Recipient hypertonic saline infusion prevents cardiac allograft dysfunction

Objective

Hypertonic saline (HTS) has potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and left ventricular (LV) dysfunction following transplantation.

Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen

Introduction: Tamoxifen dominates the anti-estrogenic therapy in the early and metastatic breast cancer setting. Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30–100 times more potent metabolite, endoxifen. Recently, a phase I study in which endoxifen as an orally z-endoxifen hydrochloride has been successfully evaluated.

Areas covered: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, since CYP2D6 genotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functional CYP2D6 genotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.

Expert opinion: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available.     

UPLC-MS/MS测定73例患者血中头孢哌酮与舒巴坦的浓度

目的：建立液相色谱-串联质谱法（UPLC-MS/MS）同时测定人血浆中头孢哌酮与舒巴坦的浓度，分析头孢哌酮/舒巴坦血药浓度监测结果，为临床合理用药提供参考。方法：以氯唑沙宗为内标，采用Waters BEHC₁₈柱（2.1 mm×100 mm，1.7 μm）进行分离，通过串联质谱仪，负离子检测模式下，以多反应监测（MRM）方式进行定量测定。对某院2018年以不同给药方案进行治疗的73例住院患者测定的头孢哌酮/舒巴坦血药浓度结果进行分析。结果：头孢哌酮与舒巴坦在测定条件下1~200 mg·L^-1范围内线性关系良好，两者日内精密度RSD均<10%，基质效应分别为（72.77±0.99）%与（75.72±0.11）%，提取回收率均>90%。73例患者共监测血药浓度96次，其中不同给药方案2 g，q8 h（43例次）；2 g，q12 h（26例次）；2 g，q6 h（27例次），各组头孢哌酮血药浓度的中位数分别为34.12 mg·L^-1（4.12~177.79 mg·L^-1）、31.23 mg·L^-1（1.89~251.8 mg·L^-1）、59.96 mg·L^-1（1.77~140.58 mg·L^-1），舒巴坦血药浓度的中位数分别为6.3 mg·L^-1（0.61~136.01 mg·L^-1）、28.83 mg·L^-1（0.5~133.69 mg·L^-1）、11.17 mg·L^-1（0.73~143.53 mg·L^-1）。Mann-Whitney U检验显示，头孢哌酮血药浓度结果无统计学差异（P>0.05），舒巴坦有统计学差异（P<0.05）。结论：本检测方法操作简便、快速、重复性好，可满足临床头孢哌酮与舒巴坦浓度的检测；头孢哌酮/舒巴坦在不同给药方案下血药浓度结果与个体差异相关，有必要开展血药浓度监测并依据结果适时调整用药方案，提高治疗效果减少耐药率的发生。     

2015—2017年解放军总医院抗震颤麻痹药物的使用情况分析

目的 了解解放军总医院抗震颤麻痹药物的应用情况与用药趋势。方法 采用世界卫生组织（WHO）推荐的以限定日剂量（DDD）为指标的分析方法，对2015-2017年解放军总医院抗震颤麻痹药物的销售金额、用药频度（DDDs）、日均费用（DDC）及排序比（B/A）等进行统计分析。结果 普拉克索、多巴丝肼和恩他卡朋的用药金额始终处于前3位，普拉克索的用药金额逐渐上升，卡比多巴/左旋多巴的用药金额逐渐下降；DDDs排序列前2位的是多巴丝肼和司来吉兰，多巴丝肼的DDDs逐年上升，一直处于第1位；2015-2016年各种抗震颤麻痹药物的DDC较为稳定，2016-2017年各种抗震颤麻痹药物的DDC开始略有下降；除普拉克索和恩他卡朋的B/A始终小于1.00，其他抗震颤麻痹药物的B/A均在1.00以上波动。结论 解放军总医院抗震颤麻痹药物的使用较为合理，其中多巴丝肼、普拉克索和司来吉兰具有很好的市场前景。     

How Do Students Source and Supply Drugs? Characteristics of the University Illegal Drug Trade

Background: It is widely known that a proportion of university students use drugs. However, much less is known about how they source and supply their drugs. Objectives: In this article, we investigate student drug trading activity, including how they obtained their drugs, whether they sold drugs, and the extent to which their drug trading might be described as a form of “social supply”. Methods: A survey was conducted of all students across seven of the nine universities of Wales. In total, 7855 students submitted a questionnaire and 1877 of these reported drug use in the current academic year. All students who reported using one or more illegal drugs in the current academic year were asked how they obtained their drugs, how they funded their drug use, whether they had sold, traded or given away illegal drugs, along with their motives for drug trading. Results: The results showed that about half of users obtained drugs solely from friends and associates and one-fifth obtained them solely from external dealers. One-quarter used friends and associates as well as external markets. In many cases, supplying drugs amounted to sharing them or giving them away. However, over one-third of students said that they had sold drugs. Conclusions: Overall, the methods of sourcing and supplying drug among university students shares features of both “social supply” and “traditional” drug markets. We conclude that the student drug market investigated is best described as a “hybrid” combination of both.     

Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CL_R) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CL_R (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CL_R of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates.     

Research on medication use in the neonatal intensive care unit

Introduction: Research on medication use aims at assessing how much of current pharmacotherapy is rational. In neonates, this is hampered by extensive off-label drug use and limited knowledge.

Areas covered: We report on medication use research and have conducted a systematic review of observational studies on medication use to provide an updated overview on characteristics, objectives, methods, and patterns in hospitalized neonates. Moreover, a review on aspects of medication use for opioids, anti-epileptics, gastric acid-related disorders and respiratory stimulants with emphasis on trends and impact of interventions is presented, illustrating how research on medication use can contribute to improved neonatal pharmacotherapy and more focused research. Medication use reports describe patterns and provide signals on irrational use, benchmarking, or can guide research priorities. Moreover, this may generate information on how neonatal health topics and their pharmacotherapy are handled over time or across regions.

Expert opinion: Research on medicine utilization is relevant, since it will inform us on aspects like trends, variability, or about the impact and pattern of implementation of guidelines in neonates. Further progress necessitates to merge datasets on medication use with clinical characteristics, and perinatal drug use remains an area in need of additional research.     

Eating sweets without the wrapper: perceptions of HIV and sexually transmitted infections among street youth in western Kenya

Street-connected youth in Kenya are a population potentially at risk of HIV transmission, yet little is known about their perceptions and experiences of sexually transmitted infections (STIs), despite their living in an HIV endemic region. We sought to elucidate the language and sociocultural factors rooted in street life that impact on street-connected young people’s knowledge of and perceptions about the prevention and transmission of STIs, and their diagnosis and treatment, using qualitative methods in western Kenya. We conducted a total of 25 in-depth interviews and 5 focus-group discussions with 65 participants aged 11–24 years in Eldoret, Kenya. Thematic analysis was conducted and data were coded according to themes and patterns emergent until saturation was reached. In general, street-connected young people knew of STIs and some of the common symptoms associated with these infections. However, there were many misconceptions regarding transmission and prevention. Gender inequities were prominent, as the majority of men described women as individuals who spread STIs due to unhygienic practices, urination and multiple partners. Due to misconceptions, gender inequity and lack of access to youth-friendly healthcare there is an urgent need for community-based organisations and healthcare facilities to introduce or augment their adolescent sexual and reproductive health programmes for vulnerable young people.