Journal of Pharmacy and Pharmaceutical Sciences最新文献

Objective: Tacrolimus-mycophenolic acid (MPA)-prednisolone immunosuppression remains the first-line management of kidney transplantation. Despite this, a switch to low-dose tacrolimus in combination with an mTOR inhibitor may be inevitable in some patients due to various factors. This study aims to identify the reasons and factors influencing the switch of tacrolimus-MPA to other combination immunosuppressive agents among kidney transplant recipients (KTRs).

Methods: This retrospective observational cohort study included adult KTRs between year 2011-2019 at the two main kidney transplant centers in Malaysia. Demographic data, clinical, laboratory and medication information were collected. Multiple logistic regression was used to determine factors associated with the initial switch of tacrolimus-MPA immunosuppressive therapy.

Results: From the 257 KTRs studied, 81 KTRs had their immunosuppressive agents switched from tacrolimus-MPA-prednisolone immunosuppressive regimen, with majority (96.3%, n = 78) switching to everolimus, an mTOR inhibitor in combination with low-dose tacrolimus. The average time switch was 125.8 ± 100.9 days. The main reasons for the initial switch include unresolved transaminitis (n = 15, 18.5%), cytomegalovirus (CMV) infection (n = 13, 16.0%) and BK virus (BKV) infection (n = 10, 12.3%). In the multiple logistic analysis, Malay ethnicity (P < 0.001), KTRs without post-transplant hypertension (P = 0.004) and KTRs with BKV infection (P < 0.001) were predictors for the initial switch of tacrolimus-MPA-prednisolone immunosuppressive therapy.

Conclusion: Early identification of factors associated with the switch may prepare healthcare professionals for KTRs risk stratification, allowing ample time for appropriate optimization of tacrolimus-MPA-prednisolone immunosuppressive therapy based on individual patient's needs. This can possibly be a cost-effective alternative to switching to mTOR inhibitors for improved transplant outcomes.

[This corrects the article DOI: 10.3389/jpps.2024.13210.].

Pharmacogenomic (PGx) research investigates how an individual's genetic make-up impacts their drug metabolism. PGx testing can therefore inform therapeutic decision-making, especially as compelling evidence develops over time to substantiate its clinical and personal utility across a range of therapeutic areas. PGx biomarker CYP2D6, in particular, is widely implicated in drug metabolism and across several therapeutic areas. Real-world evidence (RWE) derived intentionally using electronic health record (EHR) and insurance claims data presents an opportunity to explore clinical-behavioral outcomes and implementation barriers and facilitators for PGx testing in real-world clinical settings. In this systematic review, we explored these areas with a focus on PGx biomarker CYP2D6, investigating drug-gene pairs with strong evidence (Level A, Final classification by the Clinical Pharmacogenetics Implementation Consortium [CPIC]). Across 25 studies that met our study inclusion criteria, nine (9) drug-gene pairs that met the CPIC Level A, Final, strong evidence category for CYP2D6 were described. Overarching qualitative themes across studies were 1) variation in CYP2D6 biomarker testing and interpretation, and 2) PGx test implementation and data considerations. CYP2D6-drug pairs were reported across four therapeutic areas (analgesia [n = 21], psychiatry [n = 17], oncology [n = 7], gastroenterology [n = 6]) with the two most researched drugs being codeine (n = 21) and tramadol (n = 18). Six (6) of 25 articles reported PGx clinical outcomes, considered to be a "measurable change in symptoms, overall health, ability to function, quality of life, or survival outcomes" in relation to PGx testing. Special EHR and claims data considerations for future work include but are not limited to addressing inconsistent phenotype categorizations (i.e., natural genotype versus phenoconversion); lack of reliable racial, ethnic, and genetic ancestry data within EHR and claims data sources; and data inoperability issues between PGx test results and EHRs.

Introduction: Tiotropium, a long-acting muscarinic antagonist, is commonly employed for the maintenance treatment of chronic obstructive pulmonary disease (COPD) and asthma. While its efficacy has been validated through numerous randomized controlled trials, safety concerns in real-world post-marketing settings necessitate further evaluation.

Aim: This study aimed to analyze the adverse events (AEs) associated with tiotropium reported in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database to identify potential safety signals.

Methods: A retrospective analysis was conducted on adverse reaction reports related to tiotropium in the FAERS database from the first quarter of 2004 to the fourth quarter of 2024. The AE names in the FAERS database were systematically classified using the Preferred Terms (PTs) and System Organ Classes (SOCs) provided by the latest version of the Medical Dictionary for Regulatory Activities (MedDRA 27.1). After deduplication, a combination of methods, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS), was employed for disproportionality analysis.

Results: A total of 129,763 AE reports related to tiotropium were included in the analysis, affecting 65,045 patients. These reports encompassed 27 different SOC categories, identifying 264 AEs associated with tiotropium. After excluding certain AEs deemed clinically insignificant, the most common AEs reported were dyspnea (n = 8,600), cough (n = 2,440), and pneumonia (n = 2080). The AEs exhibiting the highest signal strength included aggravated dyspnea (ROR: 162.04), hoarseness (ROR: 43.42), and aggravated chronic obstructive airway disease (ROR: 43.17). Additionally, we identified potential risks not mentioned in the instructions (United States Prescribing Information and the Canadian Product Monograph), such as epiglottic cancer, halo vision, and malignant lung tumors.

Conclusion: This study offers a more comprehensive understanding of tiotropium by uncovering previously unreported adverse reactions. Physicians should take these newly identified adverse reactions into account when prescribing this medication.

Object: The development of cognitive-enhancing drugs from Ginkgo biloba extract is actively pursued worldwide. This study compares the chemical compositions of different G. biloba extracts and their formulated drugs, highlighting the distinguishing characteristics and potential benefits of optimized G. biloba extract, EGb 761^®.

Methods: We analyzed three G. biloba extracts and fifteen formulated drugs using HPLC, principal component analysis, and LC-MS/MS to identify key compositional differences. Molecular docking analysis was conducted to evaluate the binding affinity of the key component with a target protein involved in cognitive enhancement. CYP inhibition assays were performed on selected extracts and their derived products to examine drug-drug interactions.

Results: EGb 761^® and its formulated drugs displayed a unique composition, characterized by a significantly higher level of protocatechuic acid (PCA). PCA demonstrated strong interactions with the M₁ receptor, acetylcholinesterase, glycogen synthase kinase-3, which are the key targets for cognitive enhancement. CYP inhibition assays indicated that EGb 761^® and the drugs derived from EGb 761^® had lower inhibitory activity compared to other samples.

Conclusion: The high PCA content in EGb 761^® may contribute to cognitive benefits. With low CYP inhibition, it suggests minimal interference with drug metabolism, highlighting its potential as a safer cognitive enhancer. Ultimately, this study indicates that the composition of EGb 761^® can be effectively leveraged for its pharmacological benefits.

Introduction: Patient Support Programs (PSPs) are growing globally to support early reimbursement, disease and medication dosing management. In Canada, the lack of public health support has promoted the rapid expansion of company-supported disease-specific or drug-product-specific PSPs. Data collected from these programs generate unique Canadian data serving as a valuable source of real-world data (RWD), generally adopted in EU and US as a source of evidence generation. This review evaluates the suitability of PSP data for regulatory or reimbursement submissions, based on recently published Real World Evidence guidelines by the Canadian Drug Agency (CDA-AMC).

Methods: Peer-reviewed publications evaluating patients with chronic diseases enrolled in a PSP from 1 January 2020, to 31 March 2025, were selected for review. The checklist in the CDA-AMC RWE Guideline was used to measure the quality and suitability of the PSP data.

Results: Nine studies were reviewed against the checklist. Based on the criteria required to inform decision-making, most studies failed to meet key criteria for regulatory submissions. One recently published study, "Therapeutic Drug Monitoring of Infliximab" met most regulatory and reimbursement submission requirements.

Conclusion: Data quality validation, data source transparency, validated methodology to manage study bias, measured or unmeasured confounders, and robust outcome analysis, including sensitivity and quantitative bias analysis, are essential to ensure PSP data analysis results in successful decision-making.

Objective: To analyze the impact of a Transformative Learning Theory (TLT)-based toolkit on pharmacy students' self-evaluation of professional identity formation (PIF).

Methods: This prospective, interventional cohort study included pre-clinical pharmacy students in a hospital skills-based course. Study participants were included if they completed the Professional Self Identity Questionnaire (PSIQ-9) and Macleod Clark Professional Identity Scale (MCPIS-9) at baseline (week 1), midpoint (week 8), and endpoint (week 15) of the course. The primary outcome was to assess the mean change in PSIQ-9 and MCPIS-9 scores from baseline to endpoint; the outcome was analyzed using the Wilcoxon-Signed Rank Test. Secondary outcomes included assessing the mean difference in questionnaire scores from baseline to midpoint and midpoint to endpoint.

Results: Seventy-nine pharmacy students were eligible, with 11 (14%) completing both questionnaires at all time points and 39 (49%) completing them at baseline and midpoint. Comparing baseline and endpoint scores, there was an increase in the PSIQ-9 mean difference for teaching others and a decrease in the MCPIS-9 for feeling ashamed of the profession. No MCPIS-9 differences were found between baseline and midpoint. Three PSIQ-9 questions, communication, using patient records, and teaching others, were significant at baseline and midpoint.

Conclusion: The TLT-based toolkit had a minimal impact on students' self-evaluation of PIF based on the PSIQ-9 and MCPIS-9 questionnaires over a 15-week course. Studies with larger sample sizes and longer durations are needed to provide more conclusive results.

Objective: This study evaluated the use of stress ulcer prophylaxis (SUP), assessed the costs associated with inappropriate use, and highlighted the impact of clinical pharmacists on improving adherence to the SUP guidelines.

Method: A prospective, non-randomized controlled study was carried out in two intensive care units (ICUs) of a training and research hospital between 1 June 2023 and 1 December 2023. Routine care services were provided for the observation group (OG) patients. In the guideline group (GG) patients, SUP management and routine care were performed according to ASHP guidelines. The physician and clinical pharmacist jointly evaluated the patients to determine the suitability of their SUP indications. Adherence rates to ASHP guidelines and the costs associated with nonadherence were evaluated.

Results: A total of 196 patients were included in the study: 121 in the OG and 75 in the GG. A total of 54.6% of the patients were male, and the reason for hospitalization was mainly surgery (52.6%). SUP use was higher in OG (100%) than in GG (42.6%) (p < 0.001). The indication rate according to the ASHP guidelines was significantly higher in the GG group (100%) than in the OG group (54.5%) (p < 0.001). Dosage form adherence was significantly lower in the OG (0%) than in the GG (100%) (p < 0.001). The costs associated with proton pump inhibitor use for inappropriate indications and incorrect dosage forms were $60 versus $0 (p < 0.001) and $321 versus $0 (p < 0.001) in OG and GG, respectively. Overall, cost savings of $327 were achieved in the GG group.

Conclusion: Inappropriate SUP use is common in the ICUs. Adequate adherence to guidelines and proactive involvement of clinical pharmacists may reduce inappropriate SUP in ICUs and the associated costs.

This study focuses on implementing a composition of the natural flavonoid dihydroquercetin (DHQ) with L-lysine in the treatment of thermal burns. The wound-healing activity of DHQ is well-known. The addition of amino acid to the composition increases the water solubility of the flavonoids, providing an opportunity to develop a spray dosage form. The research involved 60 male Wistar rats divided into five treatment groups. Sea buck oil served as a positive control. On day 14, the composition treatment group showed significant progress in wound healing, being 9.6 ± 2.0% ahead of the other groups in absolute terms. On day 35, treatment with the composition resulted in a significant decrease in relative wound area to 1.9 ± 0.9%, while in the negative and positive control groups, it was 10.7 ± 7.8% and 8.4 ± 4.9%, respectively. At the same time, the epidermal and dermal layers were found to be clearly distinguished in the composition treatment according to histological analysis. Numerous collagen fibres were clearly visible, and the active process of keloid scar formation was observed. An additive effect of the combined use of DHQ and L-lysine was observed (F = 0.21, p = 0.649). A natural next step is to develop the dosage form for the DHQ-L-lysine composition.