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Brain Research Bulletin Oct 2018The acute or chronic drug treatments for different neurodegenerative and psychiatric disorders are challenging from several aspects. The low bioavailability and limited... (Review)
Review
The acute or chronic drug treatments for different neurodegenerative and psychiatric disorders are challenging from several aspects. The low bioavailability and limited brain exposure of oral drugs, the rapid metabolism, elimination, the unwanted side effects and also the high dose to be added mean both inconvenience for the patients and high costs for the patients, their family and the society. The reason of low brain penetration of the compounds is that they have to overcome the blood-brain barrier which protects the brain against xenobiotics. Intranasal drug administration is one of the promising options to bypass blood-brain barrier, to reduce the systemic adverse effects of the drugs and to lower the doses to be administered. Furthermore, the drugs administered using nasal route have usually higher bioavailability, less side effects and result in higher brain exposure at similar dosage than the oral drugs. In this review the focus is on giving an overview on the anatomical and cellular structure of nasal cavity and absorption surface. It presents some possibilities to enhance the drug penetration through the nasal barrier and summarizes some in vitro, ex vivo and in vivo technologies to test the drug delivery across the nasal epithelium into the brain. Finally, the authors give a critical evaluation of the nasal route of administration showing its main advantages and limitations of this delivery route for CNS drug targeting.
Topics: Administration, Intranasal; Animals; Blood-Brain Barrier; Brain; Drug Administration Routes; Drug Delivery Systems; Humans; Models, Animal; Nasal Cavity; Trigeminal Nerve
PubMed: 30449731
DOI: 10.1016/j.brainresbull.2018.10.009 -
Pharmaceutical Research Dec 2019Intraperitoneal (IP) route of drug administration in laboratory animals is a common practice in many in vivo studies of disease models. While this route is an easy to... (Review)
Review
Intraperitoneal (IP) route of drug administration in laboratory animals is a common practice in many in vivo studies of disease models. While this route is an easy to master, quick, suitable for chronic treatments and with low impact of stress on laboratory rodents, there is a common concern that it may not be an acceptable route for drug administration in experimental studies. The latter is likely due to sparsity of information regarding pharmacokinetics of pharmacological agents and the mechanisms through which agents get systemic exposure after IP administration. In this review, we summarize the main mechanisms involved in bioavailability of IP administered drugs and provide examples of pharmacokinetic profiles for small and large molecules in comparison to other routes of administration. We conclude with a notion that IP administration of drugs in experimental studies involving rodents is a justifiable route for pharmacological and proof-of-concept studies where the goal is to evaluate the effect(s) of target engagement rather than properties of a drug formulation and/or its pharmacokinetics for clinical translation.
Topics: Animals; Biological Availability; Drug Administration Routes; Drug Compounding; Humans; Injections, Intraperitoneal; Injections, Subcutaneous; Models, Animal; Particle Size; Pharmaceutical Preparations; Pharmacokinetics; Signal Transduction
PubMed: 31873819
DOI: 10.1007/s11095-019-2745-x -
International Journal of Pharmaceutics Sep 2020Transdermal drug delivery using microneedles is increasingly gaining interest due to the issues associated with oral drug delivery routes. Gastrointestinal route exposes... (Review)
Review
Transdermal drug delivery using microneedles is increasingly gaining interest due to the issues associated with oral drug delivery routes. Gastrointestinal route exposes the drug to acid and enzymes present in the stomach, leading to denaturation of the compound and resulting in poor bioavailability. Microneedle transdermal drug delivery addresses the problems linked to oral delivery and to relieves the discomfort of patients associated with injections to increase patient compliance. Microneedles can be broadly classified into five types: solid microneedles, coated microneedles, dissolving microneedles, hollow microneedles, and hydrogel-forming microneedles. The materials used for the preparation of microneedles dictate the different applications and features present in the microneedle. Polymeric microneedle arrays present an improved method for transdermal administration of drugs as they penetrate the skin stratum corneum barrier with minimal invasiveness. The review summarizes the importance of polymeric microneedle and discussed some of the most important therapeutic drugs in research, mainly protein drugs, vaccines and small molecule drugs in regenerative medicine.
Topics: Administration, Cutaneous; Drug Delivery Systems; Humans; Microinjections; Needles; Pharmaceutical Preparations; Polymers; Skin
PubMed: 32739388
DOI: 10.1016/j.ijpharm.2020.119673 -
Pharmacogenomics Apr 2018Tacrolimus is prescribed to the majority of transplant recipients to prevent graft rejection, and although patients are maintained on oral administration, nonoral routes... (Review)
Review
Tacrolimus is prescribed to the majority of transplant recipients to prevent graft rejection, and although patients are maintained on oral administration, nonoral routes of administration are frequently used in the initial post-transplant period. CYP3A5 genotype is an established predictor of oral tacrolimus dose requirements, and clinical guideline recommendations exist for CYP3A5-guided dose selection. However, the association between CYP3A5 and nonoral tacrolimus administration is currently poorly understood, and differs from the oral tacrolimus relationship. In addition to CYP3A5, other pharmacogenes associated with CYP3A activity, including CYP3A4, CYP3A7 and POR have also been identified as predictors of tacrolimus exposure. This review will describe the current understanding of the relationship between these pharmacogenes and tacrolimus pharmacokinetics after oral and nonoral administration.
Topics: Administration, Oral; Cytochrome P-450 CYP3A; Drug Administration Routes; Genotype; Graft Rejection; Humans; Kidney Transplantation; Pharmacogenomic Testing; Polymorphism, Single Nucleotide; Tacrolimus
PubMed: 29629825
DOI: 10.2217/pgs-2018-0003 -
Clinical Pharmacokinetics Feb 2016The administration of drugs to neonates poses significant challenges. The aim of this review was to provide insight into some of these challenges and resolutions that... (Review)
Review
The administration of drugs to neonates poses significant challenges. The aim of this review was to provide insight into some of these challenges and resolutions that may be encountered with several of the most commonly used routes of administration and dosage forms in neonatal care, including oral, parenteral, transdermal, intrapulmonary, and rectal. Important considerations include fluctuations in stomach pH hours to years after birth, the logistics of setting up an intravenous infusion, the need for reduced particle size for aerosol delivery to the developing neonatal lung, and variation in perirectal venous drainage. Additionally, some of the recently developed technologies for use in neonatal care are described. While the understanding of neonatal drug delivery has advanced over the past several decades, there is still a deficiency of technologies and formulations developed specifically for this population.
Topics: Drug Administration Routes; Drug Delivery Systems; Humans; Infant, Newborn; Pharmaceutical Preparations
PubMed: 26245673
DOI: 10.1007/s40262-015-0313-z -
The Journal of Clinical Psychiatry Jul 2017Ketamine, administered in subanesthetic doses, is an effective off-label treatment for severe and even treatment-refractory depression; however, despite dozens of... (Comparative Study)
Comparative Study Review
BACKGROUND
Ketamine, administered in subanesthetic doses, is an effective off-label treatment for severe and even treatment-refractory depression; however, despite dozens of studies across nearly 2 decades of research, there is no definitive guidance on matters related to core practice issues.
METHODS
This article presents a qualitative review and summary about what is known about ketamine dosing, rate of administration, route of administration, duration of treatment, and frequency of sessions.
RESULTS
Ketamine is most commonly administered in the dose of 0.5 mg/kg, but some patients may respond to doses as low as 0.1 mg/kg, and others may require up to 0.75 mg/kg. The ketamine dose is conventionally administered across 40 minutes; however, safety and efficacy have been demonstrated in sessions ranging between 2 and 100 minutes in duration. Bolus administration is safe and effective when the drug is administered intramuscularly or subcutaneously. Whereas the intravenous route is the most commonly employed, safety and efficacy have been described with other routes of administration, as well; these include oral, sublingual, transmucosal, intranasal, intramuscular, and subcutaneous routes. Patients may receive a single session of treatment or a course of treatment during the acute phase, and treatment may rarely be continued for weeks to years to extend and maintain treatment gains in refractory cases. When so extended, the ideal frequency is perhaps best individualized wherein ketamine is dosed a little before the effect of the previous session is expected to wear off.
CONCLUSIONS
There is likely to be a complex interaction between ketamine dose, session duration, route of administration, frequency of administration, and related practice. Until definitive studies comparing different doses, rates of administration, routes of administration, and other considerations are conducted, firm recommendations are not possible. From the point of view of clinical practicability, subcutaneous, intranasal, and oral ketamine warrant further study. If domiciliary treatment is considered, the risk of abuse must be kept in mind.
Topics: Antidepressive Agents; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Infusions, Intravenous; Injections, Intramuscular; Injections, Subcutaneous; Ketamine; Treatment Outcome
PubMed: 28749092
DOI: 10.4088/JCP.17f11738 -
International Journal of Biological... May 2020Hyaluronic acid (HA) is a large non-sulphated glycosaminoglycan that is an important component of extracellular matrix (ECM) and a biodegradable polymer. Due to a... (Review)
Review
Hyaluronic acid: A review on its biology, aspects of drug delivery, route of administrations and a special emphasis on its approved marketed products and recent clinical studies.
Hyaluronic acid (HA) is a large non-sulphated glycosaminoglycan that is an important component of extracellular matrix (ECM) and a biodegradable polymer. Due to a variation in its molecular weight, HA derivatives can be utilized to make different formulations like fillers, creams, gels and drops. HA based drug research has seen a recent surge largely due to some properties like mucoadhesion, biocompatibility and ease of chemical modification. Such properties of HA have led to applications in tissue regeneration, anti-aging and anti-inflammatory medications. HA can be conjugated, functionalized or used as a nanocarrier supplement with a definite increase in its cellular uptake and efficiency. HA when encapsulated in a nanocarrier may help to improve the ECM growth and provide a sustained release of agents. This review discusses the mechanistic behavior of HA pertaining to its biological synthesis and degradation. It also discusses the administration of some noteworthy and recent HA based formulations through different routes for application in various physiological conditions along with their ongoing clinical trial updates and approved marketed products.
Topics: Clinical Studies as Topic; Drug Administration Routes; Drug Carriers; Drug Delivery Systems; Guided Tissue Regeneration; Humans; Hyaluronic Acid; Mechanical Phenomena; Molecular Structure
PubMed: 31715233
DOI: 10.1016/j.ijbiomac.2019.11.066 -
International Journal of Toxicology 2006The laboratory toxicologist is frequently faced with the challenge of selecting appropriate vehicles or developing utilitarian formulations for use in in vivo... (Comparative Study)
Comparative Study Review
The laboratory toxicologist is frequently faced with the challenge of selecting appropriate vehicles or developing utilitarian formulations for use in in vivo nonclinical safety assessment studies. Although there are many vehicles available that may meet physical and chemical requirements for chemical or pharmaceutical formulation, there are wide differences in species and route of administration specific to tolerances to these vehicles. In current practice, these differences are largely approached on a basis of individual experience as there is only scattered literature on individual vehicles and no comprehensive treatment or information source. This approach leads to excessive animal use and unplanned delays in testing and development. To address this need, a consulting firm and three contract research organizations conducted a rigorous data mining operation of control (vehicle) data from studies dating from 1991 to present. The results identified 65 single component vehicles used in 368 studies across multiple species (dog, primate, rat, mouse, rabbit, guinea pig, minipig, chick embryo, and cat) by multiple routes. Reported here are the results of this effort, including maximum tolerated use levels by species, route, and duration of study, with accompanying dose limiting toxicity. Also included are basic chemical information and a review of available literature on each vehicle, as well as guidance on volume limits and pH by route and some basic guidance on nonclinical formulation development.
Topics: Animals; Databases, Factual; Drug Administration Routes; Drug Evaluation, Preclinical; Pharmaceutical Vehicles; Toxicity Tests
PubMed: 17132609
DOI: 10.1080/10915810600961531 -
Journal of the American Association For... Sep 2011Administration of substances to laboratory animals requires careful consideration and planning to optimize delivery of the agent to the animal while minimizing potential...
Administration of substances to laboratory animals requires careful consideration and planning to optimize delivery of the agent to the animal while minimizing potential adverse experiences from the procedure. For all species, many different routes are available for administration of substances. The research team and IACUC members should be aware of reasons for selecting specific routes and of training and competency necessary for personnel to use these routes effectively. Once a route is selected, issues such as volume of administration, site of delivery, pH of the substance, and other factors must be considered to refine the technique. Inadequate training or inattention to detail during this aspect of a study may result in unintentional adverse effects on experimental animals and confounded results.
Topics: Animal Care Committees; Animal Welfare; Animals; Animals, Laboratory; Drug Administration Routes; Laboratory Animal Science; Research Design
PubMed: 22330705
DOI: No ID Found -
Yakugaku Zasshi : Journal of the... Aug 2003Development of drug delivery systems to achieve site-specific delivery or prolonged retention in the circulation has attracted attention, because new types of drugs are... (Review)
Review
Development of drug delivery systems to achieve site-specific delivery or prolonged retention in the circulation has attracted attention, because new types of drugs are expected to be created with advances in life science and biotechnology such as the Human Genome Project. We have tried to develop a new administration route for drug targeting to the liver, since drug administration by the intravenous and oral routes makes it difficult to achieve a local site of action in the liver. Although direct application to the liver surface should result in local drug distribution, drug absorption from the liver surface has not been reported in the literature. Therefore we analyzed the absorption mechanism of several organic anions and dextrans with different molecular weights as model drugs, after application to the rat liver surface in vivo, employing a cylindrical diffusion cell. Every compound appeared gradually in the plasma, followed by excretion into the bile and/or urine, indicating the possibility of drug absorption from the liver surface. A specific transport system might not be involved in the absorption process from the liver surface, because the effect of dose and transport inhibitors on the absorption was not recognized. In addition, molecular weight was found to be a determining factor in absorption from the liver surface. The targeting efficacy was considerably enhanced by application to the liver surface, as compared with intravenous administration. Moreover, we have identified important physicochemical and pharmaceutical factors determining the absorption rate of a drug from the liver surface for clinical use. Consequently, drug application to the liver surface could improve availability in the desired site of a new drug such as bioactive compounds and genomic medicines, by combination with appropriate chemical and pharmaceutical formulation modifications.
Topics: Animals; Binding Sites; Chemical Phenomena; Chemistry, Physical; Drug Administration Routes; Drug Delivery Systems; Drug Design; Humans; Liver; Rats; Tissue Distribution
PubMed: 12931664
DOI: 10.1248/yakushi.123.681