Best Route Of Administration Research Articles

Anemia perniciosa en paciente joven: ¿cuál es la mejor vía de administración de la vitamina B12?

Anemia perniciosa en paciente joven: ¿cuál es la mejor vía de administración de la vitamina B12?

The AMPA receptor antagonist perampanel in the adjunctive treatment of partial-onset seizures: clinical trial evidence and experience.

More than 20 antiepileptic drugs (AEDs) are currently available for the medical treatment of epilepsies. However, still about 30% of all epilepsies have a drug-resistant course. Even worse, in the case of some epilepsy syndromes, freedom from seizures is almost never achieved. Therefore, new treatment options are still necessary, especially if theoretical concepts such as a new mode of action offer new horizons. Perampanel is the first-in-class orally active, selective, noncompetitive antagonist of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. The pharmacokinetic profile offers once-daily dosing in the evening as the best route of administration. According to the results of three pivotal placebo-controlled, double-blind phase III trials that investigated perampanel as an adjunctive AED in adult and adolescent patients from age 12 years who had ongoing focal epileptic seizures despite receiving one to three AEDs, perampanel has been widely licensed and introduced. Phase III trials showed superiority of adjunctive perampanel over placebo consistently in the range between 4 and 12 mg. Dizziness and somnolence were by far the leading adverse events. This review covers the clinical trial evidence but also clinical experience with perampanel after launch according to observational studies.

Which is the best route of administration for cell therapy in experimental model of small-for size syndrome in rats?

To evaluate which is the best route of administration for cell therapy in experimental rat model of small-for size syndrome. A total of 40 rats underwent partial hepatectomy (70%) that induces the small-for-size syndrome and were divided into four groups of route administration: intravenous, intraperitoneal, enteral and tracheal. The small-for-size syndrome model was designed with extended partial hepatectomy (70%). The animals were divided into four groups of routes administration: intravenous (n=10) - intravenously through the dorsal vein of the penis; intraperitoneal (n=10) - intraperitoneally in the abdominal cavity; enteral (n=10) - oroenteral with the placement of a number 4 urethral probe and maintained at third duodenal portion; tracheal (n=10) - after tracheal intubation. We track the animals and monitor them for 21 days; during this follow-up we evaluated the result of cell therapy application tracking animals using ultrasound, radiography and PET-scan. Statistical analysis was performed using GraphPad Prism Software(r). Differences were considered significant with the p<0.05. Data are presented as the median and variation for continuous variables. Comparisons between groups were made using analysis of the imaging test by the researchers. All four groups underwent partial hepatectomy of 70% liver tissue targeting the same weight of resected liver. Initially the PET-scan tests showed similarity in administered cells by different routes. However, in few days the route of intravenous administration showed to be the most appropriated to lead cells to the liver followed by enteral. The tracheal and peritoneal routes were not as much successful for this goal. The intravenous route is the best one to cell therapy in experimental rat model of small-for size-syndrome.

Intratracheal Bleomycin Aerosolization: The Best Route of Administration for a Scalable and Homogeneous Pulmonary Fibrosis Rat Model?

Idiopathic pulmonary fibrosis (IPF) is a chronic disease with a poor prognosis and is characterized by the accumulation of fibrotic tissue in lungs resulting from a dysfunction in the healing process. In humans, the pathological process is patchy and temporally heterogeneous and the exact mechanisms remain poorly understood. Different animal models were thus developed. Among these, intratracheal administration of bleomycin (BML) is one of the most frequently used methods to induce lung fibrosis in rodents. In the present study, we first characterized histologically the time-course of lung alteration in rats submitted to BLM instillation. Heterogeneous damages were observed among lungs, consisting in an inflammatory phase at early time-points. It was followed by a transition to a fibrotic state characterized by an increased myofibroblast number and collagen accumulation. We then compared instillation and aerosolization routes of BLM administration. The fibrotic process was studied in each pulmonary lobe using a modified Ashcroft scale. The two quantification methods were confronted and the interobserver variability evaluated. Both methods induced fibrosis development as demonstrated by a similar progression of the highest modified Ashcroft score. However, we highlighted that aerosolization allows a more homogeneous distribution of lesions among lungs, with a persistence of higher grade damages upon time.

PO-0492 A Literature Review Of Current Management Of Patent Ductus Arteriosus In Neonates

Background Recent controversy has sparked interest into a potential new treatment for patent ductus arteriosus (PDA). Ten case series and two randomised controlled trials have now been carried out comparing paracetamol and ibuprofen. This review aims to investigate whether paracetamol could potentially be used as the new first line therapeutic option. Method Literature review. Results Eight out of the ten case series show that paracetamol was effective at closing the PDA in 71–100% of patients. Both randomised control trials were able to show that there was no statistically significant difference between the treatment regimes. One study also provided evidence that paracetamol causes fewer side effects than ibuprofen. Conclusion From the data available it does seem that paracetamol is a viable and potentially better therapeutic option for the treatment of PDA. This is due to it being as successful at closing PDAs with potentially fewer side effects. Further work should now be carried out to answer the limitations of the studies already available to. What is the optimum dose and treatment regime? What is the best route of administration and does treatment alter long-term outcomes?

Inhaled Colistin for Treatment of Pneumonia due to Colistin-Only-SusceptibleAcinetobacter baumannii

PurposeColistin is used for the treatment of pneumonia associated with multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. However, the best route of administration and dosage is not known. We report our experience with aerosolized colistin in twelve patients with pneumonia caused by colistin-only-susceptible (COS) A. baumannii.Materials and MethodsWe retrospectively reviewed patients' medical records who were treated with aerosolized colistin for the treatment of pneumonia.ResultsTen patients were treated only with aerosolized colistin inhalation and two patients received a 3-day course intravenous colistin, and then switched to colistin inhalation therapy. The median duration of aerosolized colistin therapy was 17 days (5-31 days). Four patients were treated only with aerosolized colistin, whereas 4 patients received concomitant glycopeptides, and 4 received concomitant levofloxacin or cefoperazone/sulbactam. At the end of the therapy, the clinical response rate and bacteriological clearance rate was 83% and 50%, respectively. Colistin-resistant strains were isolated from 3 patients after aerosolized colistin therapy; however, all of them showed favorable clinical response. The median interval between inhalation therapy and resistance was 7 days (range 5-19 days). Acute kidney injury developed in 3 patients. Two patients experienced Clostridium difficile associated diarrhea. One patient developed fever and skin rash after aerosolized colistin therapy. No patient developed neurotoxicity or bronchospasm.ConclusionColistin inhalation therapy is deemed tolerable and safe, and could be beneficial as an adjuctive therapy for the management of pneumonia due to COS A. baumannii. However, the potential development of colistin resistance cannot be overlooked.

Lessons from the RAMPART study—and which is the best route of administration of benzodiazepines in status epilepticus

Early treatment of prolonged seizures with benzodiazepines given intravenously by paramedics in the prehospital setting had been shown to be associated with improved outcomes, but the comparative efficacy and safety of an intramuscular (IM) route, which is faster and consistently achievable, was previously unknown. RAMPART (the Rapid Anticonvulsant Medication Prior to Arrival Trial) was a double-blind randomized clinical trial to determine if the efficacy of intramuscular (IM) midazolam is noninferior by a margin of 10% to that of intravenous (IV) lorazepam in patients treated by paramedics for status epilepticus (SE). In children and adults with >5min of convulsions and who are still seizing at paramedic arrival, midazolam administered by IM autoinjector was noninferior to IV lorazepam on the primary efficacy outcome with comparable safety. Patients treated with IM midazolam were more likely to have stopped seizing at emergency department (ED) arrival, without emergency medical services (EMS) rescue therapy, and were less likely to require any hospitalization or admission to an intensive care unit. Lessons from the RAMPART study's findings and potential implications on clinical practice, on the potential role of other routes of administration, on the effect of timing of interventions, and on future clinical trials are discussed.

Perilesional intrathecal administration of autologous bone marrow stromal cells achieves functional improvement in pigs with chronic paraplegia

Background aimsAt present, on the basis of the great number of preclinical studies and preliminary clinical trials in humans, bone marrow stromal cell (BMSC) transplantation offers promise in the treatment of paraplegia. Nevertheless, there is not enough experience in humans about the best candidates for this type of cell therapy or details about the best parameters or best route of administration. MethodsTwo adult paraplegic pigs with chronic paraplegia were treated only with perilesional intrathecal administration of 40 × 106 autologous BMSC suspended in autologous plasma and followed for 1 year after cell transplantation. ResultsOur study showed clinical improvement, starting at 2 mo after BMSC administration and reaching stabilization at 10 mo. This was associated with recovery of previously abolished somatosensory-evoked potentials. At the end of the study, histological images suggested spinal cord regeneration. ConclusionsOur present findings suggest the possible utility of perilesional intrathecal administration of autologous BMSC in patients with chronic paraplegia.

Meta-Analysis of Stem Cell Therapy in Chronic Ischemic Cardiomyopathy

Studies investigating bone marrow stem cell therapy (BMSCT) in patients with chronic ischemic cardiomyopathy have yielded mixed results. A meta-analysis of randomized controlled trials of BMSCT in patients with chronic ischemic cardiomyopathy was undertaken to assess its efficacy and the best route of administration. The MEDLINE, Embase, Cumulative Index to Nursing & Allied Health Literature, and Cochrane Library databases were searched through April 2012 for randomized controlled trials that investigated the impact of BMSCT and its route of administration on left ventricular (LV) function in patients with chronic ischemic cardiomyopathy and systolic dysfunction. Of the 226 reports identified, 10 randomized controlled trials including 519 patients (average LV ejection fraction [LVEF] at baseline 32 ± 7%) were included in the analysis. On the basis of a random-effects model, BMSCT improved the LVEF at 6 months by 4.48% (95% confidence interval [CI] 2.43% to 6.53%, p= 0.0001). A greater improvement in the LVEF was seen with intramyocardial injection compared with intracoronary infusion (5.13% [95% CI 3.17% to 7.10%], p <0.00001, vs 2.32% [95% CI-2.06% to 6.70%], p= 0.30). Overall, there were reductions in LV end-systolic volume of-20.64 ml (95% CI-33.21 to-8.07, p= 0.001) and LV end-diastolic volume of-16.71 ml (95% CI-31.36 to-2.06, p= 0.03). In conclusion, stem cell therapy may improve LVEF and favorably remodel the heart in patients with chronic ischemic cardiomyopathy. On the basis of current limited data, intramyocardial injection may be superior to intracoronary infusion in patients with LV systolic dysfunction.

Use of inhaled versus oral steroids for acute dysphonia

Acute dysphonia is a frequent condition in clinical practice. Its treatment, especially in adults, is not well established in the literature. Steroids are the most recommended drug treatment. However, the existing studies are not enough to establish superiority among the different steroids and the best route of administration. ObjectiveThis prospective clinical study aimed at comparing the effect of inhaling steroids as a dry powder with the effect of oral steroids to treat acute dysphonia. MethodWe assessed 32 adult patients, broken down into two groups of 16 patients in each one of the treatments, before and seven days after the use of the medication. The patients were submitted to videolaryngoscopy and perceptive and acoustic voice assessment. ResultOral and inhalation treatment significantly reduced hyperemia and edema, and improved the muco-ondulatory movement; nonetheless, edema reduction was statistically more significant (p = 0.012) in the patients treated with the inhalation form of the drug. However, comparing the values of the auditory perceptive analysis and the acoustic measures after treatment between the groups was not statistically significant. ConclusionThere was a significant improvement in the acute laryngitis concerning the assessments carried out in all the patients assessed, concerning the two treatments. The inhalation steroid treatment was significantly more effective in reducing the edema.

Colonoscopic versus nasogastric fecal transplantation for the treatment of Clostridium difficile infection: a review and pooled analysis

Fecal microbiota transplantation (FMT) has been demonstrated to be highly effective for the treatment of recurrent Clostridium difficile infection (CDI). However, the best route of administration has not been established. We present a pooled analysis of the reported cases of CDI treated with FMT via colonoscopy or nasogastric tube (NGT) to evaluate treatment efficacy. PubMed was searched for English-written articles published up to December 2011. Studies that reported cases of FMT for recurrent CDI using either colonoscopy or NGT-guided fecal infusion were reviewed. A total of 182 patients from 12 published studies were identified; 148 patients received FMT via colonoscopy (colonoscopy group) and 34 patients received FMT via NGT (NGT group). The median age in the colonoscopy group as compared with the NGT group was 72 and 82 years, respectively. There were differences regarding pre-FMT treatment for CDI; 134 patients (90.5 %, 134/148) received lavage with/without antibiotic in the colonoscopy group and 34 patients (100.0 %, 34/34) received antibiotic without lavage in the NGT group, P < 0.001. A higher stool volume was used for FMT in the colonoscopy group (121 patients, 81.8 %, used 100-400 ml) than in the NGT group (33 patients, 97.0 %, used <100 ml), P < 0.001. The treatment efficacy did not differ significantly; 93.2 % (138/148) success for the colonoscopy group as compared to 85.3 % success (29/34) for the NGT group, P = 0.162. Recurrence of CDI after FMT was also similar in both the colonoscopy group (8/148 5.4 %) versus the NGT group (2/34, 5.9 %), P = 1.000. Despite procedural differences, FMT via colonoscopy or NGT appears to be highly effective and safe for the management of recurrent CDI.

Pain management in heroin and cocaine users

Drug addicts often seek medical help for pain. Numerous fears and beliefs may hinder the recognition, evaluation, and management of pain in addicts. Nevertheless, the same fundamental principles apply to these patients as to other patients in terms of pain evaluation, analgesic selection, and dosage adjustment. Clarity of the medical prescription is crucial. Specific points that require attention in addicts include the effects of the abused drugs on the nociceptive system, the nature and amount of abused drugs, concomitant nondrug addictions, co-morbidities, and the nature of the pain symptoms. Also crucial is differentiating current abusers from former abusers and from abusers taking replacement therapy, as different management strategies are required in these three situations. Detailed information on the history of drug abuse is necessary to avoid unwanted events (e.g., overdosing or withdrawal syndrome) or an exacerbation of the addictive behaviors. In practice, hospital admission should be avoided to the extent possible. The use of strong opioids should be kept to a minimum (although this important rule may be difficult to follow, for instance in surgical emergencies). The best route of administration and galenic formulation vary with each individual situation but, in general, intravenous administration of strong opioids is highly undesirable. A treatment contract established with the patient is crucial and must indicate the nature of the drug or replacement agent used and the treatments given for pain control.

Intraindividual evaluation of the optimal PGE1 application route in critical limb ischemia

Since prostaglandin E1 was first used for the treatment of critical limb ischemia, the best route of administration—intraarterial (i.a.) or intravenous (i.v.)—has not yet been determined. The aim of this study was to compare the effects of i.a. and i.v. prostaglandin E1 (PGE1) infusions on transcutaneous partial pressure of oxygen (tcPO2) on a within-patient basis in patients with critical limb ischemia. In a randomized, crossover study, 20 patients with critical limb ischemia were treated with a 30-minute i.a. infusion of 10 µg PGE1 in 25 ml saline and a 60-minute i.v. infusion of 40 µg PGE1 in 125 ml saline. During i.a. infusion of PGE1, the mean tcPO2 (forefoot) decreased significantly from 12.2 mmHg to 3.3 mmHg (−73%,p<0.001). In contrast, during i.v. infusion of PGE1, tcPO2 (forefoot) increased significantly from 8.9 mmHg to 16.3 mmHg (+83.1%,p<0.001). Administration by both routes also increased tcPO2 measured at the forefoot of the contralateral limb. These results demonstrate that i.v. administration of PGE1 in contrast to the i.a. route significantly improves oxygen supply to the skin, and therefore should be considered superior to i.a. administration.

Abstract LB-293: Perfluorocarbon labeling of human α-type-1-polarized dendritic cells and conventional dendritic cells for in vivo trafficking by fluorine MRI

Abstract Human dendritic cells (DC) have yet to live up to their clinical promise as an immunotherapeutic intervention against cancer, in spite of their in vitro profiles of their ability to effectively prime tumor-specific T cell responses. It is still unclear which is the best route of administration for the most efficient interaction of DC with tumor-specific T cells in patients, and whether the migratory capacity and localization of DC in patients correlates with clinical responsiveness. Here we utilize a perfluorocarbon (PFC) magnetic resonance imaging (MRI) tracer agent which may enable the assessment of the migration and localization of α-type-1-polarized dendritic cells (αDC1) in the clinic. αDC1 producing high levels of interleukin-12p70 with putative strong lymph node homing capabilities, are currently being evaluated clinically for anti-cancer activity. In vivo results demonstrate the capability of 19F MRI to detect and quantify labeled cells with moderate sensitivity, detecting fewer than 1×104 cells per voxel. The lack of endogenous fluorine in the body allows highly-specific 19F MR detection of label and when paired with proton MRI provides clear and quantitative cell localization within their anatomical context. The inertness of this tracking agent on the functional capacity of DC was examined in a panel of in vitro studies. The use of the MRI tracer with both conventional DC and αDC1 indicated similar labeling efficiencies with no observed effect on the DC's ability to stimulate T cell expansion, produce IL-12p70, process antigen or express co-stimulatory and polarizing factors. These data support the clinical translation of this tracer agent to safely track and quantify the administration and migration of human αDC1 by non-invasive 19F MRI in the treatment of cancer patients. An imminent clinical trial of PFC-labeled αDC1 will provide cell tracking data in patients, facilitating advances in greater efficacy in the next generation of DC-based cellular vaccines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-293. doi:10.1158/1538-7445.AM2011-LB-293

Lack of effect of oral administration of resveratrol in LPS-induced systemic inflammation

The high mortality index due to sepsis and the lack of an effective treatment requires the search for new compounds that can serve as therapy for this disease. Resveratrol, a well-known anti-inflammatory natural compound, might be a good candidate for the treatment of sepsis. The aim of this work was to study the effects of oral administration of resveratrol, before and after sepsis initiation, on inflammation markers in a murine model of endotoxin-induced sepsis. Sprague-Dawley male rats were treated with resveratrol the 3 days prior to LPS administration and 45 min later. Hematological parameters, TNF-α, IL-1β and CINC-1, FRAP and TBARS levels were determined. Resveratrol and resveratrol-derived metabolites profile in plasma was compared after oral and intraperitoneal administration. Oral treatment with resveratrol had no apparent systemic protective effects. However, resveratrol reduced the levels of lipid peroxidation in the small intestine and colon. Importantly, the administration of LPS caused a decrease in resveratrol absorption. When resveratrol bioavailability after i.p. administration was compared to that observed after oral administration, a different profile of resveratrol metabolites was found in plasma. These results highlight the importance of studying the bioavailability of the assayed compounds in the experimental models used to be able to choose the best route of administration depending on the target organ and to determine which compounds or derived metabolites are effective treating the studied disease.

Advanced Pain Therapies: Using Methadone, Ketamine, and Lidocaine for Refractory Pain (P14) (Advanced)

1.Describe methadone's unique pharmacokinetic and pharmacodynamic properties and drug-interaction profile.2.Discuss how to convert and manage appropriate patients on both oral and intravenous methadone, using a variety of accepted strategies.3.Describe protocols for the use of lidocaine and ketamine in pain management. Refractory pain management is one of the greatest clinical challenges for clinicians in hospice and palliative care settings. Helping patients who have moved beyond the World Health Organization analgesic ladder requires familiarity with methadone and less commonly used adjuvants such as lidocaine and ketamine. An understanding of methadone's unique pharmacokinetic and pharmacodynamic properties and drug interaction profile is paramount to safely prescribing methadone. Methadone prescribers must also have knowledge of various dosing ratios and methods for converting between methadone and other opioids in order to customize methadone therapy for their patients. Furthermore, prescribers of intravenous methadone must be familiar with recently published consensus guidelines for optimizing analgesia with parenteral methadone. Following didactic presentations, attendees working in small groups will apply the basic principles of methadone prescribing to patient cases that enable them to develop comfort with using methadone for pain management. Finally, the use of lidocaine and ketamine for the treatment of refractory pain will be discussed, with a focus on determining the best route of administration and dosages. Suggestions for developing protocols for their use will be offered. Physical Aspects of Care

Pharmacokinetic and pharmacodynamic evaluation of the lantibiotic MU1140

Presented are the pharmacokinetics (PK), exposure–response relationship, and the PK/pharmacodynamic (PD) index predictive of maximum therapeutic efficacy for the lantibiotic MU1140. MU1140, at a dose of 12.5 or 25 mg/kg, was administered intravenously, to characterize its PK parameters in rat. The recently developed in vitro PD model of MU1140 activity was enhanced by incorporation of the PK of MU1140 in rat. The linked PK/PD model was used in a simulation study to determine the PK/PD index predictive of in vivo efficacy. MU1140 total plasma concentration–time profiles declined biexponentially with elimination terminal half‐life of 1.6 ± 0.1 h. Rapid injection of MU1140 was associated with a hypersensitivity reaction that can be blocked by premedication with diphenhydramine. The simulation study revealed that Staphylococcus aureus concentrations correlated with T > MIC making it the PK/PD index best predictive of efficacy. Collectively, these findings suggest that the best route of administration of MU1140 is slow infusion which will increase the time its concentration remains above the MIC, thus maximizing the therapeutic effect and minimizing the observed toxicity. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2521–2528, 2010

Addressing the Challenge: Current and Future Directions in Ovarian Cancer Therapy

Numerous ovarian gene therapy strategies are in clinical phases based on concepts of replacement/ knock out of deregulated gene, suicide gene strategies, strengthening of the immune response against a tumor, inhibition of tumor angiogenesis and growth factors. Non-viral delivery systems have potential advantages over currently widely used viral vectors and other classical vectors for delivering therapeutic gene of interest. The present review provides a comprehensive overview of potential of various delivery systems currently in use. Non-viral formulations used in ovarian gene therapy include injecting naked DNA, liposomes, polyplexes, lipopolyplexes, nanoparticles, gene gun and ultrasound/microbubble mediated gene delivery. In addition to improving vector delivery, the DNA constructs need to be optimised for both efficient and long-term transgene expression. Minicircles using minimal immunological defined gene expression (MIDGE) technology, are a promising future alternative to plasmid for use in non-viral ovarian gene therapy in terms of biosafety, improved gene transfer, potential bioavailability, minimal size and little immune reaction. The review explores the best route of administration for ovarian cancer gene therapy given its peritoneal dissemination which poses a major challenge in treating ovarian cancer patients. Enhancement of therapeutic index can be further achieved by overcoming barriers both at cellular and nuclear levels. Selective tumor targeting with minimal toxicity using folate modified, incorporating nuclear localization signal and PEGylated stealth liposome's represents a popular approach and needs to be exploited in ovarian gene therapy.

Loop Diuretics in Acute Decompensated Heart Failure

Acute decompensated heart failure (ADHF) is a common and highly morbid cardiovascular disorder. Most hospitalizations for ADHF are related to symptoms of congestion, and the vast majority of ADHF patients are treated with intravenous loop diuretics. Despite this nearly ubiquitous use, data supporting the safety and efficacy of loop diuretics in ADHF are limited, and controversy exists about the best way to use loop diuretics with regard to both dosing and means of administration (continuous infusion vs. intermittent boluses). We reviewed the data supporting the safety and efficacy of loop diuretics in patients with ADHF. A large body of observational literature suggests that loop diuretics, especially at higher doses, may be associated with increased mortality in patients with heart failure even after detailed adjustment for other measures of disease severity. Additionally, multiple small underpowered trials suggest that continuous infusion may be equivalent or superior to intermittent bolus dosing. In summary, there is a critical need to develop more robust data on the use of loop diuretics in ADHF. In that context, the NIH Heart Failure Clinical Research Network has begun the Diuretics Optimization Strategies Evaluation (DOSE) study, a multi-center, double-blind, randomized controlled trial that will enroll 300 patients with ADHF. The DOSE study will randomize patients using a 2 × 2 factorial design to low dose vs. high dose furosemide, and intermittent bolus vs. continuous infusion. Successful completion of the DOSE study will provide important data on the optimal clinical use of loop diuretics in ADHF.

The complex role of fibrin in acute lung injury

in the last decade there have been many advances in our understanding of the pathogenesis of acute lung injury (ALI), but there have been frustratingly few successful therapeutic interventions. In fact, the only treatment proven to reduce mortality is low tidal volume lung-protective mechanical