Challenges in confirming drug effectiveness after early approval

Science ◽  
2021 ◽  
Vol 374 (6572) ◽  
pp. 1205-1207
Author(s):  
Holly Fernandez Lynch ◽  
Christopher T. Robertson
Keyword(s):  
Drug Effectiveness

Gestagens in assisted reproductive technology programs

GYNECOLOGY ◽  
2019 ◽  
Vol 21 (2) ◽  
pp. 76-79
Author(s):  
Anastasia G Syrkasheva ◽  
Yana A Petrosyan ◽  
Natalia V Dolgushina
Keyword(s):  
Assisted Reproductive Technology ◽  
Luteal Phase ◽  
Ovarian Hyperstimulation Syndrome ◽  
Infertility Treatment ◽  
Reproductive Technology ◽  
Art Programs ◽  
Drug Effectiveness ◽  
Essential Step ◽  
Endogenous Steroid ◽  
Endogenous Steroid Hormones

Background. Luteal phase (LP) drug support is an important step in assisted reproductive technology (ART) programs efficacy. Aim. To present up-to-date data on an efficacy of LP hormonal support during ART cycles as well as to conduct a comparative analysis of various gestagen drug effectiveness. Materials and methods. To write this review domestic and foreign publications were searched in Russian and international search systems (PubMed, eLibrary, etc.) for the last 8 years. The review includs articles from peer-reviewed literature. Results. LP drug support becomes an essential step in infertility treatment in various ART programs. Although human chorionic gonadotropin drug injections in the posttransfer period leads to an activation of endogenous steroid hormones synthesis, exogenous hormones use is currently preferred because of not having a risk of ovarian hyperstimulation syndrome. Conclusions. The variety of progesterone drugs is accompanied by a lack of algorithms for their use in various clinical situations. Further studies are required to evaluate progesterone drugs efficacy for various subgroups of patients.

Improved drug delivery system for cancer treatment by D-glucose conjugation with eugenol from natural product

2020 ◽  
Vol 17 ◽  
Author(s):  
Mas Amira Idayu Abdul Razak ◽  
Haslinda Abdul Hamid ◽  
Raja Nor Izawati Raja Othman ◽  
Shaik Alaudeen Mohd Moktar ◽  
Azizi Miskon
Keyword(s):  
Drug Delivery ◽  
Water Solubility ◽  
Osteosarcoma Cell ◽  
Drug Effectiveness ◽  
H Nmr ◽  
Proliferative Effect ◽  
Conventional Drug ◽  
Ic50 Value ◽  
Glucose Conjugation ◽  
Diphenyl Tetrazolium Bromide

Introduction: Bioconjugations are swiftly progressing and are being applied to solve several limitations of conventional drug delivery systems (DDS) such as lack of water solubility, non-specific, and poor bioavailability. The main goals of DDS are to achieve greater drug effectiveness and minimize toxicity to the healthy tissues. Objectives: In this study, D-glucose was conjugated with eugenol to target the cancer cells. To identify the implication of the anticancer effect, osteosarcoma (K7M2) cells were cultured and the anti-proliferative effect was performed using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay] test in order to evaluate the viability and toxicity on cells with various concentrations of eugenol and D-glucose-eugenol conjugate in 24-hour incubation. Results: It was found that, the successful confirmation of the conjugation between D-glucose and eugenol was obtained by 1 H NMR spectroscopy. MTT assay showed inhibitory concentration (IC50 value) of D-glucose-eugenol was at 96.2 µg/ml and the decreased of osteosarcoma cell survival was 48%. Conclusion: These findings strongly indicate that K7M2 cells would be affected by toxicity of D-glucose-eugenol. Therefore, the present study suggests that D-glucose-eugenol has high potential to act as an anti-proliferative agent who may promise a new modality or approach as the drug delivery treatment for cancer or chemotherapeutic agent.

scholarly journals Clock/Sleep-Dependent Learning and Memory in Male 3xTg-AD Mice at Advanced Disease Stages and Extrinsic Effects of Huprine X and the Novel Multitarget Agent AVCRI104P3

2021 ◽  
Vol 11 (4) ◽  
pp. 426
Author(s):  
Lydia Giménez-Llort ◽  
Mikel Santana-Santana ◽  
Míriam Ratia ◽  
Belén Pérez ◽  
Pelayo Camps ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Advanced Disease ◽  
Active Phase ◽  
Task Demands ◽  
The Novel ◽  
Training Time ◽  
Drug Effectiveness ◽  
Dependent Learning ◽  
Disease Stages

A new hypothesis highlights sleep-dependent learning/memory consolidation and regards the sleep-wake cycle as a modulator of β-amyloid and tau Alzheimer’s disease (AD) pathologies. Sundowning behavior is a common neuropsychiatric symptom (NPS) associated with dementia. Sleep fragmentation resulting from disturbances in sleep and circadian rhythms in AD may have important consequences on memory processes and exacerbate the other AD-NPS. The present work studied the effect of training time schedules on 12-month-old male 3xTg-AD mice modeling advanced disease stages. Their performance in two paradigms of the Morris water maze for spatial-reference and visual-perceptual learning and memory were found impaired at midday, after 4 h of non-active phase. In contrast, early-morning trained littermates, slowing down from their active phase, exhibited better performance and used goal-directed strategies and non-search navigation described for normal aging. The novel multitarget anticholinesterasic compound AVCRI104P3 (0.6 µmol·kg−1, 21 days i.p.) exerted stronger cognitive benefits than its in vitro equipotent dose of AChEI huprine X (0.12 μmol·kg−1, 21 days i.p.). Both compounds showed streamlined drug effectiveness, independently of the schedule. Their effects on anxiety-like behaviors were moderate. The results open a question of how time schedules modulate the capacity to respond to task demands and to assess/elucidate new drug effectiveness.

Plasmonic Nanosensors for the Determination of Drug Effectiveness on Membrane Receptors

2016 ◽  
Vol 9 (1) ◽  
pp. 218-223 ◽  
Author(s):  
Rubén Ahijado-Guzmán ◽  
Julia Menten ◽  
Janak Prasad ◽  
Christina Lambertz ◽  
Germán Rivas ◽  
...  
Keyword(s):  
Membrane Receptors ◽  
Drug Effectiveness

Indicators of Drug Effectiveness

Science ◽  
1971 ◽  
Vol 173 (4000) ◽  
pp. 870-870
Author(s):  
K. Johnson
Keyword(s):  
Drug Effectiveness

scholarly journals Pharmacokinetic-pharmacodynamic correlation of imipenem in pediatric burn patients using a bioanalytical liquid chromatographic method

2015 ◽  
Vol 51 (2) ◽  
pp. 305-315 ◽  
Author(s):  
Silvia Regina Cavani Jorge Santos ◽  
Cristina Sanches-Giraud ◽  
Carlindo Vieira Silva Júnior ◽  
David Souza Gomez
Keyword(s):  
Burn Patients ◽  
Sample Collection ◽  
Bioanalytical Method ◽  
Drug Effectiveness ◽  
Drug Concentrations ◽  
Liquid Chromatographic Method ◽  
Binary Mobile Phase ◽  
Critical Patients ◽  
Liquid Chromatographic ◽  
Plasma Measurements

<p>A bioanalytical method was developed and applied to quantify the free imipenem concentrations for pharmacokinetics and PK/PD correlation studies of the dose adjustments required to maintain antimicrobial effectiveness in pediatric burn patients. A reverse-phase Supelcosil LC18 column (250 x 4.6 mm 5 micra), binary mobile phase consisting of 0.01 M, pH 7.0 phosphate buffer and acetonitrile (99:1, v/v), flow rate of 0.8 mL/min, was applied. The method showed good absolute recovery (above 90%), good linearity (0.25-100.0 µg/mL, r<sup>2</sup>=0.999), good sensitivity (LLOQ: 0.25 µg/mL; LLOD: 0.12 µg/mL) and acceptable stability. Inter/intraday precision values were 7.3/5.9%, and mean accuracy was 92.9%. A bioanalytical method was applied to quantify free drug concentrations in children with burns. Six pediatric burn patients (median 7.0 years old, 27.5 kg), normal renal function, and 33% total burn surface area were prospectively investigated; inhalation injuries were present in 4/6 (67%) of the patients. Plasma monitoring and PK assessments were performed using a serial blood sample collection for each set, totaling 10 sets. The PK/PD target attained (40%T>MIC) for each minimum inhibitory concentration (MIC: 0.5, 1.0, 2.0, 4.0 mg/L) occurred at a percentage higher than 80% of the sets investigated and 100% after dose adjustment. In conclusion, the purification of plasma samples using an ultrafiltration technique followed by quantification of imipenem plasma measurements using the LC method is quite simple, useful, and requires small volumes for blood sampling. In addition, a small amount of plasma (0.25 mL) is needed to guarantee drug effectiveness in pediatric burn patients. There is also a low risk of neurotoxicity, which is important because pharmacokinetics are unpredictable in these critical patients with severe hospital infection. Finally, the PK/PD target was attained for imipenem in the control of sepsis in pediatric patients with burns.</p>

scholarly journals Mutational Analysis of Quinolone-Resistant Determining Region gyrA and parC Genes in Quinolone-Resistant ESBL-Producing E. Coli

2021 ◽  
Vol 20 (3) ◽  
Author(s):  
Hairul Aini Hamzah ◽  
Rahmatullah Sirat ◽  
Mohammed Imad A. Mustafa Mahmud ◽  
Roesnita Baharudin
Keyword(s):  
Mutational Analysis ◽  
Single Point ◽  
Point Mutations ◽  
Multidrug Resistant ◽  
Quinolone Resistance ◽  
Resistant Bacteria ◽  
Single Point Mutation ◽  
Phenotypic Resistance ◽  
Drug Effectiveness ◽  
E Coli

 Introduction: Co-resistance to quinolones among extended spectrum β[1]lactamase (ESBL)-producing E. coli commonly occurs in clinical settings. Quinolones act on DNA gyrase and DNA topoisomerase enzymes, which are coded by gyrA and parC genes, thus any mutation to the genes may affect the drug effectiveness. The objective of the study was to characterize gyrA and parC genes in quinolone-resistant E. coli isolates and correlated the mutations with their phenotypic resistance. Materials and Methods: Thirty-two quinolone-resistant (QR) and six quinolone-sensitive (QS) ESBL-E. coli isolates were identified by antibiotic susceptibility and minimum inhibitory concentration tests. Bioinformatics analysis were conducted to study any mutations occurred in the genes and generate their codon compositions. Results: All the QR ESBL-E. coli isolates were identified as multidrug-resistant bacteria. A single point mutation in the quinolone resistance-determining region (QRDR) of gyrA, at codon 83, caused the substitution amino acid Ser83Leu. It is associated with a high level of resistance to nalidixic acid. However, double mutations Ser83Leu and Asp87Asn in the same region were significantly linked to higher levels of resistance to ciprofloxacin. Cumulative point mutations in gyrA and/or in parC were also correlated significantly (p<0.05) to increased resistance to ciprofloxacin. Conclusion: Together, the findings showed that the mutations in gyrA and parC genes handled the institution of intrinsic quinolone resistance in the ESBL-E. coli isolates. Thus, vigilant monitoring for emergence of new mutation in resistance genes may give an insight into dissemination of QR ESBL-E. coli in a particular region.

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