Journal of Clinical Pharmacy and Therapeutics最新文献

Purpose. Catechol-O-methyltransferase (COMT) participates in the regulation of dopaminergic and adrenergic neurotransmission. COMT Val158Met polymorphism influences the efficacy and safety of opioids, but its association with oxycodone treatment in patients with cancer pain is yet to be elucidated. Hence, this study aimed to investigate the influence of COMT Val158Met polymorphism on oxycodone requirements, drug adverse effects, and pain sensitivity in patients with cancer. Methods. Patients with moderate to severe cancer pain treated with oxycodone were enrolled, of which 101 patients completed the study. All patients were genotyped for COMT Val158Met polymorphism using DNA from blood samples and were categorized into the wild-type group (n = 50) comprising individuals with the Val/Val genotype and the mutant group (n = 51) encompassing those with the Val/Met or Met/Met genotype. Numerical rating scale (NRS) scores, oxycodone requirements, and the incidence of oxycodone-related adverse drug reactions were compared between the two groups. Results. Patients in the mutant group exhibited higher NRS scores (6.18 ± 1.40) before the oxycodone treatment than those in the wild-type (5.48 ± 1.54) group (P = 0.017). Patients in the wild-type group required more oxycodone (96.00 ± 146.19 mg/24 h) than those in the mutant (77.25 ± 83.91 mg/24 h) group (P = 0.0365). The incidence rates of dysuria (2.0% vs. 16.0%, P = 0.016) and fatigue (0.0% vs. 12.0%, P = 0.013) were significantly lower in the mutant group than those in the wild-type group. Moreover, patients with at least one Met allele showed a lower risk of suffering from oxycodone-related side effects than those with the wild homozygote (41.2% vs. 68.0%, P = 0.007). Conclusion. Genetic variations in the COMT Val158Met gene may contribute to variability in the efficacy and safety of oxycodone in cancer pain treatment. The findings from this study emphasize the potential of pharmacogenetics in personalizing pain management. Furthermore, oxycodone therapeutic strategies can be designed based on genetic polymorphisms.

Background. Nasopharyngeal carcinoma (NPC), prevalent in East Asia and associated with EBV infection, poses unique challenges due to its complex immunological interactions. This study aims to dissect the molecular and immune mechanisms of NPC, providing a pathway to novel treatments. Methods. Through bioinformatics, we analyzed gene expression and immune cell infiltration in NPC tissues. Differential gene expression profiling, single-cell RNA sequencing, and gene set variation analysis (GSVA) were performed to understand the immune landscape and identify EBV-related molecular changes. Results. The differential gene expression analysis highlighted a diverse immune cell composition, suggesting an intricate immune evasion landscape. GSVA pinpointed pathways linked to tumor immunity and EBV pathogenesis. Notably, the expression of immune checkpoints, such as PD-L1, was significantly associated with NPC, offering a potential target for immunotherapy. Conclusions. Our findings underscore the potential of immunotherapeutic approaches in NPC, particularly those modulating the PD-1/PD-L1 axis. The integration of bioinformatics and immunology in NPC research provides a foundation for personalized medicine and warrants further exploration into combination therapies to enhance treatment efficacy.

Aims. This study aimed to identify and analyze the factors significantly influencing long-term insulin medication adherence among outpatients and to evaluate whether pharmaceutical interventions targeting these factors can improve patient medication adherence and glycemic control. Methods. A cohort of 180 patients was recruited from a tertiary hospital in Nanjing, China. Factors potentially influencing insulin adherence were scrutinized employing the KAP (knowledge, attitude/belief, and practice) health behavior model. Baseline characteristics were extracted from the hospital information system, while patient knowledge of the disease and medication, medication adherence, medication beliefs, and management self-efficacy were assessed, respectively, using self-developed questionnaires, MMAS-8, C-DMSES, and BMQ scales. Univariate and multivariate analyses were conducted to determine the impact of these factors on insulin adherence. Following this, participants were randomly allocated to either the intervention or control group. The intervention group received three months of weekly telephone sessions and educational interventions targeting facets such as medication knowledge and beliefs, while the control group received standard care. After the intervention, insulin adherence and glycemic control conditions of both groups were collected and re-evaluated. Results. After excluding lost-to-follow-up patients, 152 individuals were analyzed (intervention: 75 and control: 77). Multivariate analyses revealed factors influencing insulin adherence, including age, diabetes duration, health insurance status, HbA1c level, disease and medication knowledge, diabetes management self-efficacy, and medication beliefs (P < 0.05). Before targeted pharmaceutical care, no significant differences existed in insulin adherence, HbA1c levels, management self-efficacy, knowledge, or medication beliefs between intervention and control groups (P > 0.05). However, subsequent pharmaceutical intervention notably improved adherence, HbA1c levels, self-efficacy, knowledge, and medication beliefs (P < 0.05). Conclusion. This study examines the impact of glycemic control, health insurance status, management self-efficacy, level of knowledge, and medication beliefs on improving insulin medication adherence in patients with type 2 diabetes mellitus. Targeted pharmaceutical intervention can enhance medication adherence, improve glucose control, and promote rational insulin use. This trial is registered with ChiCTR2300074444.

Purpose. To evaluate the bioequivalence of two different tofacitinib citrate tablets formulations among healthy Chinese subjects under fasting and fed conditions and to observe the safety of test preparation and reference preparation in healthy subjects. Method. This randomized, open-label, 2-period, crossover, bioequivalence study included 64 healthy Chinese subjects (fasting: n = 32, fed: n = 32). The subjects were assigned to receive a single 5-mg dose of the test or a reference tofacitinib citrate tablets. Blood samples were collected at predose and up to 24 hours after dosing. Area under the plasma concentration time curve from zero to the last measurable concentration (AUC_0-t), the area from time zero to infinite (AUC_0-∞), and maximum plasma concentration (C_max) were used for bioequivalence assessment. Safety assessment was conducted by vital signs, physical examination, laboratory examination, and 12-lead electrocardiogram during the study, from the time the subject receiving the test drug to the end of the last visit. Results. Under fed condition, the 90% CIs of the geometric mean ratios of the test/reference for tofacitinib citrate tablets were 98.40–104.16% for AUC_0-t, 89.96–116.70% for C_max, and 98.50–104.15% for AUC_0-∞. Under fasting condition, the 90% CIs of the geometric mean ratios of the test/reference for tofacitinib citrate tablets were 93.65–101.60% for AUC_0-t, 90.06–109.15% for C_max, and 93.88–101.51% for AUC_0-∞. There were no serious events. Conclusion. The 90% CI for the geometric mean ratio (test/reference) of C_max, AUC_0-t, and AUC_0-∞ were within the range of 80.00%–125.00%, indicating that the test formulation was equivalent to the reference formulation in healthy Chinese subjects under both fasting and fed conditions. They are similar in terms of safety. This trial is registered with CTR20190366.

Background. Preeclampsia (PE) is a common obstetric disorder hallmarked by impaired trophoblast invasion and a skew toward an inflammatory immune response. Echinatin, a flavonoid with established anti-inflammatory, antioxidant, and anticancer activities, may offer therapeutic benefits in PE. Our study aimed to investigate the effect of echinatin on preeclampsia in vitro and in vivo and to reveal the potential molecular mechanism of its action. Methods. Eighteen adult female Sprague Dawley rats were randomized into three experimental groups: a PE model group, a PE + echinatin treatment group, and a PE + echinatin treatment group with TLR4 overexpression. Placental tissue CK7 expression was assessed by immunohistochemistry. TUNEL immunofluorescence staining quantified placental cell apoptosis. Cell viability, proliferation, and migration were evaluated using cell counting kit-8, EdU incorporation, and Transwell assays, respectively. Oxidative stress parameters of malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured. Flow cytometry determined cell apoptosis and intracellular reactive oxygen species (ROS) levels. Western blotting evaluated the expression of proteins related to the TLR4-MyD88-NF-κB signaling pathway, and the concentrations of TNF-α, IL-6, and IL-18 were measured with ELISA kits. Results. Echinatin mitigated placental damage, reduced apoptosis, and increased CK7 expression. It significantly enhanced HTR-8/SVneo cell viability and migration. Echinatin also counteracted H₂O₂-induced ROS production and cell death in HTR-8/SVneo cells. Moreover, it inhibited the expression of proteins within the TLR4-MyD88-NF-κB signaling cascade. Overexpression of TLR4 negated echinatin’s protective effects. Conclusion. Echinatin exerts protective effects against oxidative stress and inflammation in PE by targeting the TLR4-MyD88-NF-κB pathway, suggesting its therapeutic potential for the management of preeclampsia.