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Drug Metabolizing Enzymes: An Exclusive Guide into Latest Research in Pharmaco-genetic Dynamics in Arab Countries
Authors: Laith AL Eitan, Iliya Yacoub Khair and Saif AlahmadAvailable online: 08 October 2024More LessDrug metabolizing enzymes play a crucial role in the pharmacokinetics and pharmacodynamics of therapeutic drugs, influencing their efficacy and safety. This review explores the impact of genetic polymorphisms in drug-metabolizing genes on drug response within Arab populations. We examine the genetic diversity specific to Arab countries, focusing on the variations in key drug-metabolizing enzymes such as CYP450, GST, and UGT families. The review highlights recent research on polymorphisms in these genes and their implications for drug metabolism, including variations in allele frequencies and their effects on therapeutic outcomes. Additionally, the paper discusses how these genetic variations contribute to the variability in drug response and adverse drug reactions among individuals in Arab populations. By synthesizing current findings, this review aims to provide a comprehensive understanding of the pharmacogenetic landscape in Arab countries and offer insights into personalized medicine approaches tailored to genetic profiles. The findings underscore the importance of incorporating pharmacogenetic data into clinical practice to enhance drug efficacy and minimize adverse effects, ultimately paving the way for more effective and individualized treatment strategies in the region.
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Unveiling the Interplay: Antioxidant Enzyme Polymorphisms and Oxidative Stress in Preterm Neonatal Renal and Hepatic Functions
Authors: Kannan Sridharan and Mona Al JufairiAvailable online: 08 October 2024More LessAimsTo explore the relationship between oxidative stress biomarkers and the occurrence of acute kidney injury (AKI) alongside notable liver function disturbances in preterm neonates.
BackgroundGiven the immaturity of kidneys and incomplete liver development in preterm neonates, oxidative stress poses a considerable threat to their renal and hepatic health.
ObjectiveTo find out the association between various oxidative stress biomarkers and polymorphisms of antioxidant enzymes with renal and live functions.
MethodsIn this cross-sectional study, we gathered umbilical cord blood and peripheral blood samples for assessing oxidative stress biomarkers and identifying single nucleotide polymorphisms (SNPs) in antioxidant enzymes. Utilizing enzyme-linked immunosorbent assay kits, we quantified these oxidative stress biomarkers. Receiver-operating characteristics curve analysis was employed to ascertain the predictive capacity of these biomarkers, denoted by the area-under-the-curve (AUC).
ResultsOur findings revealed that umbilical cord heat-shock proteins emerged as robust predictors of neonatal AKI (AUC: 0.92; 95% CI: 0.8-1) with a defined cut-off concentration of 1.8 ng/mL. Likewise, umbilical cord 8-hydroxy-2-deoxy guanosine demonstrated significant predictability for liver function alterations (AUC: 0.7; 95% CI: 0.6-0.9) at a cut-off concentration of 2487.6 pg/mL.
ConclusionsWe observed significant associations between SNPs in endothelial nitric oxide synthase and catalase with both AKI and impaired liver functions. Prospective studies are warranted to validate these findings, with a particular focus on exploring potential antioxidant interventions aimed at mitigating AKI and liver function abnormalities.
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Quality by Design Approach for the Development of Cariprazine Hydrochloride Loaded Lipid-Based Formulation for Brain Delivery via Intranasal Route
Authors: Pallavi Chiprikar, Vinayak Mastiholimath, Prakash Biradar and Nisha ShirkoliAvailable online: 03 October 2024More LessBackgroundCariprazine (CPZ) is a third-generation antipsychotic medication that has been approved for treating schizophrenia. This study aimed to develop a cariprazine-loaded nanostructured lipid carrier (CPZ-NLCs) to prevent first-pass metabolism and improve bioavailability and site-specific delivery from nose to the brain.
MethodThe CPZ-NLCs were prepared using melt emulsification. The formulation was optimized using the Box–Behnken design (BBD); where the influence of independent variables on critical quality attributes, such as particle size and entrapment efficiency was studied.
ResultThe optimized batch (F6) had a particle size of 173.3 ± 0.6 nm and an entrapment efficiency of 96.1 ± 0.57%, respectively. The in vitro release showed >96% release of CPZ from NLC within 30 min. The optimized formulation's ex vivo studies revealed significantly increased CPZ permeability (>75%) in sheep nasal mucosa compared to the CPZ suspension (~26%). The ciliotoxicity study of the nasal mucosa revealed that the CPZ-NLC formulation did not affect the nasal epithelium. The intranasal administration of the formulation achieved 76.14±6.23 µg/ml concentration in the brain which was significantly higher than the oral CPZ suspension administration (30.46±7.24 µg/ml). The developed formulation was stable for 3 months.
ConclusionThe study concluded that the developed CPZ-NLC could significantly improve the bioavailability with quick delivery to the brain.
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