Drug metabolism and personalized therapy最新文献

Objectives: There is an inter-individual in the valsartan response among hypertensive patients. However, clinical factors associated with this variation in the response is still not fully understood. The major purpose of this study is to predict the factors associated with valsartan response and their influence on decreasing blood pressure among patients.

Methods: This study is a cross-sectional observational study. It included 91 hypertensive patients on valsartan treatment, selected through simple random sampling from the Jordan University Hospital. The clinical data was collected through documented medical records in the hospital's computerized system. The data was analyzed using the chi-square test to compare frequencies and categories.

Results: Patients were divided into systolic and diastolic responders. No statistical significance was found between systolic response to valsartan's and gender, smoking, age, BMI, lipid profile and HbA_1c status. Diastolic responders had a positive significance of p value = 0.006 with BMI categories, however there was no significance with any other factor.

Conclusions: There was a better diastolic response to valsartan among hypertensive patients with lower BMI levels. BMI can be considered as a factor to personalize the therapy among patients on valsartan. However, further clinical studies with larger sample size are needed to confirm these data.

Objectives: This study intended to investigate the potential of glucosamine sulfate (GS) as an inhibitor of genes involved in osteoarthritis (OA) development. Despite GS is often used for OA treatment due to its cartilage preservation and minimum side effects, the molecular mechanism behind its interactions remains unknown.

Methods: Molecular docking was conducted to analyze the interactions between glucosamine sulfate and genes associated with OA such as matrix metalloproteinase-3 (MMP-3), MMP-9, and interleukin-4 (IL-4). Additionally, a cell viability assay using RAW 264.7 cells was performed to evaluate the toxicity of glucosamine sulfate at various concentrations.

Results: Molecular docking results revealed that glucosamine sulfate has a good binding affinity and stable interactions with MMP-3, MMP-9, and IL-4, indicating that it may have inhibitory effects on targeted genes. Nevertheless, the cell viability assay analysis demonstrated that glucosamine sulfate had considerable toxic effects in RAW 264.7 cells at highest concentrations.

Conclusions: Glucosamine sulfate exhibited stable molecular interactions with genes associated to OA development. However, GS toxicity at high concentrations necessitates future research studies to optimize dosing and assess its therapeutic safety in OA treatment.

Objectives: To explore pain outcomes in patients prescribed hydrocodone and psychotropic medications with or without CYP2D6 inhibition activity.

Methods: Patients hospitalized for lower/limited upper extremity injuries who were prescribed hydrocodone alongside a psychotropic medication were considered for this study (n=224). A subset of these patients (n=178) was prescribed a psychotropic medication known to inhibit CYP2D6, while the remainder (n=46) were prescribed psychotropic medications without CYP2D6 inhibition activity. Patient demographics and pain outcomes were collected by electronic health record review and interviews.

Results: Patients taking a psychotropic inhibitor of CYP2D6 exhibited longer duration of opioid use post-discharge (median 33 days [IQR 10-99]) compared with patients taking a psychotropic non-inhibitor (4 days [2-20], p<0.001). No significant differences were observed with in-hospital pain outcomes, including total dose of hydrocodone administered, duration of hydrocodone use, pain index scores, and the occurrence of common mild/moderate/severe hydrocodone side effects.

Conclusions: Patients prescribed at least one psychotropic inhibitor of CYP2D6 were more likely to continue using hydrocodone for up to 3 months following surgery. Knowledge of these critical drug-drug interactions could enhance clinical practice and improve patient outcomes. This study highlights negative post-operative pain outcomes in patients prescribed hydrocodone alongside a psychotropic inhibitor of CYP2D6. The results of this study indicate that patients taking psychotropic medications that inhibit CYP2D6 are at increased risk for prolonged hydrocodone use following orthopedic surgery.

Objectives: While the existing literature extensively covers the topic of tacrolimus variability, it remains crucial to gather data that are tailored to the Tunisian population. Our primary goal was to assess the variability in tacrolimus bioavailability using the Cp(0)/weight dosage ratio in Tunisian kidney transplant patients. We also aimed to determine the correlations between blood trough level (Cp(0)) and the area under the concentration-time curve (AUC0-12 h) in this cohort.

Methods: This retrospective study included patients treated with oral tacrolimus for the prevention of organ rejection between 2009 and 2023. The correlation between parameters was analyzed through a Pearson coefficient and a regression model. We assessed the inter- and intraindividual variability by calculating the coefficient of variation for patients with at least three samples.

Results: Analysis of 2,124 samples revealed a weak correlation (R=0.121) between Cp(0) and weight dosage. We found that 79.3 % of patients exhibited high variability in the Cp(0)/weight dosage ratio. A strong correlation (R=0.797) was found between Cp(0) and the AUC0-12 h. We also found that 47.6 % of patients showed high variability in the AUC0-12 h/Cp(0) ratio.

Conclusions: This study underscores the necessity for individualized therapeutic drug monitoring in Tunisian kidney transplant recipients due to the high variability in the Cp(0)/weight dosage ratio. The AUC0-12 h/Cp(0) ratio is proposed as a more consistent parameter for therapeutic drug monitoring, offering potential improvements in tacrolimus therapy management.

Objectives: Exercise capacity is decreased in diabetes mellitus due to impaired insulin sensitivity, endothelial dysfunction and mitochondrial dysfunction. The aim of the study was to evaluate the effect of metformin on exercise capacity in treatment naïve patients with type 2 diabetes mellitus.

Methods: Newly diagnosed type 2 diabetes mellitus patients were tested for baseline insulin resistance and exercise capacity, before starting on metformin. Exercise capacity was measured by incremental exercise testing in treadmill (ZAN 600 CPET system) using modified Bruce protocol at baseline, 6 weeks and 12 weeks following metformin therapy.

Results: A total of 33 treatment naïve type 2 diabetes patients were enrolled of which 19 patients completed the study. There was no significant change in any of the exercise capacity parameters at the end of 12 weeks of metformin. Nevertheless, there was a significant improvement in VO₂/kg among those with insulin resistance as compared to those without insulin resistance.

Conclusions: Metformin monotherapy did not produce any change in exercise capacity in treatment naïve type 2 diabetes patients. However, a significant fall in exercise capacity (VO₂/kg) was observed in patients without insulin resistance as compared to those with insulin resistance at the end of 12 weeks of metformin therapy.

The CYP2C19 enzyme is implicated in the metabolism of several clinically used drugs. Its phenotype is usually predicted by genotyping and indicates the expected enzymatic activity for each patient. However, with a few exceptions, CYP2C19 genotyping has not resulted in a reliable prediction of the metabolizer status, since most of the evidence currently available for this prediction comes from research into populations of predominantly European ancestry. Therefore, this review discusses the main factors that may alter the expected phenotype, as well as the urgent need to include ethnically diverse populations in further studies, so that, in the long term, it is possible to establish guidelines appropriate to these groups.

Objectives: Vernonia amygdalina Del. is a perennial tropical shrub from Asteraceae. The fresh leaf of V. amygdalina is consumed as a vegetable due to its medicinal and nutritional properties. The present study focused on the quantification of bioactive compounds, luteolin-7-O-glucoside, luteolin-7-O-glucuronide, and 1,5-O-dicaffeoylquinic acid from aqueous leaf extract of V. amygdalina. The study also aims to investigate the effects of the aqueous leaf extract of V. amygdalina on cytochrome P450 2C9 (CYP2C9), and cytochrome P450 3A4 (CYP3A4) in hepatic cells of control and diabetic rats.

Methods: The quantification of the bioactive compounds was conducted using ultra-high-performance liquid chromatography multiple reactions monitoring tandem mass spectrometry (UHPLC-MS/MS-MRM) technique. The effect of the extract on CYP2C9 and CYP3A4 activities was determined using a fluorometric screening kit according to the manufacturer's instructions.

Results: The three bioactive compounds were detected and quantified in the aqueous leaf extract. Results showed that the content of luteolin-7-O-glucuronide (47 μg/mg) was the highest followed by luteolin-7-O-glucoside (3.5 μg/mg) and 1,5-O-dicaffeoylquinic acid (1.07 μg/mg). The extract showed an inhibitory effect on CYP3A4 and CYP2C9 enzyme activities in control and diabetic rats.

Conclusions: The UHPLC-MS/MS-MRM method is sensitive and reliable for the quality control of V. amygdalina leaf extract. The inhibitory effect of the extract suggests that concomitant use of V. amygdalina leaf preparations with conventional drugs metabolized and eliminated from the body by CYP3A4 and CYP2C9 enzymes may lead to possible interaction.

Introduction: Pharmacogenetics (PGx) has the potential to improve patient care, allowing to transform medical interventions by providing personalized therapeutic strategies. Scientific evidence supports the use of PGx in clinical practice and international organizations are developing clinical guidelines to facilitate the utilization of PGx testing. However, clinical implementation of PGx is limited and unequal worldwide.

Content: This review summarizes regional and national Spanish initiatives to implement PGx in the clinical practice.

Summary and outlook: Diverse strategies to implement PGx in healthcare are applied across countries or even in the different regions of a specific country. Such was the case of Spain, a European country with 17 Autonomous Regions and two Autonomous Cities, each one with capacity to manage their own healthcare systems. Nevertheless, during the past years, many initiatives and strategies have been launched in Spain to develop different aspects of PGx. Importantly, the National Healthcare System has approved a PGx testing catalogue. This review highlights the crucial work and efforts of scientific societies (like the Spanish Society of Pharmacogenetics and Pharmacogenomics), of experts in PGx, of healthcare providers and of governmental parties in the implementation of PGx to personalize patient therapy, focused in Spain.