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Current Rheumatology Reports Dec 2023This review aims to critically evaluate the potential benefit of either oral or subcutaneous administration of methotrexate (MTX) in various immune-mediated inflammatory... (Review)
Review
PURPOSE
This review aims to critically evaluate the potential benefit of either oral or subcutaneous administration of methotrexate (MTX) in various immune-mediated inflammatory disorders (IMIDs) through analysis of efficacy, toxicity, pharmacokinetics and pharmacodynamics of both administration routes.
RECENT FINDINGS
Recent studies comparing the efficacy of oral versus subcutaneous MTX administration in IMIDs have revealed contradicting results. Some reported higher efficacy with subcutaneous administration, while others found no significant difference. Regarding toxicity, some studies have challenged the notion that subcutaneous administration is better tolerated than oral administration, while others have supported this. Pharmacokinetic studies suggest higher plasma bioavailability and increased accumulation of MTX-polyglutamates (MTX-PGs) in red blood cells (RBCs) with subcutaneous administration during the initial treatment phase. However, after several months, similar intracellular drug levels are observed with both administration routes. There is no conclusive evidence supporting the superiority of either oral or subcutaneous MTX administration in terms of efficacy and adverse events in IMIDs. Subcutaneous administration leads to higher plasma bioavailability and initial accumulation of MTX-PGs in RBCs, but the difference seems to disappear over time. Given the variable findings, the choice of administration route may be based on shared decision-making, offering patients the option of either oral or subcutaneous administration of MTX based on individual preferences and tolerability. Further research is needed to better understand the impact of MTX-PGs in various blood cells and TDM on treatment response and adherence to MTX therapy.
Topics: Humans; Methotrexate; Antirheumatic Agents; Injections, Subcutaneous; Administration, Oral; Immunomodulating Agents
PubMed: 37768405
DOI: 10.1007/s11926-023-01116-7 -
Molecules (Basel, Switzerland) Apr 2020Although the global prevalence of neurological disorders such as Parkinson's disease, Alzheimer's disease, glioblastoma, epilepsy, and multiple sclerosis is steadily... (Review)
Review
Although the global prevalence of neurological disorders such as Parkinson's disease, Alzheimer's disease, glioblastoma, epilepsy, and multiple sclerosis is steadily increasing, effective delivery of drug molecules in therapeutic quantities to the central nervous system (CNS) is still lacking. The blood brain barrier (BBB) is the major obstacle for the entry of drugs into the brain, as it comprises a tight layer of endothelial cells surrounded by astrocyte foot processes that limit drugs' entry. In recent times, intranasal drug delivery has emerged as a reliable method to bypass the BBB and treat neurological diseases. The intranasal route for drug delivery to the brain with both solution and particulate formulations has been demonstrated repeatedly in preclinical models, including in human trials. The key features determining the efficacy of drug delivery via the intranasal route include delivery to the olfactory area of the nares, a longer retention time at the nasal mucosal surface, enhanced penetration of the drugs through the nasal epithelia, and reduced drug metabolism in the nasal cavity. This review describes important neurological disorders, challenges in drug delivery to the disordered CNS, and new nasal delivery techniques designed to overcome these challenges and facilitate more efficient and targeted drug delivery. The potential for treatment possibilities with intranasal transfer of drugs will increase with the development of more effective formulations and delivery devices.
Topics: Administration, Intranasal; Animals; Blood-Brain Barrier; Central Nervous System Diseases; Drug Administration Routes; Drug Carriers; Drug Compounding; Drug Delivery Systems; Humans; Nanoparticles; Permeability; Theranostic Nanomedicine
PubMed: 32326318
DOI: 10.3390/molecules25081929 -
Neuron Nov 2002Brain drug development of either small molecule or large molecule (recombinant proteins, gene medicines) neurotherapeutics has been limited, owing to the restrictive... (Review)
Review
Brain drug development of either small molecule or large molecule (recombinant proteins, gene medicines) neurotherapeutics has been limited, owing to the restrictive transport properties of the brain microvasculature, which forms the blood-brain barrier (BBB) in vivo. Widespread drug delivery to the brain, while not feasible via craniotomy and intracerebral injection, is possible if the drug is delivered to brain via the transvascular route through the BBB. Novel brain drug delivery and drug targeting strategies can be developed from an understanding of the molecular and cellular biology of the brain microvascular and BBB transport processes.
Topics: Animals; Blood-Brain Barrier; Brain; Carrier Proteins; Central Nervous System Diseases; Drug Administration Routes; Endothelium, Vascular; Genetic Therapy; Humans; Microcirculation; Tight Junctions
PubMed: 12441045
DOI: 10.1016/s0896-6273(02)01054-1 -
Archives of Razi Institute Jun 2023In the transdermal drug delivery system, the drug is administered through the skin and attains a systemic effect. It is a drug administration route that includes drug...
In the transdermal drug delivery system, the drug is administered through the skin and attains a systemic effect. It is a drug administration route that includes drug transport to the epidermis and potentially dermal tissue of the skin for locally therapeutic effect, while an exceptionally significant drug division is transported in systemic blood circulation. This study aimed to formulate rasagiline mesylate (RM) as a transdermal microneedle (MN) delivery. The RM is an antiparkinson drug that can be classified as class III with low permeability and subjected to extensive first-pass metabolism. At first, it was formulated as nanoparticles using the chitosan polymer and ion gelation method. Afterward, the prepared nanoparticles were incorporated into a transdermal MN formulated by a polydimethylsiloxane template. The two-step casting process uses two polymer concentrations of polyvinyl alcohol and mixes them with other polymers in a 3:1 ratio (polyvinylpyrrolidone and chitosan) and glycerin as a plasticizer. The selected MN formula was MN4 with a promising shape, no bubbles, fine and well-formed sharp needles that passed the folding endurance test with 130 folding times before broken, drug content of 97±10.02%, and permeation. The results showed a significant (>0.05) permeability enhancement and increase of flux (160%), compared to the transdermal patch. The RS polymeric nanoparticles were successfully prepared and loaded within dissolving MNs of sufficient mechanical strength to penetrate the stratum corneum and enhance the amount permeated through it to induce the systemic effect transdermally.
Topics: Animals; Chitosan; Administration, Cutaneous; Skin; Nanoparticles
PubMed: 38028835
DOI: 10.22092/ARI.2022.360192.2562 -
Journal of Travel Medicine 2006Emergency medicine must often cope with harsh climates far below freezing point or high temperatures, and sometimes, an alternative to the normal route of drug... (Review)
Review
Emergency medicine must often cope with harsh climates far below freezing point or high temperatures, and sometimes, an alternative to the normal route of drug administration is necessary. Most of this information is not yet published. Therefore, we summarized the information about these topics for most drugs used in medical emergencies by combining literature research with extensive personal communications with the heads of the drug safety departments of the companies producing these drugs. Most drugs can be used after temperature stress of limited duration. Nevertheless, we recommend replacing them at least once per year or after extreme heat. Knowledge about drugs used in extreme environments will be of increasing importance for medical personnel because in an increasingly mobile society, more and more people, and especially elderly -often with individual medical risks-travel to extreme regions such as tropical or arctic regions or to high altitude, and some of them need medical care during these activities. Because of this increasing need to use drugs in harsh climates (tourism, expeditions, peace corps, military, etc) the actual International Congress of Harmonization recommendations should be added with stability tests at +50 degrees C, freezing and oscillating temperatures, and UV exposure to simulate the storage of the drugs at "outdoor conditions."
Topics: Climate; Drug Administration Routes; Drug Labeling; Drug Packaging; Drug Stability; Drug Storage; Emergency Medical Services; Global Health; Health Knowledge, Attitudes, Practice; Humans; Temperature; Tropical Climate
PubMed: 16412107
DOI: 10.1111/j.1708-8305.2006.00007.x -
AAPS PharmSciTech Mar 2011Transdermal delivery of peptides and proteins avoids the disadvantages associated with the invasive parenteral route of administration and other alternative routes such... (Review)
Review
Transdermal delivery of peptides and proteins avoids the disadvantages associated with the invasive parenteral route of administration and other alternative routes such as the pulmonary and nasal routes. Since proteins have a large size and are hydrophilic in nature, they cannot permeate passively across the skin due to the stratum corneum which allows the transport of only small lipophilic drug molecules. Enhancement techniques such as chemical enhancers, iontophoresis, microneedles, electroporation, sonophoresis, thermal ablation, laser ablation, radiofrequency ablation and noninvasive jet injectors aid in the delivery of proteins by overcoming the skin barrier in different ways. In this review, these enhancement techniques that can enable the transdermal delivery of proteins are discussed, including a discussion of mechanisms, sterility requirements, and commercial development of products. Combination of enhancement techniques may result in a synergistic effect allowing increased protein delivery and these are also discussed.
Topics: Administration, Cutaneous; Drug Delivery Systems; Electroporation; Humans; Iontophoresis; Laser Therapy; Proteins; Skin; Skin Absorption
PubMed: 21369712
DOI: 10.1208/s12249-011-9601-6 -
BioMed Research International 2022Sumatriptan (ST) is a commonly prescribed drug for treating migraine. The efficiency of several routes of ST administration has been investigated. Recently, the... (Review)
Review
Sumatriptan (ST) is a commonly prescribed drug for treating migraine. The efficiency of several routes of ST administration has been investigated. Recently, the intranasal route with different delivery systems has gained interest owing to its fast-acting and effectiveness. The present study is aimed at reviewing the available studies on novel delivery systems for intranasal ST administration. The oral route of ST administration is common but complicated with some problems. Gastroparesis in patients with migraine may reduce the absorption and effectiveness of ST upon oral use. Furthermore, the gastrointestinal (GI) system and hepatic metabolism can alter the pharmacokinetics and clinical effects of ST. The bioavailability of conventional nasal liquids is low due to the deposition of a large fraction of the delivered dose of a drug in the nasal cavity. Several delivery systems have been utilized in a wide range of preclinical and clinical studies to enhance the bioavailability of ST. The beneficial effects of the dry nasal powder of ST (AVP-825) have been proven in clinical studies. Moreover, other delivery systems based on microemulsions, microspheres, and nanoparticles have been introduced, and their higher bioavailability and efficacy were demonstrated in preclinical studies. Based on the extant findings, harnessing novel delivery systems can improve the bioavailability of ST and enhance its effectiveness against migraine attacks. However, further clinical studies are needed to approve the safety and efficacy of employing such systems in humans.
Topics: Administration, Intranasal; Administration, Oral; Drug Delivery Systems; Humans; Migraine Disorders; Serotonin 5-HT1 Receptor Agonists; Sumatriptan; Treatment Outcome
PubMed: 35075426
DOI: 10.1155/2022/3692065 -
Pharmacological Reports : PR Apr 2023Clinical management of COVID-19 has been a daunting task. Due to the lack of specific treatment, vaccines have been regarded as the first line of defence. Innate... (Review)
Review
Clinical management of COVID-19 has been a daunting task. Due to the lack of specific treatment, vaccines have been regarded as the first line of defence. Innate responses and cell-mediated systemic immunity, including serum antibodies, have been the primary focus of practically all studies of the immune response to COVID-19. However, owing to the difficulties encountered by the conventional route, alternative routes for prophylaxis and therapy became the need of the hour. The first site invaded by SARS-CoV-2 is the upper respiratory tract. Nasal vaccines are already in different stages of development. Apart from prophylactic purposes, mucosal immunity can be exploited for therapeutic purposes too. The nasal route for drug delivery offers many advantages over the conventional route. Besides offering a needle-free delivery, they can be self-administered. They present less logistical burden as there is no need for refrigeration. The present article focuses on various aspects of nasal spray for eliminating COVID-19.
Topics: Humans; COVID-19; Nasal Sprays; SARS-CoV-2; Administration, Intranasal; Vaccines
PubMed: 36848033
DOI: 10.1007/s43440-023-00463-7 -
Annals of Internal Medicine Dec 2017Naloxone is effective for reversing opioid overdose, but optimal strategies for out-of-hospital use are uncertain. (Review)
Review
BACKGROUND
Naloxone is effective for reversing opioid overdose, but optimal strategies for out-of-hospital use are uncertain.
PURPOSE
To synthesize evidence on 1) the effects of naloxone route of administration and dosing for suspected opioid overdose in out-of-hospital settings on mortality, reversal of overdose, and harms, and 2) the need for transport to a health care facility after reversal of overdose with naloxone.
DATA SOURCES
Ovid MEDLINE (1946 through September 2017), PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL, U.S. Food and Drug Administration (FDA) materials, and reference lists.
STUDY SELECTION
English-language cohort studies and randomized trials that compared different doses of naloxone, administration routes, or transport versus nontransport after reversal of overdose with naloxone. Main outcomes were mortality, reversal of overdose, recurrence of overdose, and harms.
DATA EXTRACTION
Dual extraction and quality assessment of individual studies; consensus assessment of overall strength of evidence (SOE).
DATA SYNTHESIS
Of 13 eligible studies, 3 randomized controlled trials and 4 cohort studies compared different administration routes. At the same dose (2 mg), 1 trial found similar efficacy between higher-concentration intranasal naloxone (2 mg/mL) and intramuscular naloxone, and 1 trial found that lower-concentration intranasal naloxone (2 mg/5 mL) was less effective than intramuscular naloxone but was associated with decreased risk for agitation (low SOE). Evidence was insufficient to evaluate other comparisons of route of administration. Six uncontrolled studies reported low rates of death and serious adverse events (0% to 1.25%) in nontransported patients after successful naloxone treatment.
LIMITATION
There were few studies, all had methodological limitations, and none evaluated FDA-approved autoinjectors or highly concentrated intranasal formulations.
CONCLUSION
Higher-concentration intranasal naloxone (2 mg/mL) seems to have efficacy similar to that of intramuscular naloxone for reversal of opioid overdose, with no difference in adverse events. Nontransport after reversal of overdose with naloxone seems to be associated with a low rate of serious harms, but no study evaluated risks of transport versus nontransport.
PRIMARY FUNDING SOURCE
Agency for Healthcare Research and Quality. (PROSPERO: CRD42016053891).
Topics: Administration, Intranasal; Analgesics, Opioid; Drug Overdose; Emergency Medical Services; Humans; Injections, Intramuscular; Naloxone; Narcotic Antagonists
PubMed: 29181532
DOI: 10.7326/M17-2224 -
Human Vaccines & Immunotherapeutics Oct 2012IgE-mediated allergy is a highly prevalent disease in the industrialized world. Allergen-specific immunotherapy (SIT) should be the preferred treatment, as it has long... (Review)
Review
IgE-mediated allergy is a highly prevalent disease in the industrialized world. Allergen-specific immunotherapy (SIT) should be the preferred treatment, as it has long lasting protective effects and can stop the progression of the disease. However, few allergic patients choose to undergo SIT, due to the long treatment time and potential allergic adverse events. Since the beneficial effects of SIT are mediated by antigen presenting cells inducing Th1, Treg and antibody responses, whereas the adverse events are caused by mast cells and basophils, the therapeutic window of SIT may be widened by targeting tissues rich in antigen presenting cells. Lymph nodes and the epidermis contain high density of dendritic cells and low numbers of mast cells and basophils. The epidermis has the added benefit of not being vascularised thereby reducing the chances of anaphylactic shock due to leakage of allergen. Hence, both these tissues represent highly promising routes for SIT and are the focus of discussion in this review.
Topics: Animals; Desensitization, Immunologic; Drug Administration Routes; Humans
PubMed: 23095873
DOI: 10.4161/hv.21948