Journal of Clinical Pharmacy and Therapeutics最新文献

What Is Known? and Objective. Ceftriaxone has been widely used to treat bacterial meningitis in pediatric patients. Ceftriaxone dosing regimens of 80–120 mg/kg/day have been recommended for bacterial meningitis in pediatric patients, and the usual duration of therapy is 7–14 days. Although the target site for meningitis is cerebrospinal fluid (CSF), a CSF pharmacokinetic (PK) model in pediatric patients has not been reported. We aimed to develop a CSF PK model of ceftriaxone, using not only serum but also CSF concentration data, and to evaluate the appropriateness of dosing regimens for pediatric patients with bacterial meningitis. Methods. The population PK model was developed by simultaneously fitting serum and CSF data from pediatric patients described in nine published articles. Probabilities of attaining a pharmacodynamic target (100% T > MIC, 100% of time that drug concentrations above the minimum inhibitory concentration) in CSF were estimated for some dosing regimens. Results and Discussion. Twenty-four pediatric patients with meningitis were the subjects for PK modeling (0.52–13 years old, and 3.5–50 kg of body weight). Sixty-eight serum concentrations and 98 CSF samples were used to develop the CSF PK model. The CSF/serum concentration ratio at the same sampling time was 0.0628 ± 0.0689. Age was not a statistically significant covariate in the PK parameter. In the CSF PK model, 40–60 mg/kg q12 h achieved a target attainment probability >90% against causative bacteria for bacterial meningitis. However, 4-h infusion (rather than 0.5-h infusion) dosing regimens were required for efficacy against antimicrobial-resistant bacteria with high MICs. What Is New? and Conclusion. Ceftriaxone-dosing regimens with prolonged infusion times might be reasonably effective for treating antimicrobial-resistant pathogens in empiric therapy.

Background and Objective. Approximately 50% of acute ischemic stroke (AIS) patients who achieve complete recanalization after endovascular therapy (EVT) experience unfavorable outcomes that are potentially partially attributed to incomplete microvascular reperfusion, which can possibly be improved by antiplatelet treatment. This study aimed to evaluate the effect of periprocedural tirofiban on AIS patients who achieved complete recanalization with EVT. Methods. Anterior circulation large-vessel occlusion stroke patients who achieved complete recanalization after EVT were retrospectively analyzed. Patients were dichotomized into tirofiban and nontirofiban groups and compared. Propensity score matching (PSM) was used to balance baseline confounders. 3-month functional independence (modified Rankin scale: 0–2), any intracranial hemorrhage (ICH), symptomatic ICH (sICH), arterial reocclusion, in-hospital mortality, and 3-month mortality were evaluated. Results. This study included 303 patients with 118 and 185 in the nontirofiban and tirofiban groups, respectively. After PSM, 85 couples with balanced baseline characteristics were generated. 49 (57.6%) and 36 patients (42.4%) in the tirofiban and nontirofiban groups achieved functional independence at 3 months with a significant difference (risk ratio: 1.361, 95% confidence interval: 1.001–1.852, P = 0.046). However, there was no significant difference between the tirofiban and nontirofiban groups in terms of the other outcomes (all P > 0.05). Conclusions. In anterior circulation, large-vessel occlusion AIS patients who achieved complete recanalization with EVT, periprocedural tirofiban may improve the functional outcomes and does not appear to increase the rate of ICH and sICH.

Purpose. Hypertension (HTN) is one of the most common adverse drug reactions to tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor (VEGF), but little is known about its clinical risk factors. The aim of this study was to elucidate the association between baseline clinical characteristics and the occurrence of HTN in advanced gastric cancer (GC) patients prescribed apatinib, a commonly used VEGF-TKI in China, in a real-world setting. Patients and Methods. Fifty-five GC patients treated with apatinib from December 1st, 2016, to December 1st, 2020, were retrospectively included in electronic medical records. Adverse drug reactions were defined according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Univariate and multivariable logistic regression analyses were used to investigate potential clinical risk factors for apatinib-related HTN. Results. The incidence of apatinib-related HTN of all grades was 45.45%, and grade 3 HTN occurred in 16.36% of patients. The median maximal systolic blood pressure (SBP) during apatinib treatment was 153 mm·Hg, and the median time to event was 25 days. New-onset HTN occurred in 10/33 (30.30%) patients. Preexisting HTN (odds ratio [OR]: 4.155; 95% confidence interval [CI]: 1.252, 13.787; p = 0.020) was the key independent risk factor associated with apatinib-related HTN. Conclusion. The incidence of HTN was high in patients treated with apatinib, and preexisting HTN was an independent risk factor. It is important to provide thorough and close monitoring of patients during treatment with apatinib, especially for those with preexisting HTN. This trial is registered with ChiCTR1900024531.

Background/Purpose(s). We have extensively used HCQ at 200 mg three times a day (tid) to treat various infections such as Q fever and Whipple’s disease. Serum levels of between 1 μg/ml and 2 μg/ml serum level are recommended to achieve the safety and efficacy of these treatments. Our aim in this paper is to describe our experience regarding the pharmacokinetics and toxicity of HCQ in another infection caused by SARS-CoV-2. Methods. As recommended, we performed electrocardiograms before administering HCQ off-label. The HCQ concentration in the serum was monitored to ensure the effectiveness and safety of the treatment. We retrospectively analysed HCQ serum concentrations measured over time and toxicity data in patients with COVID-19 who were treated with HCQ at the IHU Marseille Infection. We did not treat patients with HCQ contraindications with this medication. Results. We measured HCQ concentrations in 1310 serum samples from 989 patients with COVID-19. The mean ± SD HCQ concentration increased in patients’ sera during treatment from day 1 (0.10 μg/ml ± 0.08) to day 11 (0.85 μg/ml ± 0.44), confirming that HCQ accumulates in the body during short-term therapy. However, the observed concentrations did not exceed the therapeutic range for other indications (0.80–1.20 μg/mL in Q fever patients treated for between 18 and 24 months). In patients treated with HCQ, major side effects included intestinal disorders (nausea, vomiting, and gastric pain) and QT prolongation. No conduction disorders (including torsades de pointes and ventricular arrhythmia), cardiomyopathy, retinopathy, or HCQ-related deaths were observed. Conclusions. In patients treated over a short time period with 200 mg tid of HCQ, therapeutic concentrations in serum were obtained in most patients without significant side effects or complications. Although patients must be carefully evaluated for HCQ contraindications, HCQ 200 mg tid for ten days can be considered an appropriate and safe dosage in patients with COVID-19.

Background. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage pain, including chronic pain conditions. However, their prolonged use is associated with significant risks, particularly gastrointestinal (GI) adverse events. This study aimed to evaluate the effectiveness and safety of a pharmacist-managed deprescribing program for NSAIDs in a Jordanian outpatient population. Methods. A convenience sample of 100 participants who had been using NSAIDs for pain management was recruited. Participants underwent a structured deprescribing intervention in collaboration with physicians. Various effectiveness and safety outcomes were assessed before and after deprescribing. Descriptive statistics and chi-square test were used for data analysis. Results. The majority of participants reported chronic pain conditions, with rheumatoid arthritis (24%) and osteoarthritis (22%) being the most prevalent. Ibuprofen (28%) and diclofenac (22%) were the most commonly used NSAIDs. The deprescribing program was associated with a significant reduction in heartburn, stomach ulcer, kidney problems and fluctuation in blood pressure readings (p < 0.05), and pain exacerbation. Notably, the reduction in pain exacerbation was evident (p = 0.003) in the 4-month follow-up. Conclusion. A pharmacist-managed NSAIDs deprescribing program demonstrated effectiveness in reducing the risk of GI adverse events and fluctuation in blood pressure readings without causing harm during a short-term follow-up. These findings support the feasibility of implementing such programs in outpatient settings. Further long-term investigations are necessary to confirm these results.

Berberine, an active compound extracted from the Chinese herb, was reported to have an antibacterial effect and an anti-inflammatory effect and promote osteogenic differentiation of human dental pulp stem cells. However, the underlying therapeutic mechanism of berberine in pulpitis is still unknown. Here, bioinformatics analysis was performed to investigate the potential mechanism of berberine against pulpitis. First, we identified the collective targets of berberine and pulpitis from several databases using a Venny online tool. The pattern of interaction between berberine and the targeted protein was visualized by molecular docking. Moreover, we performed GSEA, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to obtain potential pathways. Cell experiments were performed to validate the bioinformatics analysis results. Prostaglandin-endoperoxide synthase 2 (PTGS2) was identified as the crucial antipulpitis target of berberine via the CytoHubba plugin. Docking analysis indicated that berberine could fit in the binding pocket of the PTGS2 protein. Additionally, berberine exerted its therapeutic effects against pulpitis via multiple pathways. Overall, berberine possessed therapeutic effects against pulpitis through the inactivation of toll-like receptor and NOD-like receptor signaling pathways. The present research proposes a novel approach to explore the therapeutic mechanism of natural products.