International journal of clinical pharmacology and therapeutics最新文献

Objective: To evaluate the pharmacokinetics (PK), safety, and bioequivalence of two formulations of apixaban in healthy Chinese subjects under fasting and fed conditions.

Materials and methods: A single-center, randomized, open, single-dose, two-period crossover PK study was carried out under fasting and fed conditions in 64 healthy subjects enrolled in either the fasting (36 subjects) or the fed (28 subjects) arms of the study. Subjects received a single oral dose of 2.5 mg apixaban tablets as test (T) or reference (R) formulation. The primary PK parameters determined were the area under the plasma concentration-time curve from zero to t and ∞ (AUC_0-t and AUC_0-∞) and the maximal plasma concentration (C_max). Safety was assessed mainly from the occurrence of adverse events (AEs).

Results: A single drop-out in the fed arm of the trial was excluded from the statistical evaluation. The 90% confidence intervals (CIs) for the geometric mean ratio (GMR) for T/R using AUC_0-t were 95.4 - 100.9% and 97.8 - 103.8%, and for AUC_0-∞ were 95.3 - 100.6% and 98.3 - 104.3% under fasting (36 subjects) and fed (27 subjects) conditions, respectively. Similarly, the 90% CIs for C_max were 94.6 - 103.1% and 88.8 - 102.0% under fasting (36 subjects) and the fed (27 subjects) conditions, respectively. Therefore, the 90% CIs for the T/R AUC and C_max ratios were within the standard range for bioequivalence (80.0 - 125.0%). There were no serious adverse events (SAEs).

Conclusion: The test and reference 2.5 mg apixaban tablets were bioequivalent and both showed good tolerability and safety.

Objectives: This study aimed to determine the effectiveness of analgesics in inhibiting cancer development in patients with diabetes based on a sample cohort supplied by the Korean National Health Insurance Service.

Materials and methods: Regular users of analgesics included those using prescription analgesics ≥ 15 days per month at least 6 times over 2 years after the diagnosis of diabetes mellitus (baseline). The effectiveness of analgesics in patients with diabetes was evaluated using metformin adherence and three models: model 1 was adjusted for age and sex; model 2 was further adjusted for body mass index (BMI), exercise, cholesterol, hypertension, and Charlson comorbidity index (CCI); and model 3 was further adjusted for analgesics.

Results: Based on stringent extraction criteria, the sample had a cancer incidence of 4.6%. The hazard ratios of models 1 and 2 were 0.830 and 0.865, respectively. The adjusted hazard ratio for all variables, including acetaminophen and nonsteroidal anti-inflammatory drugs such as aspirin and ibuprofen, was 0.871 (model 3).

Conclusion: Regular use of analgesics by patients with diabetes decreased their risk of subsequent cancer development in this large national cohort. Compared with participants who did not develop cancer, those with cancer were older and more likely to be male, did not exercise, have more comorbidities (as assessed by CCI), and did not use analgesics regularly.

Purpose: Coronavirus disease 2019 (COVID-19) has emerged as a serious threat to public health; anticancer-repositioning treatment strategy has been formulated to treat the disease. However, evidence supporting the efficacy and safety of repositioned anticancer treatment in treating COVID-19-infected non-cancer patients (CINPs) is limited. Therefore, this study analyzed published randomized controlled trials (RCTs) evaluating the impact of anticancer drugs compared to current standards of care (SOCs) on CINP treatment.

Materials and methods: The PubMed and Embase databases were searched to identify eligible RCTs. Outcome measures included mortality, the use of mechanical ventilation (MV), and serious adverse events (SAEs).

Results: 25 RCTs were reviewed in our study. Compared to SOCs, repositioned anticancer therapy for treating CINPs was associated with mortality reduction (odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.65 - 0.94, p = 0.01). Using the repositioned anticancer treatment exhibited statistically significant reduction, in both the number of CINPs using MV (OR = 0.67, 95% CI = 0.51 - 0.88, p = 0.004) and experiencing SAEs (OR = 0.79, 95% CI = 0.69 - 0.91, p = 0.0009).

Conclusion: Conclusively, repositioned anticancer treatment was shown significant differences from SOCs in treating CINPs, which appears to be more associated with mortality, MV use, and SAE development reduction in CINPs.

Background: Dysbiosis (also called dysbacteriosis) is characterized by a disruption of the microbiome, resulting in an imbalance in the microbiota, changes in their functional composition and metabolic activities, and a shift in their local distribution. Dysbiosis is most commonly reported as a condition affecting the gastrointestinal tract, for example with bacterial or fungal overgrowth in the small intestine. Known causes of dysbiosis include antibiotic use, liver disease, and alcohol misuse.

Aims: To determine those variables associated with the diagnosis of dysbiosis using a national database containing data supplied by general practitioners in Germany.

Materials and methods: Patient data for the period January 2005 to December 2018 were obtained from the Disease Analyzer database (IQVIA) based on data from 1,193 general practices in Germany. Inclusion criteria were all adult patients (≥ 18 years) with an initial diagnosis of dysbiosis documented anonymously. Data for variables such as drug treatment, other diseases etc. associated with the diagnosis were analyzed using multivariable logistic regression analyses.

Results: A total of 4,013 patients diagnosed with dysbiosis and a comparative control cohort of 4,013 patients without such a dysbiosis were included in the study. The mean age in both groups was ~ 50 years where 65.2% of subjects were women. Decongestants and other nasal preparations for topical use (OR: 1.45, 95% CI: 1.14 - 1.85), proton pump inhibitors (OR: 1.39; 95% CI: 1.21 - 1.61), and systemic antibiotics (OR: 1.28, 95% CI: 1.13 - 1.47) were significantly associated with an increased occurrence of dysbiosis, whereas non-steroidal antirheumatic drugs (OR: 0.78, 95% CI: 0.69 - 0.87), lipid-lowering drugs (OR: 0.76, 95% CI: 0.63 - 0.93), and ACE inhibitors (OR: 0.64, 95% CI: 0.53 - 0.77) were associated with a decreased occurrence of dysbiosis.

Conclusion: The study provides evidence that treatment with decongestants and other nasal preparations is strongly associated with an increased occurrence of dysbiosis. Although the pathophysiology of dysbiosis is multifactorial and confounding factors cannot be ruled out, the close correlation seen may have clinical significance.

Objective: To investigate the differences and their clinical significance in the intestinal microbiota in patients with Parkinson's disease (PD) in comparison to those in healthy controls.

Materials and methods: 20 patients with PD who received treatment in the First Affiliated Hospital of Bengbu Medical College between January 2019 and December 2019 were selected as the research subjects to form the PD group, while 20 age- and gender-matched healthy volunteers were selected as the control group. Fecal samples from the two groups were collected, and the V4 region of 16S-ribosomal ribonucleic acid was selected for high-throughput sequencing analysis to explore any differences, as well as their significance, in the intestinal microbiota abundance at the class, family, and genus levels between the two study groups.

Results: The operational taxonomic unit cluster analysis revealed a high degree of overlap between the patients with PD and the controls. Compared with the controls, the relative abundance of Coriobacteriia and Coriobacteriaceae was increased in the PD group (p < 0.01), while the relative abundance of Lachnospiraceae was significantly lower (p < 0.01). The relative abundance of Collinsella, Escherichia, and Fusobacterium in the PD group was significantly higher than in the control group (p < 0.05).

Conclusion: Compared with the healthy subjects, the abundance of specific microflora was significantly different in the PD patients at the class, family, and genus level. Intestinal flora may act as a potential biomarker for PD and provide a theoretical basis for microflora transplantation therapy.

Objective: This retrospective analysis was to examine the efficacy and safety of belimumab in lupus nephritis in China.

Materials and methods: 25 patients who were regularly followed up every 3 months in our hospital in China were included. All patients were diagnosed as having lupus nephritis and received belimumab to complement standard therapy. The primary outcomes 24-hour proteinuria, complement level, estimated glomerular filtration rate (eGFR), SELENA-SLEDAI scores, prednisone daily dose, and adverse reactions were recorded at 12, 24, 36, and 48 weeks.

Results: The SELENA-SLEDAI scores and 24-hour urine protein of the 25 patients decreased visibly from baseline 15.96 ± 3.02, 1.52 ± 1.72 to 9.52 ± 2.66 (p < 0.01), 0.5 ± 0.2 (p < 0.05) at 48 weeks, the eGFR of the 25 patients increased from 76.45 ± 22.2 to 85.48 ± 19.26 (p < 0.01) at 48 weeks, complement levels also showed a trend to increase. One patient experienced renal flare at 48 weeks, and the level of the patient's 24-hour proteinuria had been > 0.7 g at 6 months; this may be a strong predictive factor for further renal response at 12 months. Belimumab added to the standard therapy also improved the hematologic complications caused by systemic lupus erythematosus in 2 patients with a lower glucocorticoid dose. There were no serious adverse events.

Conclusion: Belimumab may be effective and safe in lupus nephritis even with regard to hematologic complications.

Aims: The aims of this study were to evaluate and compare the pharmacokinetic profiles and bioequivalence of two tablet formulations of methylprednisolone (test formulation: Zhejiang Xianju Pharmaceutical Co., Ltd., China; reference formulation: Medrol, Pfizer Italia SRL) in healthy Chinese subjects under fasting and fed conditions.

Materials and methods: Subjects were randomly allocated to either the fasting group or the fed group and also to one of two sequences (test-reference or reference-test), according to which they received a single 16-mg dose of the test or reference methylprednisolone tablet in the study periods. Blood samples were collected pre dose and at intervals up to 16 hours after administration. Plasma methylprednisolone concentrations were determined using a validated liquid chromatography tandem mass spectrometry method. The safety of the medications was monitored throughout the study. The primary pharmacokinetic parameters measured were C_max, AUC_0-t, and AUC_0-∞.

Results: A total of 56 subjects were enrolled, and all completed the study. The 90% confidence intervals for C_max, AUC_0-t, and AUC_0-∞, measured under both fasting and fed conditions, fell within the acceptable range for bioequivalence of 80 - 125%. Analysis of variance showed that there were no significant differences in the primary pharmacokinetic parameters (C_max, AUC_0-t, and AUC_0-∞) between the test and reference formulation measured under both fasted and fed conditions. No serious or unexpected adverse drug reactions occurred during the study period.

Conclusion: The test methylprednisolone 16 mg tablet produced in China is bioequivalent to the reference formulation (Medrol) in healthy Chinese subjects measured under both fasting and fed conditions. Both formulations were well tolerated by all study participants.