International journal of clinical pharmacology and therapeutics最新文献

Objective: To evaluate potential drug-drug interactions between polyethylene glycol loxenatide (PEX-168) and warfarin.

Materials and methods: This was an open-label, single-arm, two-treatment, sequential study. 16 healthy male subjects were administered warfarin (5 mg) alone on day 1 and received PEX-168 subcutaneously 200 µg once a week during days 14 - 42, with warfarin (5 mg) on day 44. Pharmacokinetics of R- and S-warfarin, as well as pharmacodynamics of warfarin, as measured by prothrombin time (PT) and international normalized ratio (INR), were assessed.

Results: The geometric mean ratios (GMRs) of area under the curve from time zero to the time of the last quantifiable concentration (AUC_0-t) for PEX-168 + warfarin vs. warfarin were 0.950 (90% CI: 0.898, 1.006) for R-warfarin and 0.989 (90% CI: 0.946, 1.033) for S-warfarin. The GMRs of maximum observed plasma concentration (C_max) values were 0.965 (90% CI: 0.893, 1.043) for R-warfarin and 0.983 (90% CI: 0.899, 1.075) for S-warfarin, both of which were contained in the interval 0.80 - 1.25. PEX-168 had no effect on the area under the effect-time curve from time 0 to 168 hours of INR and PT, as demonstrated by the GMRs of 0.987 (90% CI: 0.974, 1.000) and 0.990 (90% CI: 0.979, 1.002), respectively.

Conclusion: Concomitant administration of PEX-168 and single-dose warfarin was well tolerated. PEX-168 had no effect on the pharmacokinetics or pharmacodynamics of warfarin.

Objectives: To demonstrate adequate skin adhesion of a new once-daily rotigotine transdermal patch (ROT-TDS) compared to the originator product (reference) in patients with Parkinson's disease (PD).

Materials and methods: Pharmacokinetic bioequivalence (PK BE) was assessed with the 4 mg/24h patches in healthy adults in a single-/multiple-dose, crossover trial. The trial investigating skin adhesion in PD patients (stable dose ≥ 8 mg/day rotigotine) was performed with the 8 mg/24h patches as a multiple-dose, crossover trial (4 alternating once-daily patch applications). Skin status (seborrhea, sweating) was characterized at screening. Adhesion was assessed 5 minutes after application and 5 minutes before removal of each patch. Systemic safety and skin irritation/sensitization were monitored.

Results: ROT-TDS was bioequivalent to the reference product in the PK BE trial in 48 randomized healthy subjects. In the skin adhesion trial in 43 randomized PD patients, the cumulative mean percentage of adhesion (90% CI) at the end-of-dosing interval was 92.948% (90.156 - 95.740%) for ROT-TDS and 90.471% (87.574 - 93.367%) for the reference. For ROT-TDS, 80.23% of patches were ≥ 90% adhered at the end-of-dosing interval, while this was the case for 67.44% of the reference patches. Safety and skin tolerability of both products were comparable; the most frequent treatment-related adverse event was application-site pruritus for both treatments at comparable extent.

Conclusion: ROT-TDS - with shown BE to the originator reference product - displayed similar safety and local tolerability as the reference product in patients with PD. The results show a trend to improved skin adhesion of the new patch compared to the reference in the target population.

Objectives: We aimed to study sarcopenia for its significance in predicting the effect of hepatic artery intervention (HAI) plus lenvatinib on hepatitis B-related hepatocellular carcinoma (HCC) complicated with diabetes mellitus (DM).

Materials and methods: Hepatitis B-related HCC patients complicated with DM (n = 102) visiting during January 2021 and December 2023 were retrospectively selected. Computed tomography was performed to detect the third lumbar vertebra for its muscle cross-sectional area. A non-sarcopenia group (59 cases) plus a sarcopenia group (43 cases, men with a skeletal muscle index ≤ 40.8 cm²/m² and women with a skeletal muscle index ≤ 34.9 cm²/m²) were established according to different skeletal muscle indexes.

Results: Significant decline in body mass index (BMI) and albumin (ALB) level was observed in the sarcopenia group compared to the non-sarcopenia group (p < 0.05). The sarcopenia group, compared with the non-sarcopenia group, exhibited a significantly reduced objective response rate (53.49 vs. 74.58%) (p < 0.05), while no significant intergroup difference was discovered in the disease control rate (95.35 vs. 91.53%) (p < 0.05). Low BMI, alpha fetoprotein (AFP), low ALB, and pre-chemotherapy sarcopenia all influenced the overall clinical efficacy, as independent influencing factors (p < 0.05).

Conclusion: Sarcopenia may attenuate the efficacy of HAI plus lenvatinib on hepatitis B-related HCC with DM, and BMI, AFP and ALB are factors affecting the therapeutic effect.

Background: Patients discharged from intensive care units (ICUs) are at higher risk for medication discrepancies, which can harm patients, increase healthcare costs, and lead to readmission. This study aimed to describe the frequency and types of medication discrepancies among ICU patients upon discharge and identify the factors associated with medication discrepancies.

Materials and methods: This retrospective cohort study included patients ≥ 18 years old, admitted to medical or surgical ICUs, and discharged on one or more medications. This study was done at a tertiary university hospital in Riyadh, Saudi Arabia. Data were collected through chart review over a 3-month period in 2018. Medication discrepancy was defined as any difference identified between the documented home medication list and the medication list on ICU discharge without any clearly documented justification. χ², Fisher exact test, and logistic regression were used to analyze the data.

Results: Out of 204 screened patients, 121 were included. The mean age was 51 ± 15.7 years, 57 (47.1%) were female, and 91 (75.2%) were admitted to the surgical ICU. The median ICU length of stay was 3 (2 - 7) days. In total, 216 medication discrepancies were identified; only 23 (19%) patients were discharged without any medication discrepancies. The mean medication discrepancies identified per patient were 2 ± 1. The most common type of medication discrepancies identified were no indication of therapy (43.8%), drug omissions (33.7%), and discrepancies in the duration of therapy (11.2%). Mechanically ventilated patients were less likely to have medication discrepancies upon discharge (OR = 0.24, 95% CI = (0.07 - 0.90)).

Conclusion: This study demonstrated many medication discrepancies among patients discharged from ICUs at KSUMC University Hospital in Riyadh, Saudi Arabia. The lack of a systematic approach to medication reconciliation might contribute to the increased number of medication discrepancies in comparison to multiple studies in different countries exploring the medication discrepancies among ICU patients. Establishing a process that includes pharmacist-driven medication reconciliation is needed.

Background: Serratia marcescens has recently been categorized as low-risk for AmpC β-lactamase inducible production, but research on outcomes in Serratia bacteremia by antibiotic choice is limited.

Objectives: This study examined the clinical characteristics and outcomes of patients with ceftriaxone-susceptible Serratia bacteremia who received AmpC-directed β-lactam therapy vs. narrower spectrum therapies.

Materials and methods: Records of hospitalized adults with at least one positive blood culture for Serratia, over an 8-year period, across seven hospitals in an integrated health care system, were reviewed.

Results: Of the 73 identified patients, 17 (23.3%) received carbapenem-based therapy. More than half of cases were community-acquired, with urological and intravenous drug use being the most common sources. While there was a trend toward lower mortality in carbapenem-treated patients (14.8 vs. 0%; p = 0.10), this was not statistically significant. The composite outcome of clinical failure was also not significant. However, compared to non-carbapenem-treated patients, carbapenem-treated patients had longer treatment duration (13 vs. 15 days; p = 0.02), prolonged hospital stays (5 vs. 11 days; p < 0.001), and higher infection-related readmission rates (17.6 vs. 3.6%; p = 0.04). A subset analysis of the 56 non-carbapenem treated patients found no significant difference in 30-day mortality or clinical failure between cefepime and non-cefepime-containing subgroups.

Conclusion: Our study found that cefepime- or carbapenem-based therapy may have limited clinical relevance in the treatment of Serratia bacteremia when the strains are initially susceptible to ceftriaxone, highlighting the importance of antibiotic stewardship to prevent emergence of multidrug resistant organisms.

Objective: The purpose of this study is to evaluate the pharmacokinetics (PK) parameters of an ezetimibe 10 mg (test drug) and assess its bioequivalence to the branded reference product in healthy Chinese subjects under fasting and fed conditions.

Materials and methods: A single-center, randomized, open-label, four-period, two-sequence, full replicate crossover study was conducted in 88 healthy Chinese subjects under fasting or fed conditions. Subjects received a single oral dose of 10 mg ezetimibe tablet as test or reference formulation. There was a minimum 14-day washout period between each dose. Blood samples were collected at prescribed time intervals, the plasma concentration of free ezetimibe and total ezetimibe (ezetimibe + ezetimibe glucuronide) was determined by a validated ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Pharmacokinetik and bioavailability parameters were estimated via non-compartmental methods. Adverse events were also recorded.

Results: 40 and 48 eligible healthy subjects were enrolled in the fasted and fed study. Under fasting state, total ezetimibe with 90% confidence intervals (CIs) of C_max, AUC_0-t, and AUC_0-∞ were 87.17% (81.99 - 92.66%), 95.98% (92.38-99.72%), and 96.04% (91.37 - 100.95%), respectively. Under fed state, total ezetimibe with 90% confidence intervals (CIs) of C_max, AUC_0-t, and AUC_0-∞ were 98.71% (90.11 - 108.13%), 98.32% (94.71 - 102.06%), and 97.90% (92.68 - 103.42%), respectively. The 90% CIs of the ratio of geometric means (GMRs) of C_max, AUC_0-t, AUC_0-∞ of the test and reference formulation in both fasting and fed conditions fell within the conventional bioequivalence criteria of 0.80 - 1.25. No severe adverse events were observed.

Conclusion: The test and reference 10-mg ezetimibe tablets were bioequivalent under fasting and fed conditions in Chinese subjects. Both preparations showed good safety and tolerability.

Currently, there are no effective treatments for amyotrophic lateral sclerosis (ALS), a chronic progressive neurodegenerative disease. Although the etiology of ALS is unknown, it is thought that factors such as diet, the environment, and lifestyle habits play a role. The pathogenesis of ALS includes alterations in glutamate neurotransmission, oxidative stress, mitochondrial dysfunction. Drugs such as riluzole, edaravone, dextromethorphan/quinidine combinations, and the administration of tofersen by injection are approved treatment options for ALS although a number of other agents are being examined in clinical trials. Despite these developments, the availability of effective treatment options is limited. This review summarizes the etiology and pathogenesis of ALS and describes treatments in detail as an integrative medicine approach and including traditional Chinese medicine together with the importance of the timing for interventions, precautions necessary for noninvasive ventilator and gastrostomy surgery, and precautions for dealing with respiratory issues with the overall aim of providing state-of-the-art clinical recommendations for the care and therapy of ALS patients.

Objective: This study aims to investigate the clinical effectiveness and underlying pharmacological processes of a patented formulation derived from Chinese herbal medicine (CHM), named Qu's formula 7 (QUF7), in addressing polycystic ovary syndrome (PCOS).

Materials and methods: A retrospective analysis of clinical data was performed involving 225 patients diagnosed with PCOS. We categorized the subjects into two distinct groups: one receiving combined oral contraceptives (COCs) and the other undergoing QUF7 treatment. After treatment, the menstrual cycles and sex hormone levels of the two groups were evaluated. Moreover, an integrative pharmacology approach was utilized to explore the principal components, cardinal targets, and potential mechanisms associated with the QUF7 prescription in the treatment of PCOS.

Results: After treatment, patients in the QUF7 group exhibited a significant alteration in their menstrual periods and a pronounced decrease in blood luteinizing hormone (LH) levels compared to the COCs group (p < 0.05). The analysis of network pharmacology revealed a total of 332 intersecting targets associated with QUF7 and PCOS, and findings from molecular docking analyses indicated that 6-hydroxynaringenin has a robust affinity for estrogen receptor 1 (ESR1). The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis evaluation indicated that the advanced glycation end product (AGE)-AGE receptor (RAGE) and phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling pathways are the most probable underlying mechanisms.

Conclusion: QUF7 modulates endocrine levels and improves ovulation in PCOS patients and possibly exerts multi-targeted effects by mediating the signaling pathways of AGE-RAGE and PI3K-AKT.

Objective: Previous findings on predictors of vancomycin-induced acute kidney injury (AKI) are inconsistent. We aimed to identify the predictors of vancomycin-induced AKI using the Observational Medical Outcome Partnership Common Data Model.

Materials and methods: We analyzed data from patients treated with vancomycin between January 1, 2012, and May 31, 2022, who were positive for Staphylococcus aureus and had undergone oxacillin susceptibility tests. After excluding patients without data for vancomycin or baseline serum creatinine levels, 116 patients were included in the final dataset. Data up to the third measured vancomycin concentration were collected for each patient. Logistic regression models were used to estimate the odds ratio and 95% confidence interval for each variable associated with vancomycin-induced AKI.

Results: High baseline serum creatinine levels, intensive care unit admission, and concurrent renal disorders were significantly associated with vancomycin-induced AKI. Although high trough levels or area under the curve values were not significantly associated with vancomycin-induced AKI, both were significantly higher in patients with AKI than in those without AKI at the second vancomycin concentration measurement. The proportion with trough levels > 20 mg/L was higher in patients with AKI than in those without AKI at the third measurement.

Conclusion: Our findings revealed that underlying renal disease and intensive care unit admission are more significantly associated with vancomycin-induced AKI than vancomycin pharmacokinetic parameters or dosage, likely due to vancomycin concentration-based dosage adjustment in clinical settings. Our findings may help develop strategies for reducing the incidence of vancomycin-induced AKI; however, further prospective studies are essential.