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Yakugaku Zasshi : Journal of the... 2024The Japanese package insert (J-PI) for nirmatrelvir/ritonavir (N/r) (specially approved pharmaceutical) includes numerous warnings about drug interactions. However,...
The Japanese package insert (J-PI) for nirmatrelvir/ritonavir (N/r) (specially approved pharmaceutical) includes numerous warnings about drug interactions. However, discrepancies in the information on drug interaction are reported between J-PI and foreign databases. This study aimed to evaluate various information sources on N/r drug interactions. We categorized and compared information on N/r drug interactions from the J-PI, prescribing information from foreign regulatory agencies, guidance from the National Institutes of Health and University Health Network, the Ontario coronavirus disease 2019 (COVID-19) Science Advisory Table, University of Liverpool, Lexicomp, and the Japanese Society of Pharmaceutical Health Care and Sciences (JSPHCS). We assessed information quantity, missing data in J-PI, predicted change of the area under the blood concentration-time curve (AUC) for nirmatrelvir or co-administered drugs, and the information source consistency. From these information sources, we compiled a dataset with 115 contraindications and 203 precautions for N/r co-administration, and 51 contraindications are missing in J-PI. Among them, at least 12 drugs have large predicted AUC changes with N/r (AUC ≥5-fold or <1/5 of the baseline value). Nine of these 12 drugs are included as contraindications in Lexicomp and the JSPHCS. The consistency among the information sources is low. Information in the J-PI alone may be insufficient and Lexicomp or the JSPHCS guidelines should be useful because of their large amounts of information and wide coverage of drugs with large AUC changes. Due to low source consistency, multiple sources are needed for clinical management.
Topics: Ritonavir; Humans; Drug Interactions; Drug Combinations; COVID-19 Drug Treatment; Lopinavir; Area Under Curve; Japan; Indazoles
PubMed: 38945847
DOI: 10.1248/yakushi.23-00204 -
The Journal of Toxicological Sciences 2024Clothianidin (CLO), a neonicotinoid that is widely used in forests and agricultural areas, was recently reported to cause toxicity in mammals. Although sensitivity to...
Clothianidin (CLO), a neonicotinoid that is widely used in forests and agricultural areas, was recently reported to cause toxicity in mammals. Although sensitivity to chemicals varies between sexes and developmental stages, studies that comprehensively evaluate both males and females are limited. Therefore, in this study we utilized murine models to compare the sex-specific differences in behavioral effects following CLO exposure at different developmental stages. We orally administered CLO to male and female mice as a single high-dose solution (80 mg/kg) during the postnatal period (2-week-old), adolescence (6-week-old), or maturity (10-week-old), and subsequently evaluated higher brain function. The behavioral battery test consisted of open field, light/dark transition, and contextual/cued fear conditioning tests conducted at three and seven months of age. After the behavioral test, the brains were dissected and prepared for immunohistochemical staining. We observed behavioral abnormalities in anxiety, spatial memory, and cued memory only in female mice. Moreover, the immunohistochemical analysis showed a reduction in astrocytes within the hippocampus of female mice with behavioral abnormalities. The behavioral abnormalities observed in female CLO-treated mice were consistent with the typical behavioral abnormalities associated with hippocampal astrocyte dysfunction. It is therefore possible that the CLO-induced behavioral abnormalities are at least in part related to a reduction in astrocyte numbers. The results of this study highlight the differences in behavioral effects following CLO exposure between sexes and developmental stages.
Topics: Animals; Female; Neonicotinoids; Guanidines; Male; Behavior, Animal; Thiazoles; Hippocampus; Sex Characteristics; Fear; Astrocytes; Anxiety; Mice; Sex Factors; Spatial Memory; Administration, Oral; Insecticides
PubMed: 38945841
DOI: 10.2131/jts.49.301 -
Brain and Behavior Jul 2024Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic knowledge, working memory, and executive function....
INTRODUCTION
Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic knowledge, working memory, and executive function. Similar to patients with Parkinson's disease (PD), patients with progressive supranuclear palsy (PSP) scored lower than healthy adults in the well-established semantic fluency test. However, it is unclear how unique are the produced words. This study examined the relationship between semantic fluency and words' uniqueness in patients with PSP.
METHODS
Twenty-seven patients with PSP Richardson's syndrome (PSP-RS), 37 patients with PD, and 41 healthy controls (HC) performed a standard semantic fluency test (animals), and their verbal responses were audio-recorded. We used the uniqueness to reflect the ability to produce both original and effective work, that is, creativity.
RESULTS
The PSP-RS group produced fewer correct words and fewer unique words than the PD and HC groups. Moreover, the correlation between fluency and uniqueness was positive in the HC and PD groups but negative in the PSP-RS group. Importantly, the actual levodopa dose was positively correlated with the fluency but negatively correlated with the uniqueness in PSP-RS. The PSP-RS patients who took a greater dose of levodopa tended to produce more correct words but fewer unique words.
CONCLUSIONS
These results suggested that levodopa may modulate semantic fluency and uniqueness in the early stages of PSP-RS.
Topics: Humans; Supranuclear Palsy, Progressive; Male; Female; Aged; Semantics; Levodopa; Parkinson Disease; Middle Aged; Neuropsychological Tests; Antiparkinson Agents
PubMed: 38945805
DOI: 10.1002/brb3.3606 -
The Journal of Sexual Medicine Jun 2024
Topics: Humans; Testosterone; Male; Fertility Preservation; Hormone Replacement Therapy
PubMed: 38945687
DOI: 10.1093/jsxmed/qdae046 -
Journal of Thrombosis and Haemostasis :... Jul 2024
Topics: Humans; Vitamin K; Perioperative Care; Anticoagulants; Blood Coagulation
PubMed: 38945667
DOI: 10.1016/j.jtha.2024.04.012 -
Annales Pharmaceutiques Francaises Jun 2024Nanosuspensions have emerged as a promising avenue in pharmaceutical innovation, particularly for enhancing the bioavailability of poorly soluble medications. This... (Review)
Review
INTRODUCTION
Nanosuspensions have emerged as a promising avenue in pharmaceutical innovation, particularly for enhancing the bioavailability of poorly soluble medications. This article explores the transformative potential of nanosuspensions, emphasizing the critical role of particle size reduction through nanonization techniques. With conventional approaches often falling short in addressing the bioavailability challenges of hydrophobic drugs, nanosuspensions offer multifaceted applications and distinctive advantages in drug delivery.
METHODS
The study delves into various nanosuspension preparation techniques, including high-pressure homogenization, media milling, emulsification-solvent evaporation, precipitation, and supercritical fluid processes. Each method brings unique advantages and limitations, contributing to the expanding repertoire of nanosuspension formulation methods. The article emphasizes the necessity for meticulous planning, evaluation, and ongoing research across different drugs to optimize their use effectively.
RESULTS
Nanosuspensions exhibit versatility in administration routes, spanning parenteral, peroral, ocular, and pulmonary pathways, making them applicable across diverse dosage forms. Current efforts are directed towards furthering their application in site-specific medication administration, indicating their potential in tailored therapeutic strategies. Nanosuspensions offer a promising solution for enhancing drug solubility and bioavailability, addressing the persistent challenge of poor solubility in pharmaceutical compounds.
DISCUSSION
The significance of careful formulation and stabilization using polymers and surfactants is underscored, ensuring the efficacy and safety of nanosuspensions. By discussing the benefits, drawbacks, and nuances of each preparation technique, the article aims to simplify future research endeavors in the field of nanosuspensions. Additionally, a comprehensive overview of nanosuspensions, including their preparation methods, benefits, characterization, patents, marketed products, and intended uses, sheds light on this evolving domain in pharmaceutical sciences.
CONCLUSION
Nanosuspensions represent a promising approach for overcoming bioavailability challenges associated with poorly soluble medications. The article highlights their transformative potential in pharmaceutical innovation, emphasizing the importance of continued research and optimization to harness their benefits effectively. Nanosuspensions offer a viable solution for enhancing drug solubility and bioavailability, with implications for improving therapeutic outcomes in various medical conditions.
PubMed: 38945393
DOI: 10.1016/j.pharma.2024.06.003 -
Annales Pharmaceutiques Francaises Jun 2024The present work represents a reverse-phase high-performance liquid chromatography method in addition to stability studies for sequential estimation of Remogliflozin...
OBJECTIVE
The present work represents a reverse-phase high-performance liquid chromatography method in addition to stability studies for sequential estimation of Remogliflozin Etabonate, Vildagliptin, and Metformin HCl in tablet formulation.
METHOD
The mentioned method utilizes a Phenomenex Luna C18 column (250 × 4.6 mm, 5 μm). It consists of a column oven's temperature of 35 ͦ C. Mobile phase includes a mixture of 50% Phosphate buffer (pH - 6.8) and 50% Acetonitrile along with a flow rate of 0.8 mL/min and 20 minutes of run time. The injection volume was 20 μL. 217 nm is a detection wavelength, and a PDA detector is used for detection.
RESULTS
The suggested technique was proven and validated per the ICH Q2(R1) guideline. The combination was put under stress conditions that included acid, base, thermal, photolytic, and oxidative degradation. The combination was considerably degraded under oxidative, acidic, and basic circumstances for deterioration, and the degradation results were accurately identified from the observed peaks, demonstrating the method's effectiveness in detecting stability.
CONCLUSION
The technique was quick, precise, sensitive, and accurate; as a result, it may be used in quality control laboratories and the pharmaceutical industry for routine quality monitoring of tablets containing all three medications.
PubMed: 38945392
DOI: 10.1016/j.pharma.2024.06.006 -
International Journal of Antimicrobial... Jun 2024Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore...
PURPOSE
Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore potential factors to influence its effectiveness and safety.
METHODS
A Model-Based Meta-Analysis (MBMA) of 96 articles was conducted, focusing on factors like dosage, bacterial species, and combined antibiotic therapy. The analysis evaluated mortality rates and incidence rate of renal dysfunction, also employing parametric survival models to assess 30-day survival rates.
RESULTS
In the study involving 96 articles and 9,716 patients, polymyxin B's daily dose showed minimal effect on overall mortality, with high-dose group mortality at 33.57% (95% CI: 29.15-38.00) compared to the low-dose group at 35.44% (95% CI: 28.99-41.88), p=0.64. Mortality significantly varied by bacterial species, with Pseudomonas aeruginosa infections at 58.50% (95% CI: 55.42-63.58). Monotherapy exhibited the highest mortality at 40.25% (95% CI: 34.75-45.76), p<0.01. Renal dysfunction was more common in high-dose patients at 29.75% (95% CI: 28.52-30.98), with no significant difference across antibiotic regimens, p=0.54. The 30-day Overall Survival rate for monotherapy therapy was 63.6% (95% CI: 59.3-67.5) and 70.2% (95% CI: 64.4-76.2) for association therapy with β-lactam drugs.
CONCLUSIONS
The dosage of Polymyxin B doesn't significantly change death rates, but its effectiveness varies based on the bacterial infection. Certain bacteria like Pseudomonas aeruginosa are associated with higher mortality. Combining Polymyxin B with other antibiotics, especially β-lactam drugs, improves survival rates. Side effects depend on the dose, with lower doses being safer. These findings emphasize the importance of customizing treatment to balance effectiveness and safety.
PubMed: 38945178
DOI: 10.1016/j.ijantimicag.2024.107262 -
Ultrasonics Sonochemistry Jun 2024The study aimed to extract and encapsulate betalain pigment from prickly pear (Opuntia ficus-indica) using ultrasound-assisted extraction and eco-friendly glycerol....
The study aimed to extract and encapsulate betalain pigment from prickly pear (Opuntia ficus-indica) using ultrasound-assisted extraction and eco-friendly glycerol. Subsequent analysis encompassed assessing its thermal stability, shelf-life, bio-accessibility, and biological properties. The process optimization employed Response Surface Methodology (RSM), focusing on glycerol concentration (20-50 %), sample to solvent ratio (1:10-1:20), temperature (30-60 °C), and time (10-30 min). Optimal conditions were determined as 23.15 % glycerol, 1:10 sample to solvent ratio, 10.43 min treatment time, and 31.15 °C temperature. Under these conditions, betalain content reached 858.28 mg/L with a 93.76 % encapsulation efficiency. Thermal stability tests (80-180 °C; 30 & 60 min) showed degradation of betalain with higher temperatures and longer durations, affecting the visual aspect (ΔE) of the pigment. Encapsulated betalain exhibited favorable shelf stability, with optimal storage life of 404.27 days at 4 °C in amber conditions, compared to 271.99 days at 4 °C without amber, 141.92 days at 25 °C without amber, and 134.22 days at 25 °C with amber. Bio-accessibility of encapsulated betalain was significantly higher (2.05 ± 0.03 %) than conventionally extracted pigment (1.03 ± 0.09 %). The encapsulated pigment displayed strong anti-inflammatory properties in dosages of 2-20 µL, with no cytotoxic effects. Additionally, incorporation into gummies was successful and visually approved by sensory panellists. Glycerol proved to be a green encapsulating agent for betalain, offering high shelf life and bio-accessibility, making it suitable for food industry applications. The encapsulated pigment demonstrated robust thermal stability and shelf life, making it suitable for food industry applications. This study highlights glycerol's potential as a sustainable alternative for natural pigment extraction.
PubMed: 38945052
DOI: 10.1016/j.ultsonch.2024.106975 -
Journal of Nutritional Science and... 2024Osteoporosis is characterized by bone loss and deterioration in bone microstructure, leading to bone fragility. It is strongly correlated with menopause in women....
Osteoporosis is characterized by bone loss and deterioration in bone microstructure, leading to bone fragility. It is strongly correlated with menopause in women. Previously, we reported that diets supplemented with a kudzu (Pueraria lobata) vine extract suppressed bone resorption in ovariectomized (OVX) mice, a postmenopausal model. The main isoflavone in kudzu is puerarin (daidzein-8-C-glycoside). Puerarin (daidzein-8-C-glycoside), which is main isoflavone of kudzu, probably contributes to the beneficial effect. However, the underlying mechanism is unclear. Therefore, the nutrikinetics of puerarin and the comparison with the suppressive effects of kudzu isoflavones on osteoclast differentiation was examined in this study. We demonstrated that orally administered puerarin was absorbed from the gut and entered the circulation in an intact form. In addition, puerarin accumulated in RAW264.7 pre-osteoclast cells in a time-dependent manner. Tartrate-resistant acid phosphatase activity was decreased by puerarin treatment in a concentration-dependent manner in RAW264.7 cells stimulated with the receptor activator of nuclear factor kappa-B ligand. Ovariectomy-induced elevated bone resorption was suppressed, and the fragile bone strength was improved by puerarin ingestion in the diet. These findings suggested that orally administered puerarin was localized in bone tissue and suppressed bone resorption and osteoclastogenesis in ovariectomized mice.
Topics: Animals; Isoflavones; Ovariectomy; Osteoclasts; Female; Mice; Femur; Pueraria; Cell Differentiation; RAW 264.7 Cells; Bone Resorption; Plant Extracts; Osteoporosis; Tartrate-Resistant Acid Phosphatase
PubMed: 38945892
DOI: 10.3177/jnsv.70.262