Different Routes Of Drug Administration Research Articles

Study of the Pharmacokinetics and Safety of Dioxidine®, Solution for Topical and External Use, 0.25 mg/ml, in Various Routes of Administration

Topical use of antibacterial drugs as part of complex therapy for purulent-inflammatory infections of the skin and oropharynx can not only eliminate the symptoms but also influence the cause of the disease. Dioxidine® is a broad-spectrum antibacterial drug, active against both gram-positive and gram-negative bacteria. The aim of this study was to investigate the bioavailability, pharmacokinetic parameters, and safety profile of Dioxidine®, solution for topical and external use, 0.25 mg/ml, in cutaneous and topical application. Another dosage form of Dioxidine® — a solution for infusion and external use, 5 mg/ml — was used as a comparison drug. The study consisted of 4 stages reflecting different routes of drug administration: rinsing the oropharynx (path A), a single irrigation of the oropharynx using a spray nozzle (path B), back skin irrigation (path C), and intravenous administration (path D — for the reference drug). The results of the study made it possible to determine the absolute dose-normalized bioavailability of the study drug in the indicated routes of administration, as well as to evaluate its safety profile.

Changing Trends in Conscious Sedation at Pediatric Dental Offices: A Bibliometric Analysis

The uncooperative behavior of children in the dental office has increased the demand for pharmacological behavior management techniques. Moderate sedation is more effective by providing analgesia and anxiolysis, thereby aiding in carrying out the most comfortable, efficient, and high-quality dental services. There is a need to understand the various aspects such as the choice of drug, method of drug administration, safety, and efficacy. Bibliometrics can reveal significant shifts in research and publication trends. Therefore, this study aimed to perform a bibliometric analysis of the literature on evolving trends in conscious sedation at pediatric dental offices. The bibliometric research used RStudio 2021.09.0+351 for Windows (RStudio, Boston, MA), package "bibliometrix," and VOS viewer software (Centre for Science and Technology Studies, Leiden University, The Netherlands. https://www.vosviewer.com). Elsevier's Scopus database (www.scopus.com) provided the literary data for this study, which were exported in BibTex format. The articles were independently categorized according to the following aspects: (a) annual scholarly output; (b) leading countries or regions; (c) leading journals; (d) productive authors; (e) citations; (f) study design; and (g) distribution of topics. The findings considered 1996 through 2022 and used journals, books, articles, and other sources, totaling 1064 papers, with an average of 10.7 per year. According to the findings, the United States, the United Kingdom, and India were principally leading the field of conscious sedation research. In total, 2433 authors were found through the search. The study identified the nations that are currently researching the topics such as midazolam and nitrous-oxide; this paves the way for future partnerships to strengthen the evidence generated in other topic areas using novel sedatives and exploring the different routes of drug administration, thereby benefiting the scientific community by identifying knowledge gaps and experts in this area of research.

Wireless, noninvasive therapeutic drug monitoring system for saliva measurement toward medication management of schizophrenia

As an efficient patient management tool of precision medicine, decentralized therapeutic drug monitoring (TDM) provides new vision for therapy adherence and health management of schizophrenia in a convenient manner. To dispense with psychologically burdensome blood sampling and to achieve real-time, noninvasive, and continual circulating tracking of drugs with narrow therapeutic window, we study the temporal metabolism of clozapine, an antipsychotic with severe side effect, in rat saliva by a wireless, integrated and patient-friendly smart lollipop sensing system. Highly sensitive and efficient sensing performance with acceptable anti-biofouling property was realized based on the synergistic effect of electrodeposited reduced graphene oxide and ionic liquids in pretreatment-free saliva with low detection limit and good accuracy cross-validated with conventional method. On this basis, continual salivary drug levels with distinctive pharmacokinetics were found in different routes of drug administration. Pilot experiment reveals a strong correlation between blood and saliva clozapine and a positive relationship between drug dosage and salivary drug level, indicating potential applications presented by noninvasive saliva analysis towards patient-centered and personalized pharmacotherapy and adherence management via proposed smart lollipop system.

A Review Literature of Netra Swasthya Upakrama

Shalakyatantra is one of the important branches of Ayurveda dealing with diseases and treatment of organs situated above the clavicle. As it deals with sense organs it is a highly specialized one. One should always make all sincere efforts to protect the eyes and treat eye diseases as it is one of the important sense organs. Ayurvedic literature gives equal importance to the prevention of disease with a cure. Acharyas have explained various regimens and protocols for a healthy life in Dincharya (daily routine) and Rutucharya (seasonal routine). Some of these regimens can be considered to be designed especially for the well-being of eyes like Anjana, Nasya, etc. These therapeutic procedures are useful if done scientifically and followed the protocol. Sushruta has mentioned 76 eye diseases out of which treatable diseases are treated with systemic as well as local treatment. Kriyakalpa is one of the local treatments. Various therapeutic procedures which are formulated with different drugs and different routes of drug administration according to Dosh, Satmya, and Kal have been explained to avoid the diseased condition. Being a local therapeutic procedure, fast action and penetration of drugs through ocular tissue raises the importance of Kriyakalpa in ocular diseases. Likewise, various regimens explained in Dinacharya and Rutucharya are important to maintain ocular health to avoid ocular diseases.

Brain Metabolic Profile after Intranasal vs. Intraperitoneal Clomipramine Treatment in Rats with Ultrasound Model of Depression.

Background: Molecular mechanisms of depression remain unclear. The brain metabolome after antidepressant therapy is poorly understood and had not been performed for different routes of drug administration before the present study. Rats were exposed to chronic ultrasound stress and treated with intranasal and intraperitoneal clomipramine. We then analyzed 28 metabolites in the frontal cortex and hippocampus. Methods: Rats’ behavior was identified in such tests: social interaction, sucrose preference, forced swim, and Morris water maze. Metabolic analysis was performed with liquid chromatography. Results: After ultrasound stress pronounced depressive-like behavior, clomipramine had an equally antidepressant effect after intranasal and intraperitoneal administration on behavior. Ultrasound stress contributed to changes of the metabolomic pathways associated with pathophysiology of depression. Clomipramine affected global metabolome in frontal cortex and hippocampus in a different way that depended on the route of administration. Intranasal route was associated with more significant changes of metabolites composition in the frontal cortex compared to the control and ultrasound groups while the intraperitoneal route corresponded with more profound changes in hippocampal metabolome compared to other groups. Since far metabolic processes in the brain can change in many ways depending on different routes of administration, the antidepressant therapy should also be evaluated from this point of view.

Physiologically Based Pharmacokinetic Modelling of Inhaled Nemiralisib: Mechanistic Components for Pulmonary Absorption, Systemic Distribution, and Oral Absorption.

Background and ObjectivesPhysiologically based pharmacokinetic (PBPK) modelling has evolved to accommodate different routes of drug administration and enables prediction of drug concentrations in tissues as well as plasma. The inhalation route of administration has proven successful in treating respiratory diseases but can also be used for rapid systemic delivery, holding great promise for treatment of diseases requiring systemic exposure. The objective of this work was to develop a PBPK model that predicts plasma and tissue concentrations following inhalation administration of the PI3Kδ inhibitor nemiralisib.MethodsA PBPK model was built in GastroPlus® that includes a complete mechanistic description of pulmonary absorption, systemic distribution and oral absorption following inhalation administration of nemiralisib. The availability of clinical data obtained after intravenous, oral and inhalation administration enabled validation of the model with observed data and accurate assessment of pulmonary drug absorption. The PBPK model described in this study incorporates novel use of key parameters such as lung systemic absorption rate constants derived from human physiological lung blood flows, and implementation of the specific permeability-surface area product per millilitre of tissue cell volume (SpecPStc) to predict tissue distribution.ResultsThe inhaled PBPK model was verified using plasma and bronchoalveolar lavage fluid concentration data obtained in human subjects. Prediction of tissue concentrations using the permeability-limited systemic disposition tissue model was further validated using tissue concentration data obtained in the rat following intravenous infusion administration to steady state.ConclusionsFully mechanistic inhaled PBPK models such as the model described herein could be applied for cross molecule assessments with respect to lung retention and systemic exposure, both in terms of pharmacology and toxicology, and may facilitate clinical indication selection.

Influence of Inosine on Cerebral Hemodynamics in Space Motion Sickness in Experimental Animals.

Motion sickness occurs worldwide in healthy individuals regardless of age, ethnicity, or gender. It is an acute disorder; it can also present as a chronic disorder in some individuals. Motion sickness not only includes vomiting and nausea, but also includes other features such as pallor of varying degrees, cold sweating, headache, drowsiness, increased salivation, and cranial pain, which are severe. Some of the other assessment scales can interpret sickness on exposure to virtual or visual stimulation and while travelling in different types of transport. The aim of our research is to study the effect of the drug on the level of blood flow and vascular reactivity of cerebral vessels when simulating changes in the cerebral circulation in terrestrial conditions characteristic of hypogravity. Chronic experiments were performed on non-anesthetized rabbits with large hemispheres, thalamus and hypothalamus were implanted with the needle-platinum electrodes 150 mm in diameter in the cortex, and local blood flow and vascular reactivity were recorded accordingly. Cerebrovascular disturbances were modeled using an MSAOP (motion sickness of animals in the anti-orthostatic position) with an inclined angle of 45° for 2 hours. Local blood flow (BF) was measured in ml/min/100g of tissue by the method of registration of hydrogen clearance. The vasodilator coefficient of reactivity (CrCO2) was calculated by the ratio of BF against the background of inhalation of a mixture of 7% CO2 with air to the initial BF; vasoconstrictor - in relation to BF on the background of inhalation of 100% O2 to the initial BF (CrO2). A series of experiments were carried out with different routes of drug administration: First, inosine was administered intravenously at a dose of 5 mg/kg immediately before the start of SMS modeling, same dose was administered 30 minutes before the start of exposure. As a control, we used the results of experimental animals under similar conditions without the administration of the drugs. Inosine has pronounced protective properties in cerebrovascular disorders on the background of space motion sickness (SMS) modeling, which is manifested by normalization of BF and restoration of compensatory reactions of cerebral vessels. In the mechanism of cerebroprotective action of inosine, it is able to correct the metabolic processes, which play an important role and help increase the compensatory capabilities and functional stability of the cerebrovascular system under gravitational influences. When using inosine orally, the effects are more pronounced than when administered intravenously, which should be taken into account when using it for the prevention of cerebrovascular disorders in extreme conditions.

ОПРЕДЕЛЕНИЕ КОНЦЕНТРАЦИИ ИЗОНИАЗИДА В СЫВОРОТКЕ КРОВИ БОЛЬНЫХ ТУБЕРКУЛЁЗОМ ЛЁГКИХ С МНОЖЕСТВЕННОЙ ЛЕКАРСТВЕННОЙ УСТОЙЧИВОСТЬЮ ВОЗБУДИТЕЛЯ С ИСПОЛЬЗОВАНИЕМ МЕТОДА ВЫСОКОЭФФЕКТИВНОЙ ЖИДКОСТНОЙ ХРОМАТОГРАФИИ

To study Mycobacterium tuberculosis (MTB) genotypes circulating in the Sakha Republic (Yakutia), molecular genetic analysis of multidrug-resistant MTB was performed using real-time PCR-test. The study showed predominance of Beijing genotype with resistance to isoniazid caused by mutations in kat G gene alone (86.2 %), in both kat G and inh A genes (10.3 %), or in inh A alone (3,5 %). In this work, we studied variations in serum isoniazid concentration in patients with multidrug-resistant tuberculosis, using different routes of drug administration: regional lymphotropic, intravenous infusion (IV), intramuscular injection (IM), and oral. Blood samples were obtained 1.5, 6, and 9 hours after administration of the drug. Levels and variations of isoniazid serum concentrations were assessed at intervals, using high-performance liquid chromatography (HPLC). For assessing the efficiency of treatment, patients were divided to four groups according to isoniazid administration routes. The study established that serum isoniazid concentrations observed with regional lymphotropic administration, were initially the lowest (4.2 mg/L), compared to IV infusion, IM, and oral administration routes (8,12.5, and 17.1 mg/L, respectively), but showed slower reduction of concentration. It was also noticed, that after 9 hours, the serum concentration of isoniazid was reliably higher in regional lymphotropicgroup, than in the rest of study groups (2.2 vs. 0.8 mg/L). Higher therapeutic effect of intralymphatic drug administration could be explained by the formation within the regional lymphatic network of a localized area around the site of injection containing enhanced concentration of isoniazid and allowing extended drug release into bloodstream, resulting further in prolonged drug biotransformation.

Hepatitis C: clinical and biological features related to different forms of cocaine use.

Hepatitis C virus (HCV) infection is related with several liver diseases such as cirrhosis and hepatocellular carcinomas, leading to more than 0.5 million deaths every year and to a great global burden. It is known that injection drug users show a high prevalence of HCV infection, being considered a risk group for this disease. Cocaine users seem to be in greater risk than other drug users, and several hypotheses for this association are being studied. To review data on HCV infection in cocaine users, taking into consideration the relevance of the different routes of drug administration and other risk behaviors. This was a narrative review performed in the main scientific databases. Data suggest that cocaine use could be associated with HCV infection due to the specificities of cocaine consumption pattern, even in those subjects who do not inject drugs, in addition to other risky behaviors, such as tattooing and unprotected sex. Injectable cocaine users seem to be more susceptible to contamination than users who do not inject drugs. However, evidence is pointing to the possibility of infection by sharing drug paraphernalia other than syringes. Moreover, specific immune system impairments caused by cocaine use are also being linked with HCV infection susceptibility, persistence and increased pathological effects.

The effects of treatment failure generalize across different routes of drug administration.

Failure of medical treatments can hamper responses to subsequent treatments. It has been suggested that changing the route of drug administration could reduce such negative carry-over effects, but direct evidence for this approach is lacking. We therefore investigated in 211 healthy volunteers whether changes in drug administration route reduce such carry-over effects. A positive or negative treatment history with topical analgesic treatments was induced experimentally in a mock clinical trial setting. Subsequently, a different inert drug was introduced via the same (topical) or another (oral) route of administration and its analgesic efficacy was tested. Changing the route of drug administration induced expectations of positive treatment effects in the subjects but did not actually counteract the negative carry-over effects on treatment efficacy. These findings indicate that learned carry-over effects generalize over time and across routes of drug administration-independent of conscious expectations. Other strategies are needed to prevent negative carry-over effects of treatment failure from influencing the results of subsequent treatment attempts.

Dendrimers and their Applications: A Review Article

Dendrimers are the valuable additives in different routes of drug administration and are the most successful agents, because dendrimers provide greater biocompatibility, water solubility and bioavailability. In this review, synthesis structures, method of preparation have been discussed. Interaction mechanisms between dendrimer molecules and active pharmaceutical ingredient (API), like simple encapsulation and covalent conjugation and the recent applications of dendrimers have also been focused. Divergent method of poly amidoamine (PAMAM) dendrimers is found to be more applicable as compare to convergent method and PAMAM are also considered as ideal carriers for drug delivery because of large variety of surface groups, high aqueous solubility, and their unique architecture.

Protein and Peptide in Drug Targeting and its Therapeutic Approach

Aim. The main aim of this review article is to provide information like advantages of protein and peptides via different routes of drug administration, targeted to a particular site and its implication in drug delivery system. Methods. To that aim, from the web sites of PubMed, HCAplus, Thomson, and Registry were used as the main sources to perform the search for the most significant research articles published on the subject. The information was then carefully analyzed, highlighting the most important results in the development of protein and peptide drug targeting as well as its therapeutic activity. Results. In recent years many researchers use protein and peptide as a target site of drug by a different delivery system. Proteins and peptides are used as specific and effective therapeutic agents, due to instability and side effects their use is complicated. Protein kinases are important regulators of most, if not all, biological processes. Abnormal activity of proteins and peptides has been implicated in many human diseases, such as diabetes, cancer and neurodegenerative disorders. Conclusions. It is concluded that the protein and peptide were used in drug targeting to specific site and also used in different diseased states like cancer, diabetes, immunomodulating, neurodegenerative effects and antimicrobial activity.

Uveitic macular edema: a stepladder treatment paradigm

The purpose of this review is to evaluate the treatment modalities that are commonly employed for the treatment of uveitis-related macular edema. Herein, the different drug classes used to treat the condition are described. In addition, the effectiveness, benefits and risks of the different routes of drug administration are discussed. Although some treatments have been evaluated in prospective clinical trials, most clinical research has been retrospective in nature. Thus, there is a need for more prospective controlled trials in order to determine which treatment, if any, is superior. A well-defined and nationally accepted treatment approach is needed in order to more effectively manage uveitic macular edema.

Novel non-invasive protein and peptide drug delivery approaches.

Protein and peptide based therapeutics are typically administered by injection due to their poor uptake when administered via enteral routes of drug administration. Unfortunately, chronic administration of these drugs through multiple injections presents certain patient related problems and it is difficult to mimic the normal physiological release patterns via this mode of drug administration. A need therefore exists to non-invasively deliver these drugs by means of alternative ways such as via the oral, pulmonary, nasal, transdermal and buccal administration routes. Although some attempts of needle free peptide and protein drug delivery have progressed to the clinical stage, relatively limited success has been achieved in terms of commercially available products. Despite the low frequency of clinical breakthroughs with noninvasive protein drug delivery this far, it remains an active research area with renewed interest not only due to its improved therapeutic potential, but also due to the attractive commercial outcomes it offers. It is the aim of this review article to reflect on the main strategies investigated to overcome the barriers against effective systemic protein drug delivery in different routes of drug administration. Approaches based on chemical modifications and pharmaceutical technologies are discussed with reference to examples of drugs and devices that have shown potential, while attempts that have failed are also briefly outlined.

Dendrimeric systems and their applications in ocular drug delivery.

Ophthalmic drug delivery is one of the most attractive and challenging research area for pharmaceutical scientists and ophthalmologists. Absorption of an ophthalmic drug in conventional dosage forms is seriously limited by physiological conditions. The use of nonionic or ionic biodegradable polymers in aqueous solutions and colloidal dosage forms such as liposomes, nanoparticles, nanocapsules, microspheres, microcapsules, microemulsions, and dendrimers has been studied to overcome the problems mentioned above. Dendrimers are a new class of polymeric materials. The unique nanostructured architecture of dendrimers has been studied to examine their role in delivery of therapeutics and imaging agents. Dendrimers can enhance drug's water solubility, bioavailability, and biocompatibility and can be applied for different routes of drug administration successfully. Permeability enhancer properties of dendrimers were also reported. The use of dendrimers can also reduce toxicity versus activity and following an appropriate application route they allow the delivery of the drug to the targeted site and provide desired pharmacokinetic parameters. Therefore, dendrimeric drug delivery systems are of interest in ocular drug delivery. In this review, the limitations related to eye's unique structure, the advantages of dendrimers, and the potential applications of dendrimeric systems to ophthalmology including imaging, drug, peptide, and gene delivery will be discussed.

Characteristics of Psychopathology and the Relationship Between Routes of Drug Administration and Psychiatric Symptoms in Heroin Addicts

ABSTRACT The objective of this study was to explore the characteristics of comorbid psychiatric symptoms and the relationship between different routes of drug administration and psychiatric symptoms. Five hundred and nine heroin addicts were studied in Drug Detoxification and Rehabilitation Centers in Yunnan and Heilongjiang provinces of China. The measure instrument, including demographic characteristics, history of drug abuse, and the Symptom Checklist-90 (SCL-90) scale (Chinese version), was administered to eligible heroin addicts. Among the subjects, comorbid psychopathology conditions were more severe on all dimensions of SCL-90 comparing with normal adults and the average score of Depression was highest among the 9 dimensions in heroin addicts; psychiatric symptoms were more severe in heroin injecting group than in “chasing the dragon” group and only the difference in Obsessive-Compulsive was significant, but more significant differences were found between snorting heroin addicts and chasing or injecting heroin addicts, and the average score of each dimension of SCL-90 was higher in the snorting group than in the other 2 groups. The reasons of the results and meaning for the present study are discussed. In summary, comorbid psychiatric symptoms in the heroin addicts were very common and severe and their severity varied with different routes of drug administration, suggesting that routes of drug administration should be considered as an important risk factor to mental health of heroin addicts.

The validation of a functional, isolated pig bladder model for physiological experimentation

Characterizing the integrative physiology of the bladder requires whole organ preparations. The purpose of this study was to validate an isolated large animal (pig) bladder preparation, through arterial and intravesical drug administration, intravesical pressure recording, and filming of surface micromotions. Female pig bladders were obtained from the local abattoir and arterially perfused in vitro. Arterial and intravesical pressures were recorded at varying volumes. Bladder viability was assessed histologically and by monitoring inflow and outflow pH. Arterial drug administration employed boluses introduced into the perfusate. Intravesical administration involved slow instillation and a prolonged dwell-time. Surface micromotions were recorded by filming the separation of surface markers concurrently with intravesical pressure measurement. Adequate perfusion to all bladder layers was achieved for up to 8 h; there was no structural deterioration nor alteration in inflow and effluent perfusate pH. Arterial drug administration (carbachol and potassium chloride) showed consistent dose-dependent responses. Localized movements (micromotions) occurred over the bladder surface, with variable correlation with fluctuations of intravesical pressure. The isolated pig bladder is a valid approach to study integrative bladder physiology. It remains viable when perfused in vitro, responds to different routes of drug administration and provides a model to correlate movements of the bladder wall directly to variation of intravesical pressure.

Differences in tissue drug concentrations following intravenous versus intraperitoneal treatment with amphotericin B deoxycholate or liposomal amphotericin B

Amphotericin B formulations were compared in preclinical models by using intraperitoneal (ip) and intravenous (iv) delivery of amphotericin B deoxycholate (DAMB) or liposomal amphotericin B. We examined the effects on drug tissue penetration and retention resulting from different routes of drug administration. Mice were treated with equivalent total doses of AmBisome (AmBi) or DAMB (i.e.,15 mg/kg) given ip (3 mg/kg/day for 5 days) or iv (3 mg/kg/day AmBi for 5 days or 1 mg/kg/day DAMB for 15 days), with tissues collected 24 h post-treatment. For drug retention studies, mice were given iv or ip total doses of 30 mg/kg AmBi (10 mg/kg/day 3 x /week) or 60 mg/kg AmBi (20 mg/kg/day 3 x /week) with tissue collection 24 h or 7 days post-treatment. Blood samples were collected at 0.5 h, 2 h, 8 h, 12 h and 24 h after ip or iv drug dosing. A Paecilomyces variottii bioassay was used to determine drug concentrations. AmBi and DAMB were detected in the kidneys following iv, but not ip dosing. Significantly more DAMB than AmBi was detected in the lungs with ip dosing (P = 0.008), and more AmBi than DAMB (P = 0.056) was present with iv dosing. Unlike the lungs, the spleen and liver retained the AmBi for up to one week post-treatment regardless of the route of drug administration. Thus, there are significant differences in AmBi and DAMB tissue distribution depending upon the drug route and these differences could effect how the drugs perform in fungal infection models.

Dendrimers as Drug Carriers: Applications in Different Routes of Drug Administration

Dendrimers have successfully proved themselves as useful additives in different routes of drug administration because they can render drugs greater water-solubility, bioavailability, and biocompatibility. This review demonstrated the potential of dendrimers to be applied in these detailed routes with particular reference to intravenous, oral, transdermal, and ocular delivery systems. As a necessary introduction, the structures, synthesis, and properties of dendrimers were presented. Furthermore, the interaction mechanisms between dendrimers and drug molecules, including simple encapsulation, electrostatic interaction, and covalent conjugation, were elaborated.

A novel approach to immunosuppression: targeting the alloimmune mechanisms of graft rejection

Purpose of review Lung transplantation has demonstrated both a survival and quality of life benefit for selected patients with end-stage lung disease. Allograft rejection is common. Chronic allograft rejection is the major life-limiting factor after lung transplantation. The mechanisms of graft rejection are reviewed, providing an insight into the possible targets for therapeutic intervention. Clinical trials of immunosuppression in lung transplantation are reviewed, highlighting the evolving evidence base for the use of the increasing number of immunosuppressive drugs. Recent findings An increasing number of immunosuppressive drugs with different characteristics are available to treat graft rejection. It is possible to tailor immunosuppression to individual clinical scenarios. Different routes of drug administration and drug monitoring have been evaluated, together with other immunomodulatory strategies. The role of anti-human leukocyte antigen antibodies in graft rejection is being evaluated. The role of environmental triggers to graft rejection has been highlighted. Summary The lack of evidence of improvements in long-term survival has led to wide variations in the interpretation of the relevance of clinical trials. The small volume of lung transplants undertaken in individual centres hampers research efforts. Continued collaborative research into the prevention of chronic allograft rejection is essential.