scholarly journals Comparative Pharmacokinetic Profiles of Puerarin in Rat Plasma by UHPLC-MS/MS after Oral Administration of Pueraria lobata Extract and Pure Puerarin

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Guozhe Zhang ◽  
Jianwei Ji ◽  
Mingzhong Sun ◽  
Yuqiao Ji ◽  
Hongjian Ji
Keyword(s):  
Oral Bioavailability ◽  
Water Solubility ◽  
Biological Activities ◽  
Rat Plasma ◽  
Biologically Active ◽  
Maximum Plasma ◽  
Pueraria Lobata ◽  
Time Curve ◽  
Elimination Half ◽  
Wide Range

Puerarin is the main biologically active isoflavone in Pueraria lobata and has a wide range of biological activities. However, due to its poor water solubility and low oral bioavailability, its clinical applications are restricted. Compared with puerarin, the Pueraria lobata extract (PLE) has better water solubility, lower toxicity, and less side effects. In this study, the pharmacokinetics of orally administered puerarin (100 mg/kg) and PLE (763 mg/kg, equivalent to 100.0 mg/kg of puerarin) to rats was investigated by the UHPLC-MS/MS method. Results showed that when the rats were administered PLE, the area under the concentration-time curve from zero to infinity (AUC0-inf) dramatically increased from 219.83 ± 64.37 μg h/L to 462.62 ± 51.74 μg h/L (p<0.01). The elimination half-time (t1/2) also increased from 1.60 ± 0.38 h to 12.04 ± 5.10 h (p<0.01). The maximum concentration (Cmax) of puerarin decreased from 101.64 ± 41.82 ng/mL to 48.64 ± 21.47 ng/mL (p<0.01), and time to reach the maximum plasma concentration (Tmax) of puerarin decreased from 1.46 ± 1.08 h to 0.54 ± 0.30 h (p<0.01). Results indicated that the pharmacokinetics of puerarin in Pueraria lobata may be dramatically different from pure puerarin in the plasma of rat, and oral bioavailability of puerarin may be increased when PLE was administrated to rats.

scholarly journals Toxicokinetic of phenothrin in rabbits

2021 ◽  
Vol 91 (5) ◽  
pp. 547-558
Author(s):  
Tarık Kaya ◽  
◽  
Gökhan Eraslan
Keyword(s):  
Residence Time ◽  
Mean Residence Time ◽  
Oral Bioavailability ◽  
Area Under The Curve ◽  
Maximum Plasma ◽  
Time Curve ◽  
Elimination Half ◽  
Group 2 ◽  
Compartment Open Model ◽  
Group 1

The toxicokinetics of single dose phenothrin were examined in rabbits. For this aim, a total of 14 New Zealand breed, 2 to 2.5 kg body weight, 6 month-old female rabbits were used. The animals were divided into two groups and each group had 7 animals. Phenothrin was administered intravenously to each animal in group 1, at a dose of 10 mg/kg b.w. and orally to each of the animals in group 2 at the same dose. Dimethyl sulfoxide was used as a solvent in application of phenothrin. Plasma phenothrin levels were measured by gas chromatography equipped with an ECD detector. Toxicokinetic evaluations were made according to the plasma phenothrin level-time curve. Phenothrin was found to be distributed according to the two-compartment open model. The values ​​of elimination half-life (t1/2β), mean residence time (MRT) and area under the curve (AUC0→∞) after intravenous phenothrin administration were 2.57 ± 0.10 h, 2.79 ± 0.09 h and 6893.05 ± 261.26 ng/h/mL, respectively. On the other hand, the maximum plasma concentration (Cmax), time to reach Cmax (tmax), t1/2β, MRT and AUC0→∞ after oral administration were 185.71 ± 8.21 ng/mL, 1.21 ± 0.20 h, 4.24 ± 0.39 h, 6.65 ± 0.54 h and 1054.04 ± 65.90 ng/h/mL, respectively. The oral bioavailability of phenothrin was calculated as 15.29%. Mean residence time was short and oral bioavailability was low. This may be one of the reasons why phenothrin is included in safe pesticides.

scholarly journals Thiazole Ring—A Biologically Active Scaffold

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3166
Author(s):  
Anthi Petrou ◽  
Maria Fesatidou ◽  
Athina Geronikaki
Keyword(s):  
Recent Literature ◽  
Biological Activities ◽  
Literature Survey ◽  
Biologically Active ◽  
Thiazole Ring ◽  
Peer Reviews ◽  
Experimental Drugs ◽  
Wide Range ◽  
Approved Drugs ◽  
Fda Approved Drugs

Background: Thiazole is a good pharmacophore nucleus due to its various pharmaceutical applications. Its derivatives have a wide range of biological activities such as antioxidant, analgesic, and antimicrobial including antibacterial, antifungal, antimalarial, anticancer, antiallergic, antihypertensive, anti-inflammatory, and antipsychotic. Indeed, the thiazole scaffold is contained in more than 18 FDA-approved drugs as well as in numerous experimental drugs. Objective: To summarize recent literature on the biological activities of thiazole ring-containing compounds Methods: A literature survey regarding the topics from the year 2015 up to now was carried out. Older publications were not included, since they were previously analyzed in available peer reviews. Results: Nearly 124 research articles were found, critically analyzed, and arranged regarding the synthesis and biological activities of thiazoles derivatives in the last 5 years.

scholarly journals A REVIEW ON THE SYNTHETIC METHODOLOGIES OF CHROMONES

2018 ◽  
Vol 11 (12) ◽  
pp. 9 ◽  
Author(s):  
Mahathy Vanguru ◽  
Ramchander Merugu ◽  
Swetha Garimella ◽  
Laxminarayana E
Keyword(s):  
Biological Activities ◽  
Biologically Active ◽  
Biological Applications ◽  
Essential Component ◽  
Wide Range ◽  
Synthetic Methodologies ◽  
New Compounds

Chromones group of compounds and their derivatives form the essential component of pharmacophores in many biologically active molecules. They exhibit a wide range of biological activities such as antibiotic, antitumor, antiviral, antioxidant, antipsychotic, and antihypoxic activities. These applications have stimulated a continuous search for the synthesis of new compounds in this field and are being extensively investigated. The various methodologies so far reported for the synthesis of these compounds with the compounds biological applications are discussed in this communication

scholarly journals Oral Bioavailability Enhancement and Anti-Fatigue Assessment of the Andrographolide Loaded Solid Dispersion

2020 ◽  
Vol 21 (7) ◽  
pp. 2506 ◽  
Author(s):  
Ching-Chi Yen ◽  
Yu-Kai Liang ◽  
Chao-Pei Cheng ◽  
Mei-Chich Hsu ◽  
Yu-Tse Wu
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersion ◽  
Oral Bioavailability ◽  
Water Solubility ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Amorphous State ◽  
Vehicle Group ◽  
Time To Exhaustion ◽  
Pharmacokinetic Studies

Andrographolide (AG), a major diterpene lactone isolated from Andrographis paniculata (Burm. f.) Nees (Acanthaceae), possesses a wide spectrum of biological activities. However, its poor water solubility and low bioavailability limit its clinical application. Therefore, this study aimed to develop a solid dispersion (SD) formulation to increase the aqueous solubility and dissolution rate of AG. Different drug-polymer ratios were used to prepare various SDs. The optimized formulation was characterized for differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder X-ray diffraction. The analysis indicated that the optimized SD enhanced AG solubility and dissolution rates by changing AG crystallinity to an amorphous state. The dissolution behaviors of the optimum SD composed of an AG-polyvinylpyrrolidone K30-Kolliphor EL ratio of 1:7:1 (w/w/w) resulted in the highest accumulated dissolution (approximately 80%). Pharmacokinetic studies revealed that Cmax/dose and the AUC/dose increased by 3.7-fold and 3.0-fold, respectively, compared with AG suspension. Furthermore, pretreatment using the optimized AG-SD significantly increased the swimming time to exhaustion by 1.7-fold and decreased the plasma ammonia level by 71.5%, compared with the vehicle group. In conclusion, the optimized AG-SD formulation appeared to effectively improve its dissolution rate and oral bioavailability. Moreover, the optimized AG-SD provides a promising treatment against physical fatigue.

Phase I/IIa, randomized, open-label, drug-drug interaction study of trabectedin and rifampin in patients with advanced cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13512-e13512 ◽  
Author(s):  
Arthur P. Staddon ◽  
Trilok V. Parekh ◽  
Roland Elmar Knoblauch ◽  
Chi Keung ◽  
Apexa Bernard ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Locally Advanced ◽  
Plasma Concentrations ◽  
Systemic Exposure ◽  
Maximum Plasma ◽  
Metabolic Clearance ◽  
Open Label ◽  
Time Curve ◽  
Elimination Half ◽  
Cyp3a4 Inducer

e13512 Background: Trabectedin (Yondelis; T) is a tetrahydroisoquinoline compound initially isolated from the marine tunicate, Ecteinascidia turbinata, and currently produced synthetically. It is primarily metabolized by the cytochrome P450 (CYP)3A4 enzyme. Thus, potent inducers or inhibitors of this enzyme may alter the plasma concentrations of T. This study assessed the effects of rifampin (R), a strong CYP3A4 inducer, on the pharmacokinetics (PK) and safety of T. Methods: In this 2-way crossover study, patients (≥18 years of age) with locally advanced or metastatic disease were randomized (1:1) to receive one of the 2 treatment sequences: sequence 1: R plus T followed 28 days later by T; sequence 2: T followed 28 days later by R plus T. During each sequence, R (600 mg/day) was administered for 6 consecutive days and T (1.3 mg/m2, IV) was administered over a 3 hour infusion. Dexamethasone (20 mg, IV) was administered before T administration. PK and safety of T were evaluated with and without coadministration of R. Results: Of the 11 enrolled patients, 8 were PK evaluable. Coadministration of R with T decreased mean maximum plasma concentration (Cmax) by approximately 22% and mean area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast) by approximately 31% (Table 1). Coadministration of R with T also resulted in 23% shorter elimination half-life. Overall, the safety profile of T was comparable when administered alone or with R. Conclusions: In comparison with T alone, coadministration of R resulted in reduced systemic exposure of T in these 8 patients, as measured by Cmax and AUClast. The coadministration of potent inducers of CYP3A4 with T may increase the metabolic clearance of T. Clinical trial information: NCT01273480. [Table: see text]

scholarly journals Comparison of Plasma and Intrapulmonary Concentrations of Nafithromycin (WCK 4873) in Healthy Adult Subjects

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Keith A. Rodvold ◽  
Mark H. Gotfried ◽  
Rakesh Chugh ◽  
Mugdha Gupta ◽  
H. David Friedland ◽  
...  
Keyword(s):  
Healthy Adult ◽  
Plasma Concentrations ◽  
Maximum Plasma ◽  
Total Plasma ◽  
Time Curve ◽  
The Third ◽  
Elimination Half ◽  
The Mean ◽  
Repeated Dosing ◽  
Tract Infections

ABSTRACT The nafithromycin concentrations in the plasma, epithelial lining fluid (ELF), and alveolar macrophages (AM) of 37 healthy adult subjects were measured following repeated dosing of oral nafithromycin at 800 mg once daily for 3 days. The values of noncompartmental pharmacokinetic (PK) parameters were determined from serial plasma samples collected over a 24-h interval following the first and third oral doses. Each subject underwent one standardized bronchoscopy with bronchoalveolar lavage (BAL) at 3, 6, 9, 12, 24, or 48 h after the third dose of nafithromycin. The mean ± standard deviation values of the plasma PK parameters after the first and third doses included maximum plasma concentrations (C max) of 1.02 ± 0.31 μg/ml and 1.39 ± 0.36 μg/ml, respectively; times to C max of 3.97 ± 1.30 h and 3.69 ± 1.28 h, respectively; clearances of 67.3 ± 21.3 liters/h and 52.4 ± 18.5 liters/h, respectively, and elimination half-lives of 7.7 ± 1.1 h and 9.1 ± 1.7 h, respectively. The values of the area under the plasma concentration-time curve (AUC) from time zero to 24 h postdosing (AUC0–24) for nafithromycin based on the mean or median total plasma concentrations at BAL fluid sampling times were 16.2 μg · h/ml. For ELF, the respective AUC0–24 values based on the mean and median concentrations were 224.1 and 176.3 μg · h/ml, whereas for AM, the respective AUC0–24 values were 8,538 and 5,894 μg · h/ml. Penetration ratios based on ELF and total plasma AUC0–24 values based on the mean and median concentrations were 13.8 and 10.9, respectively, whereas the ratios of the AM to total plasma concentrations based on the mean and median concentrations were 527 and 364, respectively. The sustained ELF and AM concentrations for 48 h after the third dose suggest that nafithromycin has the potential to be a useful agent for the treatment of lower respiratory tract infections. (This study has been registered at ClinicalTrials.gov under registration no. NCT02453529.)

scholarly journals Pharmacokinetic Study of an Oral Cephalosporin, Cefdinir, in Hemodialysis Patients

1998 ◽  
Vol 42 (7) ◽  
pp. 1718-1721 ◽  
Author(s):  
Akira Hishida ◽  
Kazuhisa Ohishi ◽  
Satoru Nagashima ◽  
Mitsutaka Kanamaru ◽  
Masao Obara ◽  
...  
Keyword(s):  
Multiple Dose ◽  
Hemodialysis Patients ◽  
Pharmacokinetic Data ◽  
Maximum Plasma ◽  
Oral Cephalosporin ◽  
Time Curve ◽  
Elimination Phase ◽  
Concentration Time ◽  
Elimination Half ◽  
Sufficient Concentration

ABSTRACT The pharmacokinetics of cefdinir were investigated in six hemodialysis patients. For the present study, two tests were carried out, one with 4 h of hemodialysis and the other without hemodialysis. Cefdinir was given orally to each patient in a dose of 100 mg, and blood was collected serially for 48 h after dosing in the test without dialysis and for 72 h in the test with dialysis. In the test without dialysis, the maximum plasma concentration (C max) was 2.36 ± 0.53 μg/ml (mean ± standard deviation) and the time to C max was 9.00 ± 2.45 h. The terminal elimination half-life (t 1/2) and area under the concentration-time curve (AUC) were 16.95 ± 1.20 h and 69.05 ± 14.84 μg · h/ml, respectively. In the test with dialysis,t 1/2 during hemodialysis decreased approximately to one-sixth of that obtained in the test without dialysis, although t 1/2 in the latter elimination phase did not differ from that in the nondialysis test. AUC was reduced to 43% of that in the test without dialysis. The fractional removal of cefdinir by hemodialysis was 61%. These findings indicate that clearance of cefdinir is prolonged in patients with renal failure, and cefdinir is well removed by introduction of hemodialysis, although t 1/2 (during hemodialysis) and AUC were two and eight times higher than the data previously reported for healthy volunteers, respectively. The pharmacokinetic data suggest that 100 mg of oral cefdinir once a day would result in a sufficient concentration in plasma in hemodialysis patients, but this remains to be confirmed by multiple-dose studies.

Green Chemistry Approaches to the Synthesis of Coumarin Derivatives

2020 ◽  
Vol 24 (1) ◽  
pp. 4-43 ◽  
Author(s):  
Maja Molnar ◽  
Melita Lončarić ◽  
Marija Kovač
Keyword(s):  
Energy Consumption ◽  
Green Chemistry ◽  
Biological Activities ◽  
Daily Basis ◽  
Biologically Active ◽  
Synthetic Methods ◽  
Specific Class ◽  
Coumarin Derivatives ◽  
Wide Range ◽  
Coumarin Synthesis

This review is a compilation of the green synthetic methods used in the synthesis of coumarin derivatives. Coumarins are a class of compounds with a pronounced wide range of biological activities, which have found their application in medicine, pharmacology, cosmetics and food industry. Their biological activity and potential application are highly dependent on their structure. Therefore, many researchers have been performing the synthesis of coumarin derivatives on a daily basis. High demands for their synthesis often result in an increased generation of different waste chemicals. In order to minimize the utilization and generation of toxic organic substances, green synthetic methods are applied in this manner. These methods are getting more attention in the last few decades. Green chemistry methods cover a wide range of methods, including the application of ultrasound and microwaves, ionic liquids and deep eutectic solvents, solvent-free synthesis, mechanosynthesis and multicomponent reactions. All typical condensation reactions for coumarin synthesis like Knoevenagel, Perkin, Kostanecki-Robinson, Pechmann and Reformansky reactions, have been successfully performed using these green synthetic methods. According to the authors mentioned in this review, not only these methods reduce the utilization and generation of toxic chemicals, but they can also enhance the reaction performance in terms of product yields, purity, energy consumption and post-synthetic procedures when compared to the conventional methods. Due to the significance of coumarins as biologically active systems and the recent demands of reducing toxic solvents, catalysts and energy consumption, this review provides a first full literature overview on the application of green synthetic methods in the coumarin synthesis. It covers a literature search over the period from 1995-2019. The importance of this work is its comprehensive literature survey on a specific class of heterocyclic compounds, and those researchers working on the coumarin synthesis can find very useful information on the green synthetic approaches to their synthesis. There are some reviews on the coumarin synthesis, but most of them cover only specific reactions on coumarin synthesis and none of them the whole range of green chemistry methods.

3,4-Dihydroisocoumarins, Interesting Natural Products: Isolation, Organic Syntheses and Biological Activities

2019 ◽  
Vol 16 (1) ◽  
pp. 112-129 ◽  
Author(s):  
Aurelio Ortiz ◽  
Miriam Castro ◽  
Estibaliz Sansinenea
Keyword(s):  
Natural Products ◽  
Biological Activities ◽  
Natural Compounds ◽  
Biologically Active ◽  
Bacterial Strains ◽  
Drug Candidates ◽  
Heterocyclic Molecules ◽  
Naturally Occurring ◽  
Wide Range ◽  
Different Sources

Background:3,4-dihydroisocoumarins are an important small group belonging to the class of naturally occurring lactones isolated from different bacterial strains, molds, lichens, and plants. The structures of these natural compounds show various types of substitution in their basic skeleton and this variability influences deeply their biological activities. These lactones are structural subunits of several natural products and serve as useful intermediates in the synthesis of different heterocyclic molecules, which exhibit a wide range of biological activities, such as anti-inflammatory, antiplasmodial, antifungal, antimicrobial, antiangiogenic and antitumoral activities, among others. Their syntheses have attracted attention of many researchers reporting many synthetic strategies to achieve 3,4-dihydroisocoumarins and other related structures. </P><P> Objective: In this context, the isolation of these natural compounds from different sources, their syntheses and biological activities are reviewed, adding the most recent advances and related developments.Conclusion:This review aims to encourage further work on the isolation and synthesis of this class of natural products. It would be beneficial for synthetic as well as the medicinal chemists to design selective, optimized dihydroisocoumarin derivatives as potential drug candidates, since dihydroisocoumarin scaffolds have significant utility in the development of therapeutically relevant and biologically active compounds.

scholarly journals Anti-oxidant and in-vitro alpha amylase inhibitory activities of leaves and barks of Randia dumetorum

2020 ◽  
Author(s):  
Deepak Timalsina
Keyword(s):  
Biological Activities ◽  
Food Poisoning ◽  
Biologically Active ◽  
Alpha Amylase ◽  
Methanolic Extracts ◽  
Therapeutic Uses ◽  
Wide Range ◽  
Pharmaceutical Industries ◽  
The Rich

AbstractThe process of drug discovery and development in the world over a recent year has been increasingly shaped by the formulaic approaches and natural products, prioritized by popular pharmaceutical industries. In many countries like Nepal, Randia dumetorum (Maidal) is one of the popular alternatives for overcoming various symptoms such as acidity, food poisoning ulcers, diabetes and ulcers. It has been using by the people because of its wide range of therapeutic uses. Though, the considerable research had been conducted to reveal the biologically active compounds and its pharmacological effect, the rich constituent of this plant and its major biological perspective was yet to be studied comprehensively. Accordingly, the main focus of this study was the alpha amylase inhibition of methanolic extracts obtained from leaves and barks of Randia dumetorum plant. The plant extracts were obtained by dissolving dried plant with 100% methanol overnight and evaporating to the dryness. The obtained plant extract was used to study mentioned biological activities. The results obtained showed that the extract obtained from leaves and barks showed antioxidant and alpha amylase inhibition activities. This research can be helpful to discover new types of therapeutics in the future.

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