The Effect of Age and Everyday Exercise on Steady-State Plasma Digoxin Concentrations

Age-related physiologic changes may significantly alter the disposition and pharmacologic characteristics of many drugs. The elderly are the most frequent users of digoxin because of increased prevalence of atrial fibrillation and congestive heart failure. This study was conducted to confirm the decrease in digoxin concentrations during exercise, to determine if age is a factor in this decrease, and to explore the difference between chronologic age and physiologic age. Eighteen men age 50–85 years were treated with digoxin for more than 1 month before enrolling and had serum digoxin concentrations of 0.4-2.0 μg/L. They were evaluated during a 3-hour period in the morning (A.M. dose withheld). Blood samples were obtained every 10 minutes during sequential 60-minute periods of rest (phase I), walking (phase II), and rest (phase III). There were no significant differences in mean concentration between phases II and I (p<0.76), phases III and phase I (p<0.70), or phases II and III (p<0.37). The effect of age was positively correlated with the mean concentration of phase II but was not statistically significant (p<0.62). Statistically significant correlations were seen only between the exercise phase and serum albumin and Mini-Mental Status Examination scores. We conclude that exercise has minimal, if any, clinically relevant effects on plasma digoxin concentrations. Increasing chronologic age has no influence on a decrease in the concentrations with exercise; a younger physiologic age may play a role.     

The Effect of Fluvastatin on Plasma Fibrinogen Levels

Summary

There are conflicting data with regard to the effect of statins, including fluvastatin, on plasma fibrinogen levels. We undertook the present study to examine the influence of fluvastatin (40mg/day) on plasma fibrinogen levels in hypercholesterolemic non-smoker patients with normal triglyceride levels (< 2.25mmol/l) (n?=?65). Fluvastatin administration was followed by a significant decrease of plasma fibrinogen levels by 8% (from 3.6g/l to 3.33g/l median value, p?<?0.02). No correlation was found between the change in lipids and that in fibrinogen levels. Furthermore, there was no correlation between plasma fibrinogen levels and the change in fibrinogen concentration after fluvastatin administration.

These results are in contrast with previously published data. However, the majority of the previous studies included patients with ischemic heart disease, unlike our study population. Furthermore, in some of these studies, which included relatively small numbers of patients, there was a trend towards a decrease in plasma fibrinogen concentration after fluvastatin administration.

We conclude that fluvastatin can significantly decrease plasma fibrinogen levels. However, more studies using fluvastatin and other drugs of this class are necessary to clarify this issue.     

Bimodal Effect of Lithium Plasma Levels on Hippocampal Glutamate Concentrations in Bipolar II Depression: A Pilot Study

Background:

The hippocampus has been highly implicated in the pathophysiology of bipolar disorder (BD). Nevertheless, no study has longitudinally evaluated hippocampal metabolite levels in bipolar depression under treatment with lithium.

Methods:

Nineteen medication-free BD patients (78.9% treatment-naïve and 73.7% with BD type II) presenting an acute depressive episode and 17 healthy controls were studied. Patients were treated for 6 weeks with lithium in an open-label trial. N-acetyl aspartate (NAA), creatine, choline, myo-Inositol, and glutamate levels were assessed in the left hippocampus before (week 0) and after (week 6) lithium treatment using 3T proton magnetic resonance spectroscopy (1H-MRS). The metabolite concentrations were estimated using internal water as reference and voxel segmentation for partial volume correction.

Results:

At baseline, acutely depressed BD patients and healthy controls exhibited similar hippocampal metabolites concentrations, with no changes after 6 weeks of lithium monotherapy. A significant correlation between antidepressant efficacy and increases in NAA concentration over time was observed. Also, there was a significant positive correlation between the changes in glutamate concentrations over follow-up and plasma lithium levels at endpoint. Mixed effects model analysis revealed a bimodal effect of lithium plasma levels in hippocampal glutamate concentrations: levels of 0.2 to 0.49mmol/L (n=9) were associated with a decrease in glutamate concentrations, whereas the subgroup of BD subjects with “standard” lithium levels (≥0.50 mmol/L; n = 10) showed an overall increase in glutamate concentrations over time.

Conclusions:

These preliminary results suggest that lithium has a bimodal action in hippocampal glutamate concentration depending on the plasma levels.     

Lithium and Valproate Combined Administration: Acute Behavioural Effects and Drug Plasma Levels

Abstract: Drug plasma concentrations and behavioural effects of acute combined administration of lithium and valproic acid were studied in normonatraemic and hyponatraemic rats. Hyponatraemia was induced two hours before drug administration and behavioural observations lasted for two additional hours. Blood was collected by the end of the behavioural observation. The higher doses of valproic acid (360 mg/kg) or lithium (2 mEq/kg) induced more head-shakes and higher plasma concentration than 180 mg/kg of valproic acid or lithium 1 mEq/kg, respectively. Valproic acid and lithium administered separately induced more head shakes and higher drug plasma levels in hyponatraemic rats than in normonatraemic animals. Combined administration of valproic acid (180 mg/kg) and lithium (2 mEq/kg) produced a supra-aditive effect in head-shakes. The drug interaction between lithium and valproic acid induced a decrease in valproic acid plasma level and an increase in lithium plasma levels.     

The Effect of Supplemental Dietary Fat on Plasma Cholesterol Levels in Lovastatin-Treated Hypercholesterolemic Patients

Study Objective . A validation study was conducted first to test assumptions about the effect of saturated and unsaturated dietary fat supplements. The second study was conducted to determine the effect on blood cholesterol levels of saturated and unsaturated fat supplements in patients who followed a low-fat diet and were administered lovastatin. Design . Randomized, crossover design, with three periods in the first study and four in the second study, each lasting 6 weeks. Setting . Cholesterol Research Center. Patients . The first study evaluated adults with total cholesterol levels between 200 and 280 mg/dl (5.172 and 7.241 mmol/L). The second study included adults with low-density lipoprotein (LDL) cholesterol levels above 160 mg/dl (4.138 mmol/L). Interventions . Fat supplements with either coconut or canola oil were delivered to patients in oatmeal-raisin cookies. Measurements and Main Results . In the validation study, patients' mean prerandomization total cholesterol level of 222 mg/dl was reduced to 213 mg/dl with canola oil and increased to 233 mg/dl with coconut oil cookies (p=0.0038). In the second study the mean prerandomization total cholesterol level of 214 mg/dl was decreased to 199 mg/dl with canola oil and to 208 mg/dl with coconut oil cookies (p=0.2342). The LDL cholesterol levels changed in a similar fashion in both studies. Conclusions . Changes in total and LDL cholesterol levels in the validation study were expected based on established effects of saturated and unsaturated fatty acids, but changes in these levels in lovastatin-cookie study were not expected. They could have occurred because lovastatin reversed the effect of saturated fats and enhanced the effect of unsaturated fats. Alternatively, they may have been due to enhanced bioavailability of lovastatin when administered with a high-fat diet. These findings must be confirmed.     

RP-HPLC法测定人血浆中氟比洛芬的浓度

目的:建立以反相高效液相色谱法测定人血浆中氟比洛芬浓度的方法。方法:采用外标法,以乙腈沉淀法处理样品后进样测定,色谱柱为Symmetry shield C_(18),流动相为磷酸盐缓冲液(pH7.0):乙腈=75:25,流速为1.0 mL·min~(-1),紫外检测波长为247 nm。结果:氟比洛芬血药浓度在0.05～20μg·mL~(-1)范围内线性关系良好(r=0.999 1),检测限为0.05μg·mL~(-1);低、中、高浓度的回收率在96.1%～107.1%之间,日内及日间RSD均<10%,符合方法学要求。结论:本方法简便、准确、快速,适用于人血浆中氟比洛芬浓度监测及药动学研究。     

Comparison of Single-Dose and Steady-State Nadolol Plasma Concentrations

The pharmacokinetics of nadolol have been previously reported to be linear between single and steady-state dosing. Data from a study in our laboratory suggested greater than expected -blockade with nadolol at steady state. Because the early potency studies were single-dose studies, we hypothesized there was a nonlinearity in nadolol pharmacokinetics which produced higher than expected plasma concentrations at steady state. Six normal volunteers from the previous study (steady state) volunteered to participate in the single-dose study. Plasma concentrations were determined for 24 hr following a single dose of nadolol, 80 mg. A simple, inexpensive, and accurate method for determination of nadolol in plasma or serum by HPLC with fluorometric detection is described. The AUC_o–tau at steady state was greater than the AUC_0– following a single dose in five of the six subjects. The mean ratio of AUC_ss/AUC_sd was 2.54. This value would be unity in the presence of linear pharmacokinetics. We conclude that the principle of superposition is not applicable for nadolol.     

Acute Effect of Inragastric Ethanol Administration on Plasma Levels of Stress Hormones

We have previously demonstrated that single-dose ethanol administration enhanced plasma levels of ACTH, β-endorphin, corticosterone (CS) and catecholamines. Since the secretion of proopiomelanoncortin-derived peptides (e.g., ACTH, β-endorphin) can be influenced by catecholamines and vasopressin in addition to the primary physiological regulator, corticotrophin-releasing hormone, we have attempted to determine whether or not the ethanol-induced activation of the hypothalamic-pituitary-adrenal axis (HPAA) could in part be mediated via either epinephrine or vasopressin (AVP) secretion. The selective neutralization of AVP through the administration of AVP antiserum failed to block the ethanol-induced secretion of either ACTH or CS. In addition, adrenal demedullation did not significantly attenuate the ethanol-induced increase of ACTH and CS. It would appear that neither adrenal medulla-derived epinepherine nor median eminence-derived AVP mediates ethanol's activation of the HPAA.     

临床药师干预氟比洛芬酯注射液合理使用的效果分析

摘 要 目的： 评价临床药师干预前后,氟比洛芬酯注射液用药不合理现象的改善情况。方法: 调取2014年1月我院住院部氟比洛芬酯注射液用量及使用情况详细数据进行点评,干预后采用相同方式调取2014年7月氟比洛芬酯注射液用药数据进行分析对比。结果: 临床药师干预后,盐酸氟比洛芬酯注射液用量有所下降（20.6%）,各个科室用药剂量有所下调、疗程缩短,该药物的使用费用下降,疼痛评估情况也有所改善,部分外科科室已经建立了根据患者疼痛评估结果调整药物使用的意识。结论: 通过临床药师干预,我院氟比洛芬酯注射液用药不合理现象有所改善,但仍存在一些问题,需要持续改进。     

氟比洛芬酯对兔腰椎间盘突出症的影响

目的:观察氟比洛芬酯注射液(flurbiprofen axetil injection,FAI)对腰椎间盘突出症兔椎间盘髓核组织中磷脂酶A2(PLA2)、前列腺素E2(PGE2)水平的影响,探讨FAI对腰椎间盘突出症的治疗作用及其机制。方法:雄性6月龄新西兰大白兔,于L3-4和L4-5节段椎间盘用18G针头行纤维环穿刺,制作兔腰椎间盘突出症动物模型。术后3周行计算机断层扫描(CT)检查,确认造模成功32只,随机分为治疗组和对照组,每组16只。采用硬膜外注射给药,治疗组注射FAI,对照组注射等量生理盐水。比较治疗前后的自由行走痛行为学评分;治疗结束后第7天处死动物,获取椎间盘组织,ELISA法测定其中的PLA2、PGE2水平,HE染色行形态学学观察。结果:与对照组比较,治疗后痛行为学评分治疗组显著下降(P<0.05),治疗组椎间盘髓核组织中PLA2和PGE2水平显著降低(P<0.05);HE染色显示:对照组椎间盘髓核及纤维环组织内可见肉芽组织生长,并有大量炎性细胞浸润;治疗组椎间盘髓核及纤维环组织内无肉芽组织生长及炎性细胞浸润。结论:FAI能显著降低腰椎间盘突出症兔椎间盘髓核组织中PLA2和PGE2水平,降低腰椎间盘组织病理损伤,在椎间盘突出症的治疗中发挥抗炎镇痛作用。     

体重与伏立康唑稳态血药谷浓度的相关性分析

目的分析临床患者体重与伏立康唑稳态血药谷浓度的相关性。方法采用HPLC 法对57 例使用伏立康唑静脉滴注治疗的患者进行稳态血药谷浓度测定, 分析其与体重的相关性。结果在使用200 mg、q12 h 维持剂量的伏立康唑时,随体重增加,伏立康唑稳态血药谷浓度呈降低趋势;70 －80 kg 体重患者中采用300 mg、q12 h 的维持剂量患者的稳态谷浓度明显高于采用200 mg、q12 h 维持剂量的患者（P 〈0. 01）。结论体重与伏立康唑稳态血药谷浓度有一定相关性。     

培哚普利对急性冠脉综合征患者血清C-反应蛋白的影响

目的:观察培哚普利对急性冠脉综合征(ACS)患者血清C-反应蛋白(CRP) 的影响. 方法:ACS住院患者60例,其中急性心肌梗死(AMI)患者30例,不稳定型心绞痛(UA)患者30例,依数字随机法分为AMI治疗组(15例),AMI对照组(15例),UA治疗组(15例)和UA对照组(15例).对照组给予常规治疗,治疗组在常规治疗基础上加用培哚普利口服,检测患者治疗前后CRP含量,并分组比较.结果:60例ACS患者治疗后血清CRP均显著下降(P＜0.05),但治疗组与对照组比较CRP 水平下降无显著差异(P＞0.05).结论:培哚普利在短期内对炎症反应的影响不明显.     

氟比洛芬酯联合右美托咪定预防 瑞芬太尼麻醉后痛觉过敏

目的： 探讨氟比洛芬酯联合右美托咪定用于预防瑞芬太尼麻醉后痛觉过敏的临床效果及安全性。方法：选择我院2016年1月至2016年6月行腹腔镜胆囊切除术的患者80例,随机平均分为对照组、氟比洛芬酯组、右美托咪定组和联合用药组。根据各组的预防给药方式进行干预,记录患者术后1、2、6、12、24 h的VAS评分、术后 24 h镇痛药物追加情况及寒颤、恶心呕吐、躁动等不良反应的发生率。结果：联合用药组术后各时间点的VAS评分均明显低于单独用药组和对照组;右美托咪定组和联合用药组发生躁动的例数明显低于对照组;联合用药组24 h内追加镇痛药物的发生率明显低于其他3组（P<0.05）。结论：氟比洛芬酯联合右美托咪定能降低瑞芬太尼麻醉后痛觉过敏的发生,同时显著降低术后追加镇静药物和躁动的发生率,比单独用药疗效更佳。     

精神分裂症患者氯氮平血药浓度的研究

目的：探讨氯氮平血药浓度与其抗精神分裂症治疗疗效的关系。方法：抽取80例精神分裂症患者,给予氯氮平≥400mg/d治疗8周。治疗前后用简明精神病评定量表（BPRS）评定氯氮平疗效,按BPRS减分率≥20％和＜20％分为有效组和无效组。氯氮平血浆血药浓度用高效液相色谱分析法测定。结果：采用x^2检验进行分析。结果80例患者中76例完成了整个试验,其结果分析表明在氯氮平治疗第4周的血药浓度与BPRS疗效评价没有明显关系,而在治疗后第8周血药浓度＞350ng/ml治疗组疗效显著（P＜0.05)。结论：氯氮平治疗第8周血药浓度与临床疗效有明显相关性。     

血浆网膜素水平与代谢综合征的关系研究

目的:探讨2型糖尿病(T2DM)合并代谢综合征(MS)患者血浆网膜素水平的变化.方法:收集T2DM患者95例和正常对照(NC)组36例,将T2DM患者分为T2DM不合并MS组(A组)46例,T2DM合并MS组(B组)49例.采用ELISA检测3组空腹血浆网膜素水平,检测各组血糖、血脂、空腹胰岛素(Fins)、收缩压(SBP)、舒张压(DBP),计算腰臀比(WHR)、体质量指数(BMI),胰岛索抵抗指数(HOMA-IR),并分析各指标与网膜素的关系.结果:血浆网膜素水平NC组最高,A组其次,B组水平最低;其与腰围(WC)、臀围(HC)、BMI、三酰甘油(TG)、空腹血糖(FBG)、75 g葡萄糖负荷后2 h血糖(2hPG)、Fins、HOMA-IR、SBP、DBP呈负相关(r分别为-0.465、-0.473、-0.814、-0.696、-0.380、0.635、-0.691、-0.684、-0.663、-0.522,P＜0.01),与高密度脂蛋白胆固醇(HDL-C)呈正相关(r=0.279,P＜0.01).BMI、2hPG和WC是空腹血浆网膜素的影响因素.结论:MS患者血浆网膜素水平与胰岛素抵抗和肥胖密切相关,可能在MS的发病过程中起到重要作用.     

Does Acyclovir Increase Serum Lithium Levels?

A 42-year-old woman was admitted to the hospital to receive intravenous acyclovir for a herpes zoster infection. At the time she was taking lithium carbonate 450 mg twice/day. Six days after starting acyclovir she exhibited signs of lithium toxicity. When measured, the serum lithium level had increased 4-fold during acyclovir therapy. Both agents are excreted by the kidneys, raising the possibility that acyclovir at high serum concentrations may interfere with the renal excretion of lithium. A MEDLINE search did not identify any citation describing the possibility of an interaction between the drugs. This case suggests that acyclovir when given intravenously in doses of 10 mg/kg may result in increased serum lithium concentrations. Until additional data are available, if intravenous acyclovir is administered concurrently with lithium, we recommend closely monitoring patients for signs of lithium toxicity and measuring serum lithium levels every second or third day.     

氟比洛芬酯超前镇痛对颅脑手术患者细胞因子水平的影响

目的:研究氟比洛芬酯对颅脑手术患者超前镇痛效果及对围术期血清炎性细胞因子水平的影响.方法:选择神经外科手术患者40例,ASA Ⅰ～Ⅱ级,随机分为C组和F组,每组20例.采用双盲法分别于气管插管后(切皮前15min)静脉注射氟比洛芬酯10mL(F组)或安慰剂(C组)10mL.记录术后2、24、48 h的镇痛评分(VAS值).在麻醉开始前(T1)、手术2 h(T2)、术毕(T3)及术后24 h(T4)测血清肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6和IL-10含量.记录麻醉时间、术中出血量、尿量和手术输液量及瑞芬太尼和丙泊酚用量.结果:(1)术后2 h和24 h的VAS评分F组均较C组明显减低(P＜0.05).(2)F组瑞芬太尼和丙泊酚用量较C组明显降低(P＜0.05).(3)与T1比较,2组T2、T3时点血清TNF-α含量均明显升高(P＜0.05),且在T2时点达高峰;与C组比较,F组T2～T4时点血清TNF-α含量明显降低(P＜0.05).与T1比较,2组T2～T4时点血清IL-6、IL-10含量均明显升高(P＜0.05),且在T3时点达高峰;与C组比较,F组T2～T4时点血清IL-6含量降低、IL-10含量升高(P＜0.05).结论:术前预给氟比洛芬酯注射液具有确切的超前镇痛作用,并能降低颅脑手术围手术期应激炎性反应.     

氟比洛芬酯对手术致痛大鼠行为学的影响

目的观察氟比洛芬酯对手术致痛大鼠行为学的影响。 方法将48只SD大鼠随机分为6组。对照1（D1）组大鼠单纯吸入异氟醚麻醉,不进行手术,其余5组（D2、K1～K4组）以异氟醚吸入使大鼠麻醉,按BRENNAN 法手术,建立大鼠手术切口疼痛模型。20 min后经尾静脉给药。D1组、D2组大鼠给予0.9%氯化钠注射液,K1～K4组分别给予氟比洛芬酯注射液2,4,8,16 mg·kg 1。待大鼠手术清醒及每组给药后1 h,进行累积疼痛评分,观察给药后反应。结果氟比洛芬酯可剂量依赖性地降低切口疼痛模型大鼠的累积疼痛评分(P＜0.05)。 结论氟比洛芬酯可抑制外科手术的疼痛反应,并呈一定的剂量依赖性。     

基于径向基神经网络的舒必利稳态血药浓度预测

目的建立基于径向基（RBF）神经网络舒必利稳态血药浓度预测模型。方法将所收集的用于建立舒必利稳态血药浓度预测模型的数据（包括患者的性别、年龄、体重、剂量、稳态血药谷浓度、多项生理生化指标等）分为训练集、校验集和测试集,前两者用于训练RBF神经网络,后者用于测试RBF神经网络,分别利用各数据集的网络计算输出值与目标输出值之间的均方差（MSE）和相关系数（R）评价网络模型的训练效果和预测性能。结果建立以患者的性别、年龄、体重、剂量、多项生理生化指标等37项参数为输入变量,舒必利稳态血药浓度为输出变量的37—1—1结构的RBF神经网络,当网络中心宽度SP值为2．3时,训练集、校验集和测试集的MSE分别为4．50×10^-6、0．003531和0．011001,R值分别为0．99991、0．95532和0．81425。结论利用RBF神经网络所建立的舒必利稳态血药浓度预测模型的预测效果较好,但泛化能力尚待提高。     

The Effect of Niceritrol (Pentaerythritoltetranicotinate) on Experimental Atherosclerosis in Cholesterol-fed Rabbits at Different Levels of Plasma Cholesterol

The action of the hypolipaemic drug niceritrol (INN) on cholesterol accumulation in the aorta was studied in cholesterol-fed rabbits at three levels of plasma cholesterol, approximately 100, 500–1000 and 2000 mg/100 ml. This was achieved by feeding diets with three different concentrations of cholesterol. The two higher but not the lowest concentration resulted in a large increase in plasma cholesterol as well as in a moderate lipid infiltration of the aorta. On addition of 0.5–1% niceritrol to the diet there was a significant reduction of plasma cholesterol in all three series. In the series with the lowest plasma cholesterol level the degree of atherosclerotic changes were so slight that the effect of niceritrol could not be evaluated. In the series with plasma cholesterol up to 1000 mg/100 ml niceritrol markedly inhibited the lipid infiltration of the aorta. In the series with the highest plasma cholesterol level niceritrol had no protective effect. The relationship between plasma cholesterol levels and extent of aortic lipid infiltration was studied in a pooled reference material of 154 cholesterol-fed rabbits. The demonstrated type of relationship could largely explain the difference in the protective action of niceritrol in the three series.