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Drugs in R&D Sep 2023The benefit of exogenous melatonin is based on its bioavailability, which depends on the galenic form, the route of administration, the dosage, and the individual... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The benefit of exogenous melatonin is based on its bioavailability, which depends on the galenic form, the route of administration, the dosage, and the individual absorption and rate of hepatic metabolism.
OBJECTIVE
The objective of this study is to investigate the bioavailability of melatonin after administration of an oral prolonged-release tablet (PR form) and an immediate-release sublingual spray (IR form). The main metabolite of melatonin, 6-sulfatoxymelatonin (6-SMT), was also measured, which has not been done in previous studies. Its determination is important as an index of the hepatic transformation of melatonin.
METHODS
In this single-center, open-label, randomized, crossover study, 14 healthy male volunteers received one tablet of the PR form (1.9 mg melatonin) or two sprays of the IR form (1 mg melatonin) during two visits separated by a washout period. Blood samples were collected over 7 and 9 h for the IR and PR form, respectively, to determine the main pharmacokinetic parameters.
RESULTS
The observed kinetics were consistent with those expected for immediate and prolonged-release forms. Pulverization of the spray resulted in an early, high plasma melatonin peak (C: 2332 ± 950 pg/mL; T: 23.3 ± 6.5 min), whereas tablet intake produced a lower peak (C: 1151 ± 565 pg/mL; T: 64.2 ± 44.2 min; p < 0.001 for comparison of C and T) followed by a plasma melatonin plateau and a more prolonged decay over time. Plasma melatonin/6-SMT AUC ratio was 0.09 for the PR form and 0.16 for the IR form. Both galenic forms were well tolerated.
CONCLUSIONS
The results suggest that the galenic forms containing melatonin assessed in this study are suitable for the treatment of certain sleep disorders such as sleep onset delay and transient nocturnal awakenings for the IR form and insomnia for the PR form.
TRIAL REGISTRY
Registration number: NCT04574141.
Topics: Humans; Male; Biological Availability; Cross-Over Studies; Melatonin; Tablets; Volunteers; Administration, Oral; Area Under Curve
PubMed: 37438493
DOI: 10.1007/s40268-023-00431-9 -
Journal of Traditional Chinese Medicine... Oct 2023In the study of the mechanism of wound healing after anal fistula surgery, how to scientifically and efficiently promote wound healing is of great significance. At...
In the study of the mechanism of wound healing after anal fistula surgery, how to scientifically and efficiently promote wound healing is of great significance. At present, modern medical treatment of wounds after anal fistula surgery mostly focuses on physical therapy intervention, new wound dressing and packing, and external application of growth factors. However, these therapies have many problems, and there is still no consensus on their clinical use. Traditional Chinese Medicine (TCM) has several methods to promote wound healing, such as oral administration, rubbing, and fumigation, which have a long history and obvious efficacy, but research in this area is relatively scattered and lacks classification and summarizing. Therefore, this paper analyzes and summarizes the existing research on TCM for promotion of wound healing after anal fistula surgery, carries out targeted analyses according to different clinical syndromes and treatment methods, and analyzes the defects in current research and anticipates future research trends in order to provide theoretical support for the advantages of TCM in promoting wound healing after anal fistula surgery.
Topics: Humans; Medicine, Chinese Traditional; Administration, Oral; Wound Healing; Rectal Fistula
PubMed: 37679994
DOI: 10.19852/j.cnki.jtcm.20230630.002 -
Veterinary Anaesthesia and Analgesia Nov 2023To determine the pharmacokinetics and bioavailability of meloxicam following intravenous (IV), intramuscular (IM), and oral administrations at a dose of 1.0 mg kg in...
OBJECTIVE
To determine the pharmacokinetics and bioavailability of meloxicam following intravenous (IV), intramuscular (IM), and oral administrations at a dose of 1.0 mg kg in Pekin ducks.
STUDY DESIGN
Randomized experimental trial.
ANIMALS
A total of 18 clinically healthy male Pekin ducks.
METHODS
Pekin ducks were randomly assigned to three groups of six ducks: IV, IM and oral. Meloxicam (1.0 mg kg) was administered to each Pekin duck. A non-compartmental analysis was used to evaluate pharmacokinetic parameters.
RESULTS
No local or systemic adverse effects were observed in any bird. Meloxicam was detected in the plasma up to 120 hours following IV, IM or oral administration. The elimination half-life of the IV route was slightly shorter than that of the IM and oral routes (p < 0.05). Following IV administration, volume of distribution at steady state and total clearance were 133.17 mL kg and 6.68 mL kg hour, respectively. The mean absorption time was 2.29 hours for IM and 1.13 hours for oral route. There were significant differences between IM and oral administration for the peak plasma concentration (C), time to reach C and bioavailability (p < 0.05).
CONCLUSIONS AND CLINICAL RELEVANCE
Meloxicam showed long elimination half-life and high bioavailability following IM and oral administration. Meloxicam in Pekin ducks provided the effective therapeutic concentration indicated in other species for up to 48 hours. However, there is a need to determine the clinical efficacy of meloxicam in Pekin ducks.
Topics: Male; Animals; Meloxicam; Ducks; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Area Under Curve; Half-Life; Injections, Intravenous; Administration, Oral; Injections, Intramuscular; Administration, Intravenous
PubMed: 37620232
DOI: 10.1016/j.vaa.2023.07.007 -
International Journal of Nanomedicine 2024Nanosuspensions have garnered recent attention as a promising strategy for mitigating the bioavailability challenges of hydrophobic drugs, particularly those... (Review)
Review
Nanosuspensions have garnered recent attention as a promising strategy for mitigating the bioavailability challenges of hydrophobic drugs, particularly those characterized by poor solubility in both aqueous and organic environments. Addressing solubility issues associated with poorly water-soluble drugs has largely resolved the need to enhance drug absorption and bioavailability. As mucosal formulations and topical administration progress in the future, nanosuspension drug delivery, straightforward formulation techniques, and versatile applications will continue to be subjects of interest. Nanosuspensions have undergone extensive scrutiny in preparation for topical applications, encompassing ocular, pulmonary, and dermal usage. Among the numerous methods aimed at improving cutaneous application, nanocrystals represent a relatively recent yet profoundly intriguing approach. Despite the increasing availability of various nanosuspension products, primarily designed for oral administration, only a limited number of studies have explored skin permeability and drug accumulation in the context of nanosuspensions. Nevertheless, the scant published research unequivocally underscores the potential of this approach for enhancing cutaneous bioavailability, particularly for active ingredients with low to medium solubility. Nanocrystals exhibit increased skin adhesiveness in addition to heightened saturation solubility and dissolution rate, thereby augmenting cutaneous distribution. The article provides a comprehensive overview of nanosuspensions for topical application. The methodology employed is robust, with a well-defined experimental design; however, the limited sample size raises concerns about the generalizability of the findings. While the results demonstrate promising outcomes in terms of enhanced drug delivery, the discussion falls short of addressing certain limitations. Additionally, the references largely focus on recent studies, but a more diverse inclusion of historical perspectives could offer a more holistic view of the subject.
Topics: Humans; Suspensions; Drug Delivery Systems; Biological Availability; Nanoparticles; Administration, Oral; Solubility; Particle Size
PubMed: 38293608
DOI: 10.2147/IJN.S447429 -
Biomaterials Advances Oct 2023The upsurge of bacterial resistance to conventional antibiotics turned a well-recognized public health threat. The need of developing new biomaterials of effective...
The upsurge of bacterial resistance to conventional antibiotics turned a well-recognized public health threat. The need of developing new biomaterials of effective practical use in order to tackle bacterial resistance became urgent. In this study, a submicrometric bioparticle of known antibacterial activity was produced in powder form with suitable texture and appealing characteristics for effective oral administration. Through complex coacervating a natural-source antimicrobial polypeptide with chitosan-N-arginine and alginate, the bioactive polypeptide was physically incorporated to the bioparticle whose structure positively responds to the pH variations found in gastrointestinal tract. The powder formulation presented high palatability that was evaluated using fish as in vivo animal model. A thorough survey of the fish intestinal tissues, following a systematic oral administration, revealed high penetration potential of the biomaterial through epithelial cells and deeper intestine layers. Despite, no cytotoxic effect was observed in analyzing the tissues through different histology methods. The absence of intestinal damage was corroborated by immune histochemistry, being the integrity of epithelial motor myosin Vb and related traffic proteins preserved. Hematology further endorsed absence of toxicity in blood cells whose morphology was evaluated in detail. The study evidenced the applicability potential of a new biomaterial of appealing and safe oral administration of antibacterial polypeptide.
Topics: Peptides; Anti-Bacterial Agents; Administration, Oral; Powders; Catfishes; Animals; Particle Size; Hydrogen-Ion Concentration
PubMed: 37352744
DOI: 10.1016/j.bioadv.2023.213525 -
Pharmaceutical Biology Dec 2023Attempts are ongoing to develop medications to fight against the COVID-19 pandemic. Our previous study revealed the anti-SARS-CoV-2 activity of fingerroot [ (L.) Mansf....
CONTEXT
Attempts are ongoing to develop medications to fight against the COVID-19 pandemic. Our previous study revealed the anti-SARS-CoV-2 activity of fingerroot [ (L.) Mansf. (Zingiberaceae)] and its phytochemical, panduratin A.
OBJECTIVE
To investigate the pharmacokinetic profiles of panduratin A as a pure compound and in a fingerroot extract formulation in beagle dogs.
MATERIALS AND METHODS
A total of 12 healthy dogs were randomly divided into three groups, a single dose of 1 mg/kg panduratin A by intravenous and multiple doses of 5 and 10 mg/kg panduratin A fingerroot extract formulation by oral administration for seven consecutive days. The plasma concentration of panduratin A was determined by LCMS.
RESULTS
The peak concentrations of a single dose of 5 and 10 mg/kg panduratin A fingerroot extract formulation were 12,416 ± 2,326 and 26,319 ± 8,221 µg/L, respectively. Increasing the oral dose of fingerroot extract formulation, equivalent to panduratin A 5-10 mg/kg, showed dose proportionality, with an approximately 2-fold increase in and AUC. The absolute oral bioavailability of panduratin A in the fingerroot extract formulation was approximately 7-9%. The majority of panduratin A was biotransformed into several products oxidation and glucuronidation, and predominantly excreted the faecal route.
CONCLUSION
The oral formulation of fingerroot extract was safe in beagle dogs, and increasing dose showed dose proportionality in terms of the systemic exposure of panduratin A. This information will support the phytopharmaceutical product development of fingerroot extract against the COVID-19 pandemic.
Topics: Dogs; Animals; Humans; Biological Availability; Pandemics; COVID-19; Zingiberaceae; Administration, Oral; Plant Extracts; Metabolic Networks and Pathways
PubMed: 36994846
DOI: 10.1080/13880209.2023.2190777 -
International Journal of Biological... Jul 2023Chitosan is an abundant natural cationic polysaccharide with excellent biodegradability, bioadhesion, and biocompatibility. Chitosan is extensively researched for... (Review)
Review
Chitosan is an abundant natural cationic polysaccharide with excellent biodegradability, bioadhesion, and biocompatibility. Chitosan is extensively researched for various particulate oral insulin drug delivery systems. Oral insulin is economically efficient and more convenient than injections, with greater patient compliance. Electrostatic ionic interaction between cationic chitosan and anionic polymer or insulin leads to the formation of spontaneously self-assembled nanoparticles. This simple technique attracted many researchers as it can be carried out quickly in mild conditions without harmful solvents, such as surfactants or chemical cross-linkers that might degrade the insulin structure. The formulated chitosan nanoparticles help to protect the core insulin from enzymatic degradation in the digestive system and improve paracellular intestinal uptake from the enterocytes due to mucoadhesion and reversible tight junction opening. Moreover, functionalized chitosan nanoparticles create newer avenues for targeted and prolonged delivery. This review focuses on modified chitosan-insulin nanoparticles and their implications on oral insulin delivery. Dependent variables and their optimal concentration ranges used in self-assembly techniques for chitosan-insulin nanoparticular synthesis are summarized. This review provides a comprehensive guide to fine-tune the essential factors to formulate stable insulin-chitosan nanoparticles using mild ionic interactions.
Topics: Humans; Insulin; Chitosan; Drug Carriers; Drug Delivery Systems; Nanoparticles; Administration, Oral
PubMed: 37263321
DOI: 10.1016/j.ijbiomac.2023.125125 -
Clinical Microbiology and Infection :... Sep 2023
Topics: Humans; Administration, Intravenous; Anti-Bacterial Agents; Communicable Diseases; Administration, Oral; Infusions, Intravenous
PubMed: 37353077
DOI: 10.1016/j.cmi.2023.06.021 -
Journal of Nanobiotechnology Aug 2023Oral administration is preferred over other drug delivery methods due to its safety, high patient compliance, ease of ingestion without discomfort, and tolerance of a... (Review)
Review
Oral administration is preferred over other drug delivery methods due to its safety, high patient compliance, ease of ingestion without discomfort, and tolerance of a wide range of medications. However, oral drug delivery is limited by the poor oral bioavailability of many drugs, caused by extreme conditions and absorption challenges in the gastrointestinal tract. This review thoroughly discusses the targeted drug vehicles to the intestinal lymphatic system (ILS). It explores the structure and physiological barriers of the ILS, highlighting its significance in dietary lipid and medication absorption and transport. The review presents various approaches to targeting the ILS using spatially precise vehicles, aiming to enhance bioavailability, achieve targeted delivery, and reduce first-pass metabolism with serve in clinic. Furthermore, the review outlines several methods for leveraging these vehicles to open the ILS window, paving the way for potential clinical applications in cancer treatment and oral vaccine delivery. By focusing on targeted drug vehicles to the ILS, this article emphasizes the critical role of these strategies in improving therapeutic efficacy and patient outcomes. Overall, this article emphasizes the critical role of targeted drug vehicles to the ILS and the potential impact of these strategies on improving therapeutic efficacy and patient outcomes.
Topics: Humans; Pharmaceutical Preparations; Lymphatic System; Gastrointestinal Tract; Drug Delivery Systems; Biological Availability; Administration, Oral
PubMed: 37559085
DOI: 10.1186/s12951-023-01991-3 -
Journal of Controlled Release :... Aug 2023Oral administration is a convenient administration route for gastrointestinal disease therapy with good patient compliance. But the nonspecific distribution of the oral... (Review)
Review
Oral administration is a convenient administration route for gastrointestinal disease therapy with good patient compliance. But the nonspecific distribution of the oral drugs may cause serious side effects. In recent years, oral drug delivery systems (ODDS) have been applied to deliver the drugs to the gastrointestinal disease sites with decreased side effects. However, the delivery efficiency of ODDS is tremendously limited by physiological barriers in the gastrointestinal sites, such as the long and complex gastrointestinal tract, mucus layer, and epithelial barrier. Micro/nanomotors (MNMs) are micro/nanoscale devices that transfer various energy sources into autonomous motion. The outstanding motion characteristics of MNMs inspired the development of targeted drug delivery, especially the oral drug delivery. However, a comprehensive review of oral MNMs for the gastrointestinal diseases therapy is still lacking. Herein, the physiological barriers of ODDS were comprehensively reviewed. Afterward, the applications of MNMs in ODDS for overcoming the physiological barriers in the past 5 years were highlighted. Finally, future perspectives and challenges of MNMs in ODDS are discussed as well. This review will provide inspiration and direction of MNMs for the therapy of gastrointestinal diseases, pushing forward the clinical application of MNMs in oral drug delivery.
Topics: Humans; Nanotechnology; Drug Delivery Systems; Gastrointestinal Tract; Administration, Oral
PubMed: 37429360
DOI: 10.1016/j.jconrel.2023.07.005