scholarly journals Long-Circulating Hyaluronan-Based Nanohydrogels as Carriers of Hydrophobic Drugs

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 213 ◽  
Author(s):  
Chiara Di Meo ◽  
Mayte Martínez-Martínez ◽  
Tommasina Coviello ◽  
Marival Bermejo ◽  
Virginia Merino ◽  
...  
Keyword(s):  
Drug Administration ◽  
Intravenous Administration ◽  
Therapeutic Agents ◽  
Pharmacokinetic Parameters ◽  
Hydrophobic Drugs ◽  
Natural Polymers ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Model Drug ◽  
High Doses

Nanohydrogels based on natural polymers, such as polysaccharides, are gaining interest as vehicles for therapeutic agents, as they can modify the pharmacokinetics and pharmacodynamics of the carried drugs. In this work, hyaluronan-riboflavin nanohydrogels were tested in vivo in healthy rats highlighting their lack of toxicity, even at high doses, and their different biodistribution with respect to that of native hyaluronan. They were also exploited as carriers of a hydrophobic model drug, the anti-inflammatory piroxicam, that was physically embedded within the nanohydrogels by an autoclave treatment. The nanoformulation was tested by intravenous administration showing an improvement of the pharmacokinetic parameters of the molecule. The obtained results indicate that hyaluronan-based self-assembled nanohydrogels are suitable systems for low-soluble drug administration, by increasing the dose as well as the circulation time of poorly available therapeutic agents.

scholarly journals Polymyxins Nebulization over Intravenous Injection: Pharmacokinetics and Pharmacodynamics-Based Therapeutic Evaluation

2019 ◽  
pp. 1-10
Author(s):  
Md. Jahidul Hasan
Keyword(s):  
Respiratory Tract ◽  
Adverse Drug Reactions ◽  
Intravenous Administration ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Drug Reactions ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Gram Negative ◽  
Tract Infections

Polymyxins are the last line potential antibiotics against multi-drug resistant gram-negative bacteria and consist of two sister antibiotics: Polymyxin B and colistin (polymyxin E). Intravenous use of polymyxins was started from a long ago in the treatment of serious gram-negative infections and once their uses were restricted due to potential adverse drug reactions, such as nephrotoxicity and neurotoxicity. Lack of in vivo clinical studies on polymyxins mostly, in human body makes the pharmacokinetics and pharmacodynamics of polymyxin B and colistin unclear in many aspects, such as the distribution of polymyxins in different compartments of lung. The nebulization of polymyxins is practicing very limitedly and lack of clinical evidence has not justified this administration technique yet properly to date. The main objective of this review study was to evaluate the pharmacokinetic and pharmacodynamic properties of intravenous and nebulized polymyxins and the related therapeutic potentialities. Aerosolized polymyxins directly administered to the respiratory tract was found with higher drug concentration in different subcompartments of lungs than the intravenous administration and sustainably meets the minimum inhibitory concentration locally with superior bactericidal properties in respiratory tract infections. In contrast, intravenous administration of polymyxins shows similar anti-infective superiority in other organs, such as blood, urinary tract etc. So, during this alarming situation of rapidly emerging multidrug-resistant organisms in human communities, therapeutic administration techniques of last resort polymyxins should be clinically evidence-based for achieving optimum therapeutic outcomes with minimum chance of adverse drug reactions.  

scholarly journals Ultrasound Mediated Delivery of Quantum Dots from a Capsule Endoscope to the Gastrointestinal Wall

2020 ◽  
Author(s):  
Fraser Stewart ◽  
Gerard Cummins ◽  
Mihnea V. Turcanu ◽  
Benjamin F. Cox ◽  
Alan Prescott ◽  
...  
Keyword(s):  
Small Intestine ◽  
Oral Delivery ◽  
Focused Ultrasound ◽  
Living Organism ◽  
Therapeutic Agents ◽  
Biologic Drugs ◽  
Fluorescent Markers ◽  
Capsule Endoscopes ◽  
Model Drug

AbstractBiologic drugs, defined as therapeutic agents produced from or containing components of a living organism, are of growing importance to the pharmaceutical industry. Though oral delivery of medicine is convenient, biologics require invasive injections because of their poor bioavailability via oral routes. Delivery of biologics to the small intestine using electronic delivery with devices that are similar to capsule endoscopes is a promising means of overcoming this limitation and does not require reformulation of the therapeutic agent. The efficacy of such capsule devices for drug delivery could be further improved by increasing the permeability of the intestinal tract lining with an integrated ultrasound transducer to increase uptake. This paper describes a novel proof of concept capsule device capable of electronic application of focused ultrasound and delivery of therapeutic agents. Fluorescent markers, which were chosen as a model drug, were used to demonstrate in-vivo delivery in the porcine small intestine with this capsule. We show that the fluorescent markers can penetrate the mucus layer of the small intestine at low acoustic powers when combining microbubbles with focussed ultrasound. These findings suggest that the use of focused ultrasound together with microbubbles could play a role in the oral delivery of biologic therapeutics.

Effects of Parecoxib, a Parenteral COX-2-specific Inhibitor, on the Pharmacokinetics and Pharmacodynamics of Propofol

2002 ◽  
Vol 96 (1) ◽  
pp. 88-95 ◽  
Author(s):  
Andra Ibrahim ◽  
Sang Park ◽  
Jennifer Feldman ◽  
Aziz Karim ◽  
Evan D. Kharasch
Keyword(s):  
Visual Analog Scale ◽  
Bispectral Index ◽  
Specific Inhibitor ◽  
Pharmacokinetic Parameters ◽  
Digit Symbol ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Analog Scale ◽  
Clinical Endpoints ◽  
Symbol Substitution

Background Parecoxib, a cyclooxygenase-2-specific inhibitor with intended perioperative analgesic and antiinflammatory use, is a parenterally administered inactive prodrug undergoing rapid hydrolysis in vivo to the active cyclooxygenase-2 inhibitor valdecoxib. Both parecoxib and valdecoxib inhibit human cytochrome P450 2C9 (CYP2C9) activity in vitro. Thus, a potential exists for in vivo interactions with other CYP2C9 substrates, including propofol. This investigation determined the influence of parecoxib on the pharmacokinetics and pharmacodynamics of bolus dose propofol in human volunteers. Methods This was a randomized, balanced crossover, placebo-controlled, double-blind, clinical investigation. Twelve healthy 21- to 37-yr-old subjects were studied after providing institutional review board-approved written informed consent. Each subject received a 2-mg/kg intravenous propofol bolus 1 h after placebo (control) or 40 mg intravenous parecoxib on two occasions. Venous concentrations of propofol, parecoxib, and parecoxib metabolites were determined by mass spectrometry. Pharmacokinetic parameters were determined by noncompartmental analysis. Pharmacodynamic measurements included clinical endpoints, cognitive function (memory, Digit-Symbol Substitution Tests), subjective self-assessment of recovery (Visual Analog Scale) performed at baseline, 15, 30, 60 min after propofol, and sedation depth measured by Bispectral Index. Results Propofol plasma concentrations were similar between placebo- and parecoxib-treated subjects. No significant differences were found in pharmacokinetic parameters (Cmax, clearance, elimination half-life, volume of distribution) or pharmacodynamic parameters (clinical endpoints [times to: loss of consciousness, apnea, return of response to voice], Bispectral Index scores, Digit-Symbol Substitution Test scores, memory, Visual Analog Scale scores, propofol EC(50)). Conclusions Single-bolus parecoxib, in doses to be used perioperatively, does not alter the disposition or the magnitude or time course of clinical effects of bolus propofol. Effects on a propofol infusion were not evaluated.

Development of An Antidiabetic Phytocomposite Loaded Phytoceutical Formulation, Its Quality Control and Pharmacokinetic Studies and Establishing In Vitro- In Vivo Correlation

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
De Baishakhi ◽  
Bhandari Koushik ◽  
Katakam Prakash ◽  
Adiki Shanta ◽  
Mitra Analava
Keyword(s):  
Rat Plasma ◽  
Angle Of Repose ◽  
Fickian Diffusion ◽  
Core Material ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Natural Polymers ◽  
Gum Karaya

This study reports the development of solid oral phytoceutical formulations with Phytocomposite (PHC), an antidiabetic poly herbal preparation as the active core material. Spherical, monolithic PHC microspheres of size range (10 -100 µm) were obtained with Hausner ratio, Carr’s index and angle of repose of 1.141± 0.010, 12.418±0.769 and 25.17±0.96 respectively. Encapsulation efficiency amongst different batches (F1-F5) ranged from 96.8- 100.7, with 99% release profile up to 12h. Conventional and sustained release tablets were prepared by direct compression and compatibility amongst polymers and the PHC checked by FTIR studies. Natural polymers viz. gum kondagogu, gum karaya, Aegle marmelos gum were used as release retardant. Optimized batch of conventional tablets (F6) showed 99.8 % release in 35 min and optimized batch of PHC-SR tablets (F12) showed 99.9% release at 12th hr, both followed zero order kinetics and non-Fickian diffusion. These optimized formulations were subjected to stability studies and the similarity factors (f2) of the conventional and SR tablets were 88.75 and 66.76 respectively. Pharmacokinetic parameters of three formulations in rat plasma were analyzed by PK Solver 2.0. In vitro-in vivo correlation (IVIVC) of three different formulations showed Level A correlation in all cases.

Drug Delivery, Monitoring, and Interactions

2018 ◽  
Author(s):  
Eelco F. M. Wijdicks ◽  
Sarah L. Clark
Keyword(s):  
Drug Delivery ◽  
Drug Interactions ◽  
Drug Administration ◽  
Clinical Relevance ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Drug Administration Routes ◽  
Administration Routes ◽  
Main Components ◽  
Drug Errors

This chapter outlines the typical pathway of an administered drug and the factors that affect it. The main components that determine a drug’s pharmacokinetics and pharmacodynamics are discussed. Issues important for the physician such as Pharmacokinetic parameters, drug administration routes, and principles of drug interactions are highlighted. Problems with inadvertently holding home or maintenance medications and other drug errors are outlined. Pharmacogenomics and its emerging clinical relevance is introduced.

Koffein: hagyományos és új terápiás indikációk, valamint felhasználás dermatológiai modellvegyületként

2018 ◽  
Vol 159 (10) ◽  
pp. 384-390 ◽  
Author(s):  
Luca Bors ◽  
Ágnes Bajza ◽  
Dorottya Kocsis ◽  
Franciska Erdő
Keyword(s):  
Coffee Consumption ◽  
Skin Penetration ◽  
Antioxidant Property ◽  
Pharmacological Effects ◽  
Coffee Drinking ◽  
Beneficial Effects ◽  
15Th Century ◽  
Model Drug ◽  
High Doses

Abstract: Coffee consumption had already been described in the 15th century. The spreading of coffee drinking was not only a consequence of its delicious aromatic taste, but also of its pharmacological effects, especially due to its caffeine content. In this review, the mechanisms behind its complex stimulatory effects and the latest studies on the possible new therapeutic indications of caffeine are summarized. Several papers reported the neuroprotective (in Alzheimer’s and Parkinson’s disease) and hepatoprotective profiles of caffeine, and we show the most promising new results about its preventive properties in dermal malignancies. These findings were described both in cell cultures and in vivo. The application of caffeine and coffee in cosmetology and dermatological products is based on their antioxidant property and on the above-mentioned beneficial effects. Caffeine is also presented here as a dermatological model drug due to its hydrophilic profile. It can be used for designing and comparing different novel drug formulations, although beside the transcellular route, the follicular and transappendageal pathways play also important roles in its skin penetration. Taken together, caffeine molecule has many recently discovered beneficial pharmacological effects, but one should be careful with its excessive consumption. It can result in several adverse events if overdosed and in case of regular intake of high doses, after abandonment, withdrawal symptoms may appear. Orv Hetil. 2018; 159(10): 384–390.

Scintigraphic Detection of Experimental Myocardial Infarction with 99mTc-2,3-Dimercaptosuccinic Acid

1984 ◽  
Vol 23 (06) ◽  
pp. 317-319
Author(s):  
J. Novák ◽  
Y. Mazurová ◽  
J. Kubíček ◽  
J. Yižd’a ◽  
P. Kafka ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Intravenous Administration ◽  
Experimental Myocardial Infarction ◽  
Myocardial Infarctions ◽  
Clinical Use ◽  
Scintigraphic Imaging ◽  
Tissue Samples ◽  
Scintigraphic Finding

SummaryAcute myocardial infarctions were produced by ligature of the left frontal descending coronary artery in 9 dogs. The possibility of scintigraphic imaging with 99mTc-DMSA 4 hrs after intravenous administration was studied. The infarctions were 4, 24 and 48 hrs old. The in vivo scan was positive in only one dog with a 4-hr old infarction. The in vivo scans were confirmed by the analysis of the radioactivity in tissue samples. The accumulation of the radiopharmaceutical increased slightly in 48-hr old lesions; however, this increase was not sufficient for a positive scintigraphic finding. Thus, we do not recommend 99mTc-DMSA for clinical use in acute lesions.

In Vivo Effect of Suloctidil as an Antiplatelet Agent

1979 ◽  
Vol 41 (03) ◽  
pp. 465-474 ◽  
Author(s):  
Marcia R Stelzer ◽  
Thomas S Burns ◽  
Robert N Saunders
Keyword(s):  
Ex Vivo ◽  
Antiplatelet Agent ◽  
Ratio Method ◽  
Platelet Aggregate ◽  
Permanent Effect ◽  
Platelet Aggregates ◽  
5 Ht Uptake ◽  
High Doses

SummaryThe relationship between the effects of suloctidil in vivo as an antiplatelet agent and in vitro as a modifier of platelet serotonin (5-HT) parameters was investigated. Suloctidil was found to be effective in reducing platelet aggregates formation in the retired breeder rat as determined using the platelet aggregate ratio method (PAR) with an ED50 of 16.1 mg/kg 24 hours post administration. In contrast to the hypothesis that 5-HT depletion is involved in the anti-aggregatory mechanism of suloctidil, no correlation was found between platelet 5- HT content and this antiplatelet activity. Reduction of platelet 5-HT content required multiple injections of high doses (100 mg/kg/day) of suloctidil. Suloctidil administration for 8 days at 100 mg/kg/day, which lowered platelet 5-HT content by 50%, resulted in no permanent effect on ex vivo platelet 5-HT uptake or thrombin-induced release, nor alteration in the plasma 5-HT level. However, these platelets exhibited a short-lived, significant increase in percent leakage of 5-HT after 30 minutes of incubation. Therefore, suloctidil treatment at high doses may with time result in platelet 5-HT depletion, however this effect is probably not related to the primary anti-aggregatory activity of the drug.

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