长效二氢奎尼丁治疗40例心房纤颤患者的疗效与血药浓度的关系

目的:观察长效二氢奎尼丁治疗心房纤颤的疗效与血药浓度的关系.方法:10例心房纤颤病人一次po长效二氢奎尼丁,以TDx测定血药浓度.结果:T_(1/2(Ka))=(2.22±1.25)h,T_(1/2)=(8.22±4.25)h,T_(max)=(6.99±3.03)h,C_(max)=(0.6±0.41)μg/ml,AUC=(9.99±5.96)μg/(h·ml).结论:长效二氢奎尼丁治疗房颤时有效血药浓度为0.82～1.20μg/ml.     

血浆脑钠肽水平变化与心房颤动关系探讨

目的探讨血浆脑钠肽(BNP)水平与心房颤动(AF)的关系。方法选取72例患者,其中特发性AF34例,器质性心脏病AF38例,另选24名健康人组成对照组,采取放射免疫法测定各组BNP水平。结果AF组血浆BNP水平均比健康对照组有升高(P<0.05),随着AF分类级别的升高,血浆BNP水平明显增加(P<0.05),并且AF组转复为窦性心律后血浆BNP水平明显下降(P<0.05)。结论AF患者血浆BNP水平在不同类别的AF中有所不同。     

房颤患者hs-CRP及同型半胱氨酸与左房内径的关系

目的探讨房颤患者hs-CRP及同型半胱氨酸与左房内径的关系。方法选择房颤患者93例为房颤组,根据患者病情分为阵发性房颤亚组、持续性房颤亚组和永久性房颤亚组。选择同期在医院体检的健康体检者50例为对照组。比较各组hs-CRP、Hcy、左房前后径、左心室射血分数差异,分析hs-CRP、Hcy与左房前后径的相关性。结果对照组hsCRP、Hcy、左房前后径均显著低于房颤组[（2.2±0.7）mg/L vs（4.0±1.1）mg/L;（18.0±2.1）μmol/L vs（21.7±3.7）μmol/L;（38.8±2.7）mm vs（45.2±6.8）mm,P〈0.01];永久性房颤组水平最高,其次为持续性房颤组,均显著高于对照组（P〈0.01或P〈0.05）。hs-CRP、Hcy与左房内径呈显著正相关（r=0.943、0.870,P均〈0.01）。结论房颤患者hs-CRP、同型半胱氨酸水平显著升高,并且与左房内径呈显著正相关,提示炎症反应和氧化应激参与了房颤的发生和发展,并且与心房重构有关。     

地高辛血药浓度与临床疗效关系

目的:研究地高辛浓度与临床疗效之间的关系.方法:将353例口服地高辛的充血性心衰患者分成3组:有效组、无效组及中毒组.应用放射免疫法(RIA)对其稳态血药浓度进行测定同时观察疗效.结果;平均血药浓度有效组为(1.07±0.50)ng/ml,无效组为(0.97±0.54)ng/ml,中毒组为(2.74±1.35)ng/ml.有效组与中毒组之间血药浓度有显著性差异(P<0.001).有效组与中毒组之间单位剂量(mg·kg~(-1)·d~(-1))有显著性差异(P<0.01).有效组单位剂量为(0.004 0±0.001 2)mg·kg~(-1)·d~(-1),中毒组为(0.004 7±0.001 9)mg·kg~(-1)·d~(-1).结论:地高辛血药浓度的监测可以指导临床医生合理用药、提高疗效、避免或减少不良反应.     

同等剂量喹硫平治疗精神分裂症的血药浓度与临床疗效的关系

目的研究喹硫平同等剂量治疗精神分裂症时的稳态血药浓度与临床疗效间的关系。方法以固定剂量喹硫平(600 mg/d)治疗148例精神分裂症患者,疗效和不良反应采用简明精神病评定量表(BPRS)和副反应量表(TESS)进行评定,同时测定治疗第2、4、8周的稳态血清药物浓度。结果精神分裂症患者的BPRS减分率与血药浓度之间差异有显著性(P<0.05),血药浓度与不良反应(TESS分值)之间差异无显著性(P>0.05)。结论喹硫平的血药浓度检测有助于确定药物有效浓度及毒性浓度之间的范围,做到用药个体化,指导临床合理用药。     

The relationship between statin use and atrial fibrillation*

ABSTRACT

Objective: To investigate the relationship between statin therapy and the development of new-onset, recurrent, and postoperative atrial fibrillation (AF).

Research design and methods: A systematic literature search was conducted through September 2006. Included studies were either randomized, controlled trials or observational studies with adjusted analyses using multivariate regression or covariate matching, compared patients receiving or not receiving a statin, and reported data on the incidence of AF. Weighted averages were reported as odds ratios with 95% confidence intervals (CIs) using a random-effects model.

Main outcome measures: The primary outcome measured was a combined endpoint of any AF type. Secondary outcomes included new-onset, recurrent, and postoperative AF.

Results: Fourteen trials reporting the results of 15 unique analyses (n = 7402) were included. There was a 20% incidence rate for any AF with varying rates depending on AF type (new-onset [11%], recurrent [56%], recurrent after cardioversion [54%], postoperative [22%]). The use of a statin reduced the odds of developing any AF by 45% (odds ratio [OR] 0.55; 95% CI 0.43–0.70); Q statistic p = 0.001). Statins reduced the odds of developing new-onset AF by 32% (OR 0.68; 95% CI 0.51–0.90), recurrent AF by 57% (OR 0.43; 95% CI 0.24–0.79), recurrent AF after cardioversion by 42% (OR 0.58; 95% CI 0.32–1.05) and postoperative AF by 58% (OR 0.42; 95% CI 0.27–0.65).

Limitations: We considered studies that were observ­ational in nature or only available in abstract form. Publication bias could not be ruled out.

Conclusions: Statin therapy was associated with a reduced odds of developing AF, thus providing evidence of the benefit of statins beyond the lipid-lowering activity.     

高效液相色谱法测定静注吡洛地尔兔血药浓度及药物动力学参数

本文应用反相高效液相色谱法测定兔静注吡洛地尔（１５ｍｇ／ｋｇ）血药浓度，样品用正庚烷提取。流动相以１０％三乙胺：甲醇液（甲醇：水＝９：１）＝５：９５。紫外检测波长为２５４ｎｍ，回收率８１．４％，日内和日间的ＲＳＤ值为２．４％、３．５％。最低检测血浓为２０ｎｇ／ｍｌ。用３Ｐ８７程序拟合为二室模型。α＝３．０８ｈ－１，β＝０．１８ｈ－１，Ｔ１／２＝４．０７ｈ，Ｋ１０＝０．９１ｈ－１，Ｋ１０＝０．６１ｈ－１，Ｖｃ＝１１．４５ＡＬ／ｋｇ，ＣＬ＝６．７３Ｌ／（ｋｇ·ｈ），ＡＵＣ＝２．２１（μｇ·ｈ）／Ｌ。     

The relationship between mood state and plasma methadone concentration in maintenance patients

Although methadone maintenance is designed to stabilize opioid-dependent patients, some experience significant withdrawal in the latter part of the 24-hour interdosing interval. This study was designed to determine the mood changes that maybe associated with such withdrawal. Eighteen methadone patients, nine of whom experienced significant withdrawal, were tested over a single interdosing interval. During this time, 13 blood samples were collected to measure plasma racemic methadone concentrations, and the Profile of Mood States (POMS) was administered on 11 of these occasions. The POMS was also administered on 11 occasions over 24 hours to 10 drug-free healthy controls. In comparison with controls, methadone patients showed increased anger, depression, tension, confusion, and fatigue, as well as decreased vigor. For all scales, maximal differences from controls occurred at times of trough methadone concentration and minimal differences around the time of peak concentration. Changes in mood over the interdosing interval were more exaggerated in the nine patients who experienced significant withdrawal compared with those who did not. The composite Total Mood Disturbance (TMD) scores were calculated for each subject at each time point. The sigmoid Emax model was used to relate plasma concentrations to these data and to calculate the slope factor (N). This model could be fitted for 14 of the 18 patients with a mean +/- SEM slope factor of 2.2 +/- 0.5. TMD score was also shown to be inversely related to the rate of decline in methadone concentration from peak to trough. These results show that significant mood changes occur in response to changes in methadone concentration, and these are more pronounced in those who experience withdrawal. The concentration-effect relationships suggest that relatively small changes in plasma concentration will result in significant mood change. Differences in the degree of mood change between those who do and do not experience significant withdrawal may be explained by variation in the rate of decline in plasma concentration from peak to trough.     

奎硫平及其代谢产物血药浓度与疗效、副作用的相关性

目的 探讨奎硫平及其代谢产物血药浓度与疗效、副作用的相关性。方法 对15例精神分裂症患者给予富马酸奎硫平治疗,剂量为400mg·d-1,疗程为3周。采用阳性症状量表(SAPS)、阴性症状量表(SANS)、简明精神病量表(BPRS)和不良反应量表(TESS)于治疗前和治疗1、2、3周末分别评定疗效和副作用。治疗第8 d晨服药前和服药后1.5 h分别采静脉血2 mL,高效液相色谱-质谱联用测定奎硫平及其代谢产物血药浓度。结果治疗结束时,SAPS、SANS和BPRS评分较治疗前均显著降低;BPRS减分率及SAPS减分率仅与奎硫平的稳态谷浓度均呈正相关;SANS减分率与峰、谷浓度均不相关。不良反应主要为一过性头昏和心动过速;TESS中的抗α1肾上腺素因子分值与奎硫平稳态峰浓度正相关,TESS总分值及其他因子分值与奎硫平及其代谢产物血药浓度不相关。结论 奎硫平治疗精神分裂症疗效好、起效快、耐受性好;监测奎硫平血药浓度对优化奎硫平临床疗效和预防药物不良反应具有重要意义。     

ACE基因多态性与缬沙坦治疗房颤合并心功能不全患者疗效的相关性

目的探讨血管紧张素转化酶(ACE)基因多态性与缬沙坦治疗房颤合并心功能不全患者疗效的关系。方法选取2017年1-12月在我院接受缬沙坦治疗的持续性房颤合并心功能不全患者,共82例。收集年龄、性别、体重及入院时心功能指标,并检测分析ACE I/D、G2350A基因多态性,比较不同位点基因分型与缬沙坦治疗效果的关系。结果随着治疗后随访时间的延长,ACE I/D基因中DD、II基因型患者窦性心律维持率明显下降(P<0.05)。与ACE ID型、DD型比较,II型治疗后9、12个月窦性心律维持率均显著升高(P<0.05);ACE G2350A基因中GG、GA基因型患者窦性心律维持率明显下降(P<0.05)。与ACE GG型、GA型比较,AA型治疗后12个月窦性心律维持率均显著升高(P<0.05)。与复发患者比较,未复发患者心功能、LVEF、BNP以及ACE G2350A基因中AA基因型比例和I/D基因中II基因比例明显升高,SBP明显下降(P<0.05)。BNP是房颤复发的独立危险因素,心功能分级(Ⅱ级)、I/D位点基因分型(II)、G2350A位点基因分型(AA)则是保护因素(P<0.05)。结论 ACE I/D基因和G2350A基因多态性与缬沙坦治疗房颤合并心功能不全患者疗效密切相关,且2个位点的基因多态性之间可能存在一定协同作用,可为个性化临床用药方案的确定提供新的科学依据。     

肾移植术后环孢素A血药浓度监测与临床疗效关系

目的:研究肾移植(RT)术后环孢素A(CsA)浓度与临床疗效之间的关系。方法:将RT患者分成3组:正常组、中毒组、排异组。应用荧光偏振免疫(FPIA)法,对921例次RT术后患者进行常规CsA血药浓度监测,同时观察疗效。结果:平均血浓度正常组为256.10±47.52ng/ml;排异组为142.25±44.71ng/ml;中毒组为432.96±107.99ng/ml。正常组分别与中毒组、排异组之间血药浓度的显著性差异(P<0.001)。结论:CsA血药浓度监测可以指导临床合理用药,避免或减少不良反应。     

帕利哌酮缓释片治疗精神分裂症患者的血药浓度与临床疗效

目的 探讨帕利哌酮缓释片治疗精神分裂症患者的血药浓度与临床疗效的相关性。方法 选择2014年9月—2017年8月在新乡医学院第二附属医院诊治的101例精神分裂症患者,给予帕利哌酮缓释片治疗,在治疗第2、4、8周进行帕利哌酮血药浓度检测,同时进行临床疗效、不良反应的判定与记录。结果 101例患者的帕利哌酮缓释片平均口服剂量为（6.30±0.98）mg/d,平均血药浓度为（31.90±14.29）ng/mL,治疗第2、4、8周的服药剂量与血药浓度对比无显著差异。治疗第2、4、8周的有效率分别为82.2%、92.1%、98.0%,对比差异显著（P<0.05）。治疗第2、4、8周的不良反应发生率分别为8.9%、9.9%、10.9%,对比无显著差异。Spearman非参数相关分析显示帕利哌酮的血药浓度与临床疗效有效率间无显著相关性（r=0.154）;治疗第8周,发生不良反应的患者血药浓度明显高于未发生不良反应（P<0.05）。结论 帕利哌酮缓释片治疗精神分裂症有很好的治疗效果,随着帕利哌酮缓释血药浓度的增加,临床疗效无显著增加,但是可增加不良反应发生率,需要合理调整用药剂量。     

心房颤动患者血浆D-二聚体与纤维蛋白原变化

目的观察慢性心房颤动(房颤)患者血浆D-二聚体和纤维蛋白原水平的变化,并探讨其意义。方法测量48例房颤患者(其中风心病28例,冠心病20例)和30例正常人血浆D-二聚体(D-dimer)和纤维蛋白原(Fg)。结果房颤患者与正常人相比,血浆D-dimer浓度极显著升高(P<0.01),纤维蛋白原水平也显著升高(P<0.01)。风心病患者与冠心病患者之间D-dimer,Fg差异均无显著性意义(P>0.05)。结论房颤患者血浆D-dimer和Fg水平升高,可能与其高发血栓栓塞并发症有关。     

The relationship between the QT interval and plasma amiodarone concentration in patients on long-term therapy

Summary We have studied 27 patients on long-term treatment (6–60 months) with amiodarone (dose range 350 mg per week to 2800 mg per week) to ascertain whether the corrected QT interval could predict plasma amiodarone or plasma desethylamiodarone concentration. The patients were assessed on three or four occasions one month apart.There were positive correlations for % QTc and plasma amiodarone and % QTc and plasma desethylamiodarone.There was approximately a four-fold variation for % QTc and plasma amiodarone. This variation was not accounted for by between-occasion variation in the QTc interval, as the coefficient of variation was 2.1%. In six of the patients % QTc either decreased or did not change.% QTc is not a reliable predictor of plasma amiodarone concentration in the individual patient over time.     

The relationship between plasma concentration of valproic acid and its anticonvulsant and behavioural effects in the rat

The relationship between the plasma concentration of valproic acid (VPA) and anticonvulsant or neurotoxic effects was studied in the rat. Anticonvulsant activity was assessed against; (1) maximal seizures induced either by electroshock or by intravenous injection of pentylenetetrazol; and (2) kindled amygdaloid epilepsy. Drug-induced neurotoxicity was determined by the rotarod test and by observation of behaviour. In the maximal seizure tests, tonic hindlimb extension was always abolished at plasma valproic acid concentrations of 225 microgram ml-1 and above. Tonic forelimb extension was not consistently blocked until the plasma drug concentration exceeded 530 microgram ml-1. In fully-kindled rats, plasma valproic acid concentrations of 300 microgram ml-1 and above markedly reduced the duration of amygdala afterdischarge activity and the intensity of behavioural seizures produced by amygdala stimulation. Analysis of the data from individual kindled rats revealed that there was a significant correlation between the estimated plasma concentration of valproic acid and the degree of seizure protection. Impairment of rotarod performance and marked ataxia occurred at plasma valproic acid concentrations above 510 microgram ml-1 and loss of righting reflex became evident at 970 microgram ml-1. From these results, it is concluded that the plasma concentration of valproic acid is closely correlated with the anticonvulsant and neurotoxic effects observed in individual rats after acute administration of sodium valproate.     

利伐沙班治疗老年非瓣膜性心房颤动患者的有效性及安全性分析

目的探讨老年非瓣膜性心房颤动患者采用利伐沙班治疗的有效性及安全性。方法60例老年非瓣膜性心房颤动患者,依据抗凝治疗方法不同分为利伐沙班组和华法林组,各30例。利伐沙班组患者接受利伐沙班抗凝治疗,华法林组患者接受华法林抗凝治疗。比较两组患者的栓塞事件、出血事件、不良反应发生情况。结果利伐沙班组患者的栓塞事件发生率为10.0%(3/30),华法林组患者的栓塞事件发生率为13.3%(4/30),两组比较差异无统计学意义(P>0.05)。利伐沙班组患者的出血事件发生率为3.3%,低于华法林组的20.0%,差异具有统计学意义(P<0.05)。利伐沙班组患者的不良反应发生率为16.7%,低于华法林组的40.0%,差异具有统计学意义(P<0.05)。结论老年非瓣膜性心房颤动患者采用利伐沙班抗凝治疗的有效性及安全性较华法林高,更能有效降低患者的出血事件、不良反应发生率,值得推广。     

The plasma concentration and LDL-C relationship in patients receiving ezetimibe

Ezetimibe is a novel selective inhibitor of intestinal cholesterol absorption, which has been shown to significantly decrease low-density lipoprotein cholesterol (LDL-C). In this article, the relationship between plasma ezetimibe concentrations and lowering of LDL-C is determined using Emax and regression models. Data from two phase II double-blind placebo-controlled studies (n = 232 and 177) were used in which daily doses of ezetimibe ranging from 0.25 to 10 mg were administered for 12 weeks. Ezetimibe concentrations correlated significantly with percentage change in LDL-C from baseline (%LDL-C). Reductions in %LDL-C of 10%, 15%, and 20% were achieved with concentrations in the ranges 0 to 2, 2 to 15, and > 15 ng/ml, respectively, as compared with placebo. To achieve > 15% reduction in LDL-C, patients need to maintain trough concentrations > 15 ng/ml, taking plasma concentrations as a surrogate for concentrations at the enterocyte. Based on the doses administered, the 10 mg dose had the highest likelihood of sustaining such concentrations, confirming that a daily 10 mg dose of ezetimibe is an optimal therapeutic dose in the treatment of hypercholesterolemia.     

疏血通治疗慢性肺心病并发阵发性房颤的效果和 安全性观察

目的 探讨疏血通注射液治疗慢性肺源性心脏病（肺心病）并发阵发性房颤的临床疗效及安全性。方法 将 91 例慢性肺心病并发阵发性房颤患者随机分为治疗组 45 例和对照组 46 例, 对照组在常规治疗（吸氧、 祛痰、 平喘） 的基础上给予氯吡格雷 75 mg 口服, 治疗组在对照组基础上加用生理盐水 250 mL+疏血通 6 mL 静脉滴注,均 1 次/d, 应用 14 d。检测 48 h 内阵发性房颤转复为窦性心律的时间; 用药 48 h 及 14 d 时阵发性房颤转复窦性心律维持例数; 于治疗前及治疗 14 d 时采用胶体金法检测 D-二聚体（D-Dimer）, 并监测肝、 肾功能及药物不良反应。结果 治疗组在 48 h 内阵发性房颤转复为窦性心律的时间与对照组差异无统计学意义（h： 12.62±2.32 vs 13.32± 2.25, t=1.461）; 治疗组用药 48 h 及 14 d 时阵发性房颤转复窦性心律维持率分别是 86.67%（39/45）、 82.22%（37/45）,均高于对照组的 69.56%（32/46）、 60.87%（28/46）。治疗 14 d 时, 治疗组 D-Dimer[(2.05±0.34)mg/L]较治疗前[(2.61± 0.27)mg/L]降低, 且低于对照组[(2.53±0.31)mg/L] （均 P＜0.05）。2 组治疗期间均未出现肝、 肾功能异常, 且均未发生不良反应。结论 疏血通注射液联合氯吡格雷口服可防治慢性肺心病患者阵发性房颤的复发, 降低血栓栓塞的风险, 安全有效。     

Patient-reported treatment satisfaction with rivaroxaban in Japanese non-valvular atrial fibrillation patients: an observational study

Objectives: Rivaroxaban has previously been shown to be as efficacious and safe as warfarin for the prevention of stroke in non-valvular atrial fibrillation (NVAF). Therefore, treatment satisfaction becomes an important consideration. Here we examine treatment satisfaction in Japanese NVAF patients who were switched from warfarin to rivaroxaban.

Methods: Patient-reported outcome (PRO) data were collected as part of a prospective, multi-center, post-marketing surveillance (PMS) of a direct oral-anticoagulant, rivaroxaban, in Japan. The Anti-Clot Treatment Scale (ACTS) and the Treatment Satisfaction Questionnaire for Medication version II (TSQM-II) were collected at baseline, month 3, and month 6. Change in scores from baseline to month 3 and month 6 were assessed. Exploratory analyses included change in scores by patient characteristics. Safety and effectiveness of rivaroxaban were also assessed.

Results: ACTS Burdens scores significantly improved at month 3 (54.6?±?6.3) and month 6 (54.5?±?6.5) compared to baseline (51.0?±?7.6) (p?<?.001). ACTS Benefits score remained stable over time (baseline?=?10.1?±?2.8, month 3?=?10.2?±?3.1, month 6?=?10.1?±?3.1). Mean TSQM-II sub-scale scores significantly improved at month 3 and month 6 compared to baseline for all four domains (all p?<?.001).

Conclusions: Findings suggest treatment satisfaction may improve in Japanese NVAF patients after a switch from warfarin to rivaroxaban. Higher treatment satisfaction may translate into improved treatment adherence, which is critical for the long-term prevention of stroke.