and post marketing surveillance studies, is satisfactory, with mild gastrointestinal complaints being the more frequent side effect reported. Recent studies have also demonstrated that SLIT has a long-lasting effect and a preventive effect on the onset of new skin sensitizations, and interesting data on adherence and mechanisms of action have become recently available. Based on these experimental data, SLIT is now officially accepted as a viable alternative to the subcutaneous route in adults and children. Several points still need to be elucidated, including: mechanisms of action, optimal dosages, and indications in pediatric patients.
Administration, Inhalation↗
Concept, strategies, and feasibility of noninvasive insulin delivery.
OBJECTIVE: To comprehensively review the progress to date on the development of alternative routes for insulin delivery. RESEARCH DESIGN AND METHODS: Study data were collected through a Medline review. RESULTS: Proof of principle has been established for many routes of administration including dermal, nasal, oral, buccal, and pulmonary insulin delivery. CONCLUSIONS: Of all the approaches to date, pulmonary delivery appears to be most feasible. Ongoing phase III studies will ultimately determine safety, tolerability, and efficacy before approval for clinical use.
Administration, Inhalation↗
Antigen and lipopolysaccharide play synergistic roles in the effector phase of airway inflammation in mice.
T helper (Th) cells play major roles in orchestrating asthmatic airway inflammation, but the molecular mechanisms controlling Th-cell recruitment to the airways remain incompletely defined. Innate immunity contributes importantly to the recruitment of effector T cells into sites of inflammation. To understand better the role of innate immune signals in the development of airway inflammation, we used a murine model in which lipopolysaccharide (LPS) contaminating the antigen is thought to trigger Toll-like receptor 4 (TLR4). To investigate the importance of the TLR4-signaling pathway in induction of lung inflammation, we compared recruitment of adoptively transferred ovalbumin-specific Th1 and Th2 cells in wild-type and TLR4 mutant (TLR4m) mice after intranasal or aerosol challenge. Intranasal challenge of TLR4m mice with ovalbumin resulted in decreased recruitment of Th1 and Th2 cells compared with that of wild-type mice. The numbers of Th1 and Th2 cells recruited to the airways of TLR4m mice were less profoundly reduced after aerosol ovalbumin challenge. Comparing the effects of altering the dose of ovalbumin with that of LPS suggested that both contribute to the magnitude of the response in wild-type mice. Our findings demonstrate the importance of both antigen and endotoxin acting in a synergistic manner in the development of airway inflammation.
Administration, Inhalation↗
Clinical relevance of growth studies.
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Administration, Inhalation↗