Exposure–response analyses of blood pressure and heart rate changes for methylphenidate in healthy adults

The aim of the study was to evaluate the exposure–response (E–R) relationships of blood pressure (BP) and heart rate (HR) changes in healthy adults taking methylphenidate (MPH). Intensive time profiles of BP and HR from healthy adults in placebo and MPH treatment arms of seven clinical trials from the FDA internal database were utilized for this analysis. The analysis model contains a circadian component for placebo effect and an E–R component to describe drug effect. Internal validation was performed using goodness-of-fit plots and visual predictive check. A meta-database based on a systemic literature search was constructed and used for external validation of the developed models. We found that circadian models could quantify the time profiles of BP/HR in placebo arms. Linear models could describe the correlations between MPH concentrations, and BP/HR changes. The BP and HR changes were highly dependent on the shapes of MPH pharmacokinetic (PK) profiles without an apparent time delay. MPH has the greatest effect on HR, followed by systolic BP, and diastolic BP. Internal validation revealed that the developed models could adequately describe the circadian rhythms of HR and BP in placebo arms and the E–R relationships of MPH. External validation showed the models had good predictive capability of the literature data. In conclusion, the developed models adequately characterized the circadian rhythm and the MPH induced effects on BP and HR. The changes in BP and HR were highly correlated with MPH blood levels with no apparent delay. The time courses of BP and HR are similar to the MPH PK profiles. As a result, the immediate-release formulation may yield larger maximum BP and HR effect than the extended-release formulation under similar dose.     

注射用血栓通中三七元素迁移的规律

目的:分析注射用血栓通中三七从原料到成品全过程的元素迁移规律,以便更好地控制成品中元素杂质。方法:采用ICP-MS法全面分析三七药材、三七总皂苷(中间体)和注射用血栓通中21种元素的含量。结果:21种元素的标准曲线相关系数r均在0. 999以上,回收率在92. 71%～107. 07%之间,RSD均在5%以内。三七药材中铝、铁含量较高,铅、砷、汞、镉、铜符合中华人民共和国药典的相关规定,三七总皂苷(中间体)和注射用血栓通中多数元素均未检出或含量极低。结论:注射用血栓通的提取工艺可有效去除三七中大部分元素,重金属及有害元素也降到较低水平。     

Diagnosis and treatment of vertebral hemangiomas with neurologic deficit: a report of 29 cases and literature review

Background contextVertebral hemangiomas (VHs) are called benign tumors but are actually just vascular malformations. The diagnosis and treatment for aggressive VHs is still controversial, due to their rarity.PurposeTo evaluate the safety and efficiency of the present diagnostic methods and treatment choices.Study designA retrospective study of aggressive VHs with neurologic deficit.Patients sampleA total of 29 consecutive aggressive VH cases were diagnosed and treated in our department since 2001.Outcome measuresWe routinely took anteroposterior and lateral spinal roentgenograms, computed tomography, and magnetic resonance images.MethodsTrocar biopsy is indicated in suspected malignant cases. Radiotherapy was usually our first choice if the neurologic deficit was mild or developed slowly. Surgery was indicated if the neurologic deficit was severe or developed quickly or if the radiotherapy was not effective.ResultsThis series included 12 males and 17 females, and the mean age at diagnosis was 44.0 years (range, 21–72 years). Ten patients had radiculopathy, 1 had cauda equina syndrome, and 18 cases had myelopathy. Twenty-one cases had lesions in the thoracic spine, 5 in the lumbar, and 3 in the cervical region. Eleven cases had untypical image findings, including five cases with pathologic vertebral fracture. The neurologic compression came from only epidural soft tumor mass in 18 cases, whereas it came from both bony compression and soft lesion in the other 11 cases. Ten cases had radiotherapy alone, but two failed and had surgery later. Twenty-one cases had surgery. In the 12 cases having surgical decompression without vertebroplasty, the average estimated blood loss was 1900 mL, and it was 1093 mL for the eight cases having decompression with vertebroplasty. The average follow-up was 51.1 months (range, 24–133 months). There was no recurrence in those cases with radiotherapy, whereas three had local recurrence in those six cases treated by surgical decompression alone without radiotherapy.ConclusionsIn aggressive VHs, epidural soft-tissue compression was usually the main reason for neurologic deficit. In cases with rapid progressive and/or severe myelopathy, posterior decompression and stabilization could be combined with intraoperative vertebroplasty to reduce blood loss.