scholarly journals In Vitro and In Vivo Activities of the Novel Azole Antifungal Agent R126638

2004 ◽  
Vol 48 (2) ◽  
pp. 388-391 ◽  
Author(s):  
F. Odds ◽  
J. Ausma ◽  
F. Van Gerven ◽  
F. Woestenborghs ◽  
L. Meerpoel ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Side Effects ◽  
Guinea Pig ◽  
Antifungal Agent ◽  
Lower Risk ◽  
The Novel ◽  
Duration Of Treatment ◽  
Effective Doses

ABSTRACT R126638 is a new triazole agent with potent antifungal activity in vitro against various dermatophytes, Candida spp., and Malassezia spp. Its activity against Malassezia spp. in vitro was superior to that of ketoconazole, the agent currently used for the treatment of Malassezia-related infections. R126638 showed activity comparable to or lower than that of itraconazole against dermatophytes in vitro; however, in guinea pig models of dermatophyte infections, R126638 given orally consistently showed antifungal activity superior to that of itraconazole, with 50% effective doses (ED50s) three- to more than eightfold lower than those of itraconazole, depending on the time of initiation and the duration of treatment. The ED50 of R126638 in a mouse dermatophytosis model was more than fivefold lower than that of itraconazole. These data indicate that if the effects of R126638 seen when it is used to treat animals can be extrapolated to humans, the novel compound would be expected to show effects at doses lower than those of existing drugs and, hence, present a lower risk for side effects.

Oleic Acid Vesicles as a new Approach for Transdermal Delivery of Econazole Nitrate: Development, Characterization, and In-vivo Evaluation in Wistar rats

2020 ◽  
Vol 15 ◽  
Author(s):  
Shivani Verma ◽  
Puneet Utreja
Keyword(s):  
Oleic Acid ◽  
Antifungal Activity ◽  
Side Effects ◽  
Fungal Infection ◽  
Wistar Rats ◽  
Skin Permeation ◽  
Cutaneous Candidiasis ◽  
Econazole Nitrate

Background:: Cutaneous candidiasis is a deep-seated skin fungal infection that is most commonly observed in immunocompromised patients. This fungal infection is conventionally treated with various formulations like gels and creams which are having different side effects and least therapeutic efficacy. Hence, it becomes necessary to develop a novel carrier system for the treatment of this deep-seated skin fungal infection. Econazole nitrate is the most widely used antifungal for the treatment of cutaneous candidiasis, therefore, in present research work we developed and evaluated econazole nitrate loaded oleic acid vesicles for treatment of cutaneous candidiasis through transdermal route. Methods:: Econazole nitrate loaded oleic acid vesicles were prepared by thin-film hydration and characterized for drug entrapment, vesicle size, zeta potential, polydispersity index (PDI), Fourier Transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) analysis. Furthermore, the oleic acid vesicular gel was evaluated for ex-vivo skin permeation/retention and in-vitro and in-vivo antifungal activity in Wistar rats. Results:: Econazole nitrate loaded oleic acid vesicles showed high encapsulation of drug (74.76 ± 3.0%), acceptable size (373.4 ± 2.9 nm), and colloidal characteristics (PDI = 0.231 ± 0.078, zeta potential = -13.27 ± 0.80 mV). The oleic acid vesicular gel showed high skin permeation (Transdermal flux = 61.98 ± 2.45 μg/cm2/h), skin retention (35.90 ± 2.06%), in-vitro, and in-vivo antifungal activity compared to marketed cream (EcodermR) of econazole nitrate for a prolonged period of time (4 days). Conclusion:: Developed econazole nitrate loaded oleic acid vesicles could be used effectively in the treatment of cutaneous candidiasis with minimization of side effects of econazole nitrate with increased therapeutic efficacy.

scholarly journals In Vitro and In Vivo Activities of CS-758 (R-120758), a New Triazole Antifungal Agent

2002 ◽  
Vol 46 (2) ◽  
pp. 367-370 ◽  
Author(s):  
Yasuki Kamai ◽  
Tamako Harasaki ◽  
Takashi Fukuoka ◽  
Satoshi Ohya ◽  
Katsuhisa Uchida ◽  
...  
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Antifungal Agent ◽  
The Other ◽  
In Vitro Activity ◽  
Effective Doses ◽  
Low Levels ◽  
Systemic Infections

ABSTRACT The activity of CS-758 (R-120758), a new triazole antifungal agent, was evaluated and compared with those of fluconazole, itraconazole, and amphotericin B in vitro and with those of fluconazole and itraconazole in vivo. CS-758 exhibited potent in vitro activity against clinically important fungi. The activity of CS-758 against Candida spp. was superior to that of fluconazole and comparable or superior to those of itraconazole and amphotericin B. CS-758 retained potent activity against Candida albicans strains with low levels of susceptibility to fluconazole (fluconazole MIC, 4 to 32 μg/ml). Against Aspergillus spp. and Cryptococcus neoformans, the activity of CS-758 was at least fourfold superior to those of the other drugs tested. CS-758 also exhibited potent in vivo activity against murine systemic infections caused by C. albicans, C. neoformans, Aspergillus fumigatus, and Aspergillus flavus. The 50% effective doses against these infections were 0.41 to 5.0 mg/kg of body weight. These results suggest that CS-758 may be useful in the treatment of candidiasis, cryptococcosis, and aspergillosis.

scholarly journals In Vitro and In Vivo Activities of Novel 6-Methylidene Penems as β-Lactamase Inhibitors

2004 ◽  
Vol 48 (12) ◽  
pp. 4589-4596 ◽  
Author(s):  
William J. Weiss ◽  
Peter J. Petersen ◽  
Timothy M. Murphy ◽  
LuAnna Tardio ◽  
Youjun Yang ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Therapeutic Agents ◽  
Pharmacokinetic Analysis ◽  
The Novel ◽  
Class A ◽  
Lactam Antibiotic ◽  
Effective Doses ◽  
Volumes Of Distribution

ABSTRACT Novel penem molecules with heterocycle substitutions at the 6 position via a methylidene linkage were investigated for their activities and efficacy as β-lactamase inhibitors. The concentrations of these molecules that resulted in 50% inhibition of enzyme activity were 0.4 to 3.1 nM for the TEM-1 enzyme, 7.8 to 72 nM for Imi-1, 1.5 to 4.8 nM for AmpC, and 14 to 260 nM for a CcrA metalloenzyme. All the inhibitors were more stable than imipenem against hydrolysis by hog and human dehydropeptidases. Piperacillin was combined with a constant 4-μg/ml concentration of each inhibitor for MIC determinations. The combinations reduced piperacillin MICs by 2- to 32-fold for extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae strains. The MICs for piperacillin-resistant (MIC of piperacillin, >64 μg/ml) strains of Enterobacter spp., Citrobacter spp., and Serratia spp. were reduced to the level of susceptibility (MIC of piperacillin, ≤16 μg/ml) when the drug was combined with 4, 2, or 1 μg of these penem inhibitors/ml. Protection against acute lethal bacterial infections with class A and C β-lactamase- and ESBL-producing organisms in mice was also demonstrated with piperacillin plus inhibitor. Median effective doses were reduced by approximately two- to eightfold compared to those of piperacillin alone when the drug was combined with the various inhibitors at a 4:1 ratio. Pharmacokinetic analysis after intravenous administration of the various inhibitors showed mean residence times of 0.1 to 0.5 h, clearance rates of 15 to 81 ml/min/kg, and volumes of distribution between 0.4 and 2.5 liters/kg. The novel methylidene penem molecules inhibit both class A and class C enzymes and warrant further investigation for potential as therapeutic agents when used in combination with a β-lactam antibiotic.

scholarly journals REFRACTORY FUNGAL VAGINITIS TREATED BY TOPICAL AMPHOTERICIN B. Review

2020 ◽  
Vol 16 (2) ◽  
pp. 55-58
Author(s):  
Falah Hasan Obayes AL-Khikani
Keyword(s):  
Antifungal Activity ◽  
Side Effects ◽  
Amphotericin B ◽  
Intravenous Injection ◽  
Fungal Infections ◽  
Wide Spectrum ◽  
Candida Spp

Vaginitis is a common problem for women regarding a worldwide health challenge with many side effects. Vaginitis is among the most visiting to gynecology clinics. About 75% of all reproductive women had at least one fungal vaginitis infection in their life, and more than 40% will have two or more than two.  Candida spp is the most prevalent in fungal vaginitis, while reports for unusual fungi were observed as mucor spp. Amphotericin B (AmB) belongs to the polyene group has a wide spectrum in vitro and in vivo antifungal activity. All of the known available formulas of AmB are administrated via intravenous injection to treat severe systemic fungal infections, while the development of the topical formula of AmB is still under preliminary development including topical vaginal AmB. Due to the revealing of antimicrobial-resistant fungi in recent years, this study explains the role of topical AmB in treating refractory fungi vaginitis that may not a response to other drugs reported in many cases that may help researchers to develop new effective formula of AmB regarding fungal vaginitis.

scholarly journals T-8581, a new orally and parenterally active triazole antifungal agent: in vitro and in vivo evaluations.

1997 ◽  
Vol 41 (1) ◽  
pp. 30-34 ◽  
Author(s):  
A Yotsuji ◽  
K Shimizu ◽  
H Araki ◽  
K Fujimaki ◽  
N Nishida ◽  
...  
Keyword(s):  
Optical Density ◽  
Antifungal Agent ◽  
Geometric Mean ◽  
Water Soluble ◽  
Concentration Time ◽  
Effective Doses ◽  
High Concentrations ◽  
Drug Free

T-8581 is a new water-soluble triazole antifungal agent. The geometric mean IC80s (GM-IC80S; where the IC80 is the lowest drug concentration which reduced the optical density at 630 nm by 80% compared with the optical density at 630 nm of the drug-free control) for Candida albicans were as follows: T-8581, 0.218 microgram/ml; fluconazole; 0.148 microgram/ml; and itraconazole, 0.0170 microgram/ml. For Cryptococcus neoformans the GM-IC80s were as follows: T-8581, 9.28 micrograms/ml; fluconazole, 4.00 micrograms/ml; and itraconazole, 0.119 microgram/ml. For Aspergillus fumigatus the GM-IC80s were as follows: T-8581, 71.0 micrograms/ml; fluconazole, 239 micrograms/ml; and itraconazole, 0.379 microgram/ml. Against systemic candidiasis in mice, the 50% effective doses (ED50s) of T-8581, fluconazole, and itraconazole (given orally) were 0.412, 0.392, and > 320 mg/kg of body weight, respectively. Against systemic aspergillosis in mice, the ED50s of T-8581, fluconazole, and itraconazole (given orally) were 50.5, 138, > 320 mg/kg, respectively. T-8581 was also efficacious when it was given parenterally (ED50, 59.2 mg/kg), while the ED50 of fluconazole given parenterally was > 20 mg/kg. Against systemic aspergillosis in rabbits, T-8581 was more effective than fluconazole and itraconazole in prolonging the life span. The high concentrations of T-8581 were observed in the sera of mice, rats, rabbits and dogs. Species differences in half-lives and areas under the concentration-time curves were observed, with the values for mice, rats, rabbits, and dogs increasing in that order. These results suggest that T-8581 would be a potentially effective antifungal drug for oral and parenteral use.

scholarly journals Neurokinin-3 Receptor Binding in Guinea Pig, Monkey, and Human Brain: In Vitro and in Vivo Imaging Using the Novel Radioligand, [18F]Lu AF10628

2016 ◽  
Vol 19 (8) ◽  
pp. pyw023
Author(s):  
Katarina Varnäs ◽  
Sjoerd J. Finnema ◽  
Vladimir Stepanov ◽  
Akihiro Takano ◽  
Miklós Tóth ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Human Brain ◽  
Receptor Binding ◽  
In Vivo Imaging ◽  
The Novel ◽  
Neurokinin 3 Receptor

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

1976 ◽  
Vol 36 (02) ◽  
pp. 401-410 ◽  
Author(s):  
Buichi Fujttani ◽  
Toshimichi Tsuboi ◽  
Kazuko Takeno ◽  
Kouichi Yoshida ◽  
Masanao Shimizu
Keyword(s):  
Guinea Pig ◽  
Acetylsalicylic Acid ◽  
Guinea Pigs ◽  
Glass Bead ◽  
Animal Species ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value

2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan
Keyword(s):  
Side Effects ◽  
Medicinal Plants ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Psidium Guajava ◽  
Current Status ◽  
Future Perspective ◽  
Wide Range

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.

Mannose Conjugated Starch Nanoparticles for Preferential Targeting of Liver Cancer

2020 ◽  
Vol 17 ◽  
Author(s):  
Akhlesh Kumar Jain ◽  
Hitesh Sahu ◽  
Keerti Mishra ◽  
Suresh Thareja
Keyword(s):  
Side Effects ◽  
Liver Cancer ◽  
Entrapment Efficiency ◽  
Xrd Analysis ◽  
In Vitro Cytotoxicity ◽  
Physical Interaction ◽  
Scanning Calorimetry ◽  
Starch Nanoparticles

Aim: To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for site specific delivery. Background: Liver cancer is the third leading cause of death in world and fifth most often diagnosed cancer is the major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation challenge, it is necessary to develop novel target specific drug delivery system for the effective and better localization of drug into the proximity of target with restricting the movement of drug in normal tissues. Objective: To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for effective treatment of liver cancer. Materials and methods: 5-FU loaded JFSSNPs were prepared and optimized formulation had higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. Potential of NPs were studied using in vitro cytotoxicity assay, in vivo kinetic studies and bio-distribution studies. Result and discussion: 5-Fluorouracil loaded NPs had particle size between 336 to 802nm with drug entrapment efficiency was between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of drug in amorphous form. DSC study suggests there was no physical interaction between 5- FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assist selective accumulation of 5-FU in the liver (vs other organs spleen, kidney, lungs and heart) compared to unconjugated one and plain drug. Conclusion: In vivo, bio-distribution and plasma profile studies resulted in significantly higher concentration of 5- Fluorouracil liver suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer.

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