International journal of clinical pharmacology and therapeutics最新文献

Objective: Our aim in this study is to investigate the advantages of a mobile personal digital assistant (PDA)-based anticoagulant abdominal injection positioning card in the subcutaneous injection process of low molecular weight heparin (LMWH).

Materials and methods: This was a historical control study. Convenience sampling was used to include 210 patients diagnosed with venous thromboembolism who received dalteparin sodium (Fragmin) injections in our department between January 2021 and December 2022. Patients were categorized into the control group and the experimental group based on the time period before and after the implementation of the PDA-based anticoagulant abdominal injection positioning card that was developed by the information research and development department of our hospital. The control group consisted of 105 patients treated before the introduction of the PDA-based card (January to December 2021), while the experimental group comprised 105 patients treated after its introduction (January to December 2022). Patients in the control group used subcutaneous injection positioning cards made of paper to determine injection sites, while those in the experimental group used the PDA-based cards to determine injection sites. Outcome measures, including the incidence of subcutaneous bleeding, time spent on the subcutaneous injection procedure, and patient satisfaction, were compared between the two groups.

Results: The incidence of subcutaneous bleeding was 5.59% in the experimental group vs. 5.61% in the control group, with no statistically significant difference between the two groups (p > 0.05). The time required for the subcutaneous injection was significantly shorter in the experimental group (63.11 ± 3.59 seconds) than in the control group (83.38 ± 6.96 seconds) (p < 0.05). The patient satisfaction rate was higher in the experimental group (94.3%) than in the control group (80.0%) (p < 0.05).

Conclusion: Use of the PDA-based anticoagulant abdominal injection positioning card to determine the abdominal subcutaneous injection site for LMWH does not increase the occurrence of adverse reactions of subcutaneous bleeding, and can ensure the accuracy of medication use and the safety of medication for patients, reduce the time of nursing operations, optimize the nursing process, and improve patient satisfaction.

Aims: To investigate the relationship between the neutrophil:lymphocyte ratio (NLR) in peripheral venous blood and the degree of vascular reflow following mechanical thrombectomy in patients with acute ischemic stroke (AIS) and anterior circulation large vessel occlusion.

Materials and methods: Patients with successful reflow were divided into two groups: i) partial reflow group (mTICI = 2b) and ii) complete reflow group (mTICI = 3) according to the modified thrombolysis in cerebral infarction classification (mTICI). Basic clinical data, disease characteristics, interventional therapy and prognosis for patients in the two groups were compared, and the association with the degree of postoperative reflow determined using multivariate logistic analysis.

Results: Univariate analysis of 21 cases of partial reflow and 45 cases of complete reflow showed statistically significant differences in the preoperative NLR, occluded vessel location, thrombus burden, puncture to recanalization time, thrombus removal times, and prognosis at 90 days post operation (p < 0.05 for all comparisons). Compared with patients with partial reflow, patients with complete reflow had lower NLR, more occluded vessels in the middle cerebral artery, lower thrombus burden, shorter operation time, fewer thrombectomy time and better clinical prognosis.

Discussion and conclusion: Multivariate logistic regression analysis thus shows that NLR and a low thrombus burden are independent prediction factors for complete reflow in this collective of AIS patients. Patients with anterior circulation AIS coupled with low NLR and low thrombus burden prior to mechanical thrombectomy are more likely to achieve complete reflow.

Objective: To present a case of encephalopathy after the administration of an iodinated contrast medium in a coronary angiography procedure.

Case summary: A 75-year-old male heart transplant recipient with cardiac allograft vasculopathy underwent coronary angiography followed by percutaneous coronary intervention. An iodinated contrast medium, ioversol, was used. Two hours later, the patient had focal impaired awareness seizure (unresponsive, head and gaze deviated to the left, with oroalimentary and gestural automatisms). Brain imaging showed no acute lesions or perfusion deficits. Electroencephalography revealed the focal slowing on the right fronto-temporal and left fronto-centro-temporal region, as well as paroxysmal discharges of high voltage delta activity (encephalopathic pattern). The patient was treated with intravenous levetiracetam. The symptoms completely resolved the next day, and the patient was discharged after 5 days of hospitalization.

Discussion: Contrast-induced encephalopathy (CIE) is an extremely rare complication of cardiac catheterization, with an incidence of 0.06%. Although the exact pathophysiology of this disorder is still not completely understood, it has been hypothesized that hyperosmolar contrast agent causes the shrinkage of endothelial cells, followed by the opening of tight junctions and the disruption of the blood-brain barrier resulting in direct neurotoxicity of the iodinated contrast medium.

Conclusion: CIE is a rare complication of cardiac catheterization, likely under-recognized and under-diagnosed due to its variable clinical features, unremarkable or nonspecific radiological findings, and a lack of well-defined diagnostic criteria. Despite the challenging diagnosis and a lack of evidence for treatment strategies, the prognosis is good with supportive therapy.

Objective: To determine the pharmacokinetic properties and bioequivalence of a reference doxorubicin injectable formulation (Caelyx) and the test formulation, a newly developed doxorubicin hydrochloride liposome injection formulation (LY01612), administered as single bolus doses in Chinese patients with advanced breast cancer.

Materials and methods: The study was multicentric, randomized, open-label, two-treatment, two-period, two-sequence, single dose with crossover. The dose, equivalent to 50 mg/m², was administered intravenously on the first day of each 28-day treatment period. Blood samples were collected at appropriate intervals for estimation of C_max, AUC_0-t, and AUC_0-∞ for free, encapsulated, and total doxorubicin, as well as partial AUC (AUC_0-48h, AUC_48h-last) for encapsulated doxorubicin.

Results: The 90% confidence intervals (CI) for the geometric mean ratio (GMR) of the primary endpoints for determination of bioequivalence namely, C_max, AUC_0-t, and AUC_0-∞ for free doxorubicin and encapsulated doxorubicin, and the 90% CIs for the secondary endpoints C_max, AUC_0-t, and AUC_0-∞ for total doxorubicin and partial exposure parameters AUC_0-48h and AUC_48h-last of encapsulated doxorubicin, were within the range confirming that the two formulations are bioequivalent. The incidence of treatment-emergent adverse events in the test and reference product was 95.7% (44/46) and 100% (42/42), respectively (p > 0.05).

Conclusion: The two formulations examined in the cohort of 48 Chinese patients with advanced breast cancer using measurements of free and encapsulated doxorubicin concentrations were bioequivalent. Both agents were well tolerated, and differences were not significant.

Objective: This study aimed to investigate the baseline neutrophil count as a risk factor for ganciclovir-induced neutropenia in greater detail.

Materials and methods: This retrospective observational study included patients who received ganciclovir at Kindai University Nara Hospital between April 2006 and June 2023. Exclusion criteria were as follows: patients under 18 years of age, those who received chemotherapy within 2 weeks prior to ganciclovir administration, those who underwent blood transfusions or received granulocyte colony-stimulating factor injections during the observation period, those treated for fewer than 2 days, patients with a baseline neutrophil count < 1,000 cells/mm³, and patients with missing data on any study variables. The primary endpoint was the occurrence of severe neutropenia, which was analyzed using Cox regression analysis and the Cochran-Armitage trend test.

Results: To the 345 patients who met the inclusion criteria, exclusion criteria were applied, and 158 were ultimately identified as eligible patients. Patients with baseline neutrophil counts < 1,500 cells/mm³ were at significantly higher risk of severe neutropenia compared to those with baseline counts ≥ 4,000 cells/mm³ (HR = 16.86, 95% CI = 1.64 - 173.50, p = 0.018). Additionally, the incidence of severe neutropenia tended to increase significantly as the baseline neutrophil count decreased (p < 0.001).

Conclusion: These findings underscore the importance of monitoring baseline neutrophil counts before initiating ganciclovir treatment, particularly in patients with conditions associated with low neutrophil levels, such as hematological disorders.

Background: Berberine, a traditional Chinese medicine, has demonstrated significant therapeutic influences in treating diabetes, obesity, and diarrhea, among other conditions. It has exhibited potential therapeutic benefits for various neurodegenerative diseases, namely, Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD).

Aims: This study aims to elucidate the mechanism behind berberine pharmacological action in treating AD.

Materials and methods: We search the articles published in PubMed and CNKI and summarize the mechanism of berberine in AD.

Results: In recent years, as research into the pharmacology of berberine has deepened, researchers have discovered its strong neuroprotective properties. The ability of berberine to enhance cognitive function is thought to result from inhibiting the spread of AD-related proteins, reducing oxidative stress and inflammation, increasing choline levels, and regulating autophagy.

Conclusion: This review explores the latest research on berberine in AD, suggesting that berberine and its analogs may offer a promising new approach to treating the condition.

Objective: Cabotegravir is approved for HIV treatment (with rilpivirine) and prevention. The established cabotegravir population pharmacokinetic (PPK) model included 1.2% Asian participants. We aimed to compare cabotegravir pharmacokinetics between Asian and non-Asian populations and across Asian countries.

Materials and methods: Cabotegravir concentrations were collected from Asian participants in phase 1 and 3 studies. The applicability of the PPK model to Asian populations was validated by predicting the observed concentrations not included in model-building. Cabotegravir post-hoc pharmacokinetic parameters (long-acting absorption rate constant, weight-normalized apparent clearances and volumes of distribution) and exposures (trough and peak concentrations) following monthly and every-2-month regimens were estimated by fitting the PPK model to observed data. Non-Asian participants from the previous PPK dataset (1,697 males; 564 females) were used as comparator. Cabotegravir exposures in Asian and non-Asian were compared via simulations.

Results: 2,034 cabotegravir concentrations were collected from 162 Asian males (assigned male at birth) in China (n = 47), Japan (n = 17), Korea (n = 25), Thailand (n = 53), and Vietnam (n = 20), and 35 concentrations from 2 Asian females (assigned female at birth) in Korea. Cabotegravir pharmacokinetic parameters were similar between Asian and non-Asian participants. Cabotegravir exposures in Asian populations largely overlapped with but tended to be higher than non-Asian populations, suggesting similar efficacy. Cabotegravir exposures in Asian and non-Asian populations remained below the safety threshold, suggesting similar safety profiles. Cabotegravir pharmacokinetic parameters and exposures were similar across Asian countries.

Conclusion: No dose adjustment is recommended for Asian populations with and without HIV. Cabotegravir pharmacokinetic data from any Asian country/region may guide pharmacokinetic evaluation and regulatory considerations across Asian regions.

Aims: To investigate prescription patterns in children and adolescents receiving treatment for primary hypertension.

Materials and methods: Cumulative prescriptions within the 12-month period before the index date were analyzed for a cohort of 7,482 children and adolescents using Kaplan-Meier curves, stratified according to age group. Associations between age, sex, co-diagnoses, and the likelihood to be treated were evaluated using multivariable Cox regression.

Results: The percentage of adolescents, children aged 6 years and above, and children aged up to 5 years receiving antihypertensive therapy was low (15.7% for adolescents, 12.8% for children aged 6 years and above, and 10.3% for children aged up to 5 years). The numbers receiving an angiotensin-converting enzyme (ACE) inhibitor, the most frequently prescribed drug class, were 65.4, 70.3, and 62.8%, and the numbers receiving a β-adrenergic receptor blocker, the second most commonly prescribed drug class were 19.1, 16.7, and 14.0%, respectively. Using multivariable analysis, co-diagnoses for type 1 diabetes mellitus (HR: 2.47; 95% CI: 1.72 - 3.55) and epilepsy (HR: 2.46; 95% CI: 1.74 - 3.47) were significantly correlated with an increased likelihood to receive antihypertensive therapy.

Conclusion: The low number of children and adolescents with primary hypertension prescribed antihypertensive therapy is not in accord with current treatment guidelines. The reasons for this discrepancy and the effect it has on long-term cardiovascular outcomes are of considerable concern and need to be investigated.

Purpose: To evaluate skin toxicity associated with immune checkpoint inhibitors (ICIs) using data mining and the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

Materials and methods: Data on skin toxicity associated with the use of ICIs were retrieved for the period January 2011 to September 2023. Analysis was done using various methods, including reporting odds ratio (ROR) estimates, proportional reporting ratios (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker estimates (MGPS). Mortality and hospitalization data were also assessed.

Results: A total of 8,129 skin toxicity reports concerning "ICIs" as the "primary suspected cause" were documented, accounting for 18.89% of all reported adverse events. Anti-PD-1 agents showed the highest incidence of skin toxicity, whereas anti-CTLA-4 monotherapy was associated with the most significant changes in ROR, PRR, empirical Bayesian geometric mean (EBGM), and information component (IC) values. The median onset of toxicity was 17 days after commencement of ICI treatment, consistent across sexes, age groups, and ICI types. The highest mortality rate occurred with anti-PD-1 treatment (11.37%), and there was a significant difference in mortality rates between different ICI treatments (monotherapy vs. combination therapy) (p = 0.03).

Conclusion: Differences are present between ICI regimens in the pattern of skin toxicity with anti-PD-1 therapies exhibiting the highest incidence of skin toxicity and mortality rates, while anti-CTLA-4 therapies showed the most marked signals.