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1.
The pharmacokinetics of theophylline (Uniphyllin) in blood and saliva was compared after morning and evening administration of a once-daily dose in a randomized cross-over study. Ten bronchial asthma patients received multiple doses of 800 mg theophylline at 8 a.m. and 8 p.m. under controlled food conditions. The precision of the serum concentration prediction from salivary measurements in individual patients was sufficient to obtain identical pharmacokinetic parameters and parallel concentration-time curves. There were no significant differences in the values of mean residence time and area under the concentration-time curves after morning and evening dosing, either in the kinetics of elimination and in the volume of distribution. The fluctuation of concentrations during the dosing intervals was 100% after morning doses and 80% after evening doses. No consistent interference with food was found. Circadian variation in the kinetics of drug disposition after once-daily theophylline administration did not occur. In order to achieve higher therapeutical levels at night and in the morning, the evening dosing seems to be preferable.  相似文献   

2.
PURPOSE: The pharmacokinetics and safety of 1000-mg extended-release divalproex sodium given once daily either in the morning or evening were compared. METHODS: Healthy volunteers 19-55 years of age were enrolled in this open-label, parallel-design study. Subjects were randomized to receive extended-release divalproex either in the morning or in the evening. Blood samples were taken immediately before and at 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 121, 122, 123, 124.5, 126, 127.5, 129, 130.5, 132, 133, 134, 135, 136.5, 138, 139.5, 141, 142.5, and 144 hours after the first dose of each six-day regimen. Plasma samples were assayed for total valproic acid concentrations using gas chromatography. Valproic acid pharmacokinetic values were measured, and the safety of each regimen was evaluated. RESULTS: Mean steady-state valproic acid exposure, maximum concentration, and minimum concentration were 1771 mg x hr/L, 86.9 mg/L, and 55.5 mg/L for the morning dosing and 1728 mg x hr/L, 84.8 mg/L, and 57.4 mg/L for the evening dosing regimens, respectively. Adverse events reported by two or more subjects were abdominal pain and somnolence for the morning dosing regimen and asthenia, headache, and pain for the evening dosing regimen. All adverse events were mild or moderate; none caused subject withdrawal from the study. There were no significant differences in the pharmacokinetic parameters (p > 0.51) and safety between groups. Diurnal variation in plasma valproic acid concentrations was minimal with once-daily administration of extended-release divalproex. CONCLUSION: Evening once-daily administration of extended-release divalproex was not associated with substantial differences in pharmacokinetics or safety compared with morning once-daily administration.  相似文献   

3.
ABSTRACT

Objective: To compare the IOP-lowering efficacy of a.m.-dosed travoprost and latanoprost at 24-h post-dose.

Research design and methods: Open-angle glaucoma patients not naïve to prostaglandin therapy and currently controlled on p.m.-dosed (2100) latanoprost (n?=?21) or travoprost (n?=?30) had baseline IOPs measured at 0900. In a randomized, single-masked, crossover design, patients received travoprost (Travatan) or latanoprost (Xalatan) at 0900 for 4?weeks, then were crossed over to receive the second prostaglandin for another 4?weeks. Treatment IOP was measured at 0900 prior to morning dose at both 4 and 8?week visits. Patient dosing preference (a.m./p.m.) was surveyed on exit.

Main outcome measure: Intraocular pressure (IOP).

Results: The mean IOP in the first period when all patients were dosed in the evening was assessed 12?h after dosing at 09:00 and it was similar in the two treatment groups (mean?±?standard deviation: 17.9?±?2.7?mmHg for travoprost versus 17.7?±?2.5?mmHg for latanoprost, p?=?0.812). In the a.m.-dosing crossover comparison, the 24-h post-dose IOP was significantly lower (?p?<?0.001) on travoprost (16.9?±?3.1?mmHg) compared to latanoprost (18.6?±?3.3?mmHg). In the exit survey, 51% of patients preferred a.m.-dosing.

Conclusions: a.m.-dosed travoprost is superior to a.m.-dosed latanoprost by 1.7?mmHg at 24-h post-dose.  相似文献   

4.
5.
In order to determine whether there is a difference in the effect of the hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pravastatin on cholesterol synthesis between the morning and the evening, we studied the 24-h profile of mevalonate in plasma and urine in 11 subjects with heterozygous familial hypercholesterolaemia. In study 1, eight subjects with familial hypercholesterolaemia took pravastatin (20 mg) once in the morning, and another 20-mg dose in the evening after a 1-week wash-out period. In study 2, five subjects with familial hypercholesterolaemia took pravastatin (20 mg per day) in the morning on 3 consecutive days and on 3 days in the evening after a 1 day wash-out. Plasma mevalonate concentrations were reduced at 9 h and 5 h after pravastatin administration in the morning and the evening, respectively. Urinary mevalonate excretion was significantly reduced at 4–8 h after pravastatin administration in the morning (51 vs 19 nmol · h–1) and at 4–16 h after pravastatin administration in the evening (56 vs 27 nmol · h–1). Daily urinary mevalonate excretion was equally and significantly reduced by pravastatin in the morning or evening. In conclusion, we found that morning and evening administration of pravastatin caused equal reductions in plasma and urinary mevalonate concentrations.  相似文献   

6.

Objective:

The objective of the study was to evaluate the safety and efficacy of atorvastatin compared with simvastatin and pravastatin in patients of hyperlipidemia.

Materials and Methods:

This was a randomized, parallel group, open-label study conducted at KG hospital, Coimbatore, Tamilnadu, India. Twenty hyperlipidemia patients each taking atorvastatin 20 mg, pravastatin 20 mg and simvastatin 20 mg tablets were selected for the study after clinical and baseline investigations. The patients were reviewed after 3rd and 5th month of statin therapy for lipid profile. The liver enzyme levels (SGOT, SGPT, ALP), albumin, bilirubin, protein and biochemical infraction parameters (Creatine Kinase, Creatine Kinase - Myocardial Band) after 5th month of treatment with statins were also reviewed.

Results:

The results showed that atorvastatin significantly reduced the lipid levels (LDL-C, TC, TG, VLDL) when compared to simvastatin and pravastatin after 3rd and 5th month of treatment. Atorvastatin increased the HDL-C levels significantly when compared to simvastatin and pravastatin after 5 months of treatment. Atorvastatin also significantly reduced the CK levels when compared to pravastatin but no increase in liver enzyme levels was observed.

Conclusion:

The study showed that atorvastatin is more effective when compared to simvastatin and pravastatin in patients with hyperlipidemia.KEY WORDS: Creatine kinase, creatine kinase - myocardial band, pravastatin, simvastatin  相似文献   

7.
Combined statin and fibrate therapy is often imperative for the improvement of the serum lipid profile in patients with mixed hyperlipidemia. However, the potential risk of myopathy has limited the widespread use of such therapy. Preferably this treatment should involve low optimally tolerable doses of hypolipidemic drugs. Thus, we undertook a study to determine the safety and efficacy of combination therapy with fibrates and small doses of atorvastatin. Twenty-two patients with mixed hyperlipidemia were started on a fibrate regimen (micronised fenofibrate 200mg/day or ciprofibrate 100 mg/day). Because after 12 weeks of therapy the fibrate failed to normalise the serum lipid profile, small doses of atorvastatin (5 mg/day) were added for a further 12 weeks. The administration of the fibrates resulted in a significant decrease in total and LDL-cholesterol levels, as well as in triglycerides, and an increase in HDL-cholesterol levels. The addition of atorvastatin (5 mg/day) resulted in a further decrease in total and LDL-cholesterol levels. Consequently, the hypolipidemic therapy target was achieved in most of the patents. Combination therapy was well tolerated and no significant increases in serum liver and muscle enzymes were noticed. We conclude that the careful administration of small doses of atorvastatin in patients with mixed dyslipidemia receiving fibrates is associated with a significant amelioration of lipid abnormalities.  相似文献   

8.
目的 对比不同剂量阿托伐他汀对高脂血症合并2型糖尿病患者的调脂效果。方法 选择2014年1月-2016年12月在青海省心脑血管病专科医院诊治的高脂血症合并2型糖尿病患者140例作为研究对象,根据随机原则分为观察组与对照组各70例,对照组给予小剂量阿托伐他汀治疗,观察组给予大剂量阿托伐他汀治疗,都治疗观察4周。比较两组糖脂代谢指标,血脂指标及并发症情况。结果 观察组与对照组治疗后的血糖与糖化血红蛋白明显低于治疗前,差异有统计学意义(P<0.05);两组治疗后的血糖与糖化血红蛋白值对比无明显差异。观察组与对照组治疗后的三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)低于治疗前,高密度脂蛋白(HDL-C)高于治疗前,对比差异明显(P<0.05);同时治疗后观察组的TG、TC、LDL-C明显低于对照组,HDL-C明显高于对照组,差异有统计学意义(P<0.05)。治疗后观察组与对照组的总有效率分别为95.7%和97.1%,两组对比差异无统计学意义;治疗后随访调查6个月,观察组的心律失常、心衰、心源性休克等并发症发生率为8.6%,对照组为27.1%,观察组明显少于对照组,差异有统计学意义(P<0.05)。结论 阿托伐他汀治疗高脂血症合并2型糖尿病患者具有很好的效果,特别是大剂量阿托伐他汀的应用具有更好的调脂效果,从而减少随访心血管并发症的发生,有很好的应用价值。  相似文献   

9.
李沂  陈伟 《现代医药卫生》2012,28(3):329-330
目的 观察阿托伐他汀(立普妥)治疗冠心病伴高脂血症的临床效果.方法 选择2009年1月至2011年3月冠心病伴高脂血症患者120例为观察对象,随机分为观察组60例和对照组60例,两组均按冠心病伴高脂血症常规内科治疗,观察组加用阿托伐他汀10 mg,1次/天口服,疗程12周,统计分析治疗前后两组血脂水平变化及心绞痛,心律失常发作次数、心力衰竭及脑卒中事件,不良反应等情况.结果 观察组治疗后总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)及甘油三酯(triacylgly cerol,TG)水平均较治疗前下降显著,而高密度脂蛋白胆固醇(high-density lipoprotein-cholesterol,HDL-C)水平升高明显(P<0.01),而对照组治疗前后TC、LDL-C及TG水平差异无统计学意义(P>0.05);观察组治疗期间平均发生心绞痛、心律失常及心力衰竭加重例数显著低于对照组,同时无脑卒中事件发生(P<0.01);观察组不良反应发生率略高于对照组,但差异无统计学意义(P>0.05).结论 阿托伐他汀能快速降低冠心病患者血脂水平,降低心脑血管事件发生,缓解冠心病患者临床症状,安全性好,可于临床广泛应用.  相似文献   

10.
目的探讨脂必泰和阿托伐他汀对C反应蛋白(CRP)的影响。方法76例高脂血症患者随机分为脂必泰组37例(口服脂必泰0.24g,每日2次,4周)和阿托伐他汀组39例(口服阿托伐他汀10mg,每晚1次。4周),治疗前后分别测定血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和高敏CRP(hsCRP)。结果4周后,两组hsCRP[分别为(3.2±0.6)mg/L、(3.1±0.7)mg/L]较治疗前[(4.4±0.5)mg/L、(4.5±0.4)mg/L]显著下降(P〈0.01);TC、TG、LDL-C均较治疗前显著下降(P〈0.01);两组治疗后HDL-C均无显著变化(P〉0.05)。结论脂必泰和阿托伐他汀不仅能调节血脂代谢,还可降低血清hsCRP浓度。  相似文献   

11.
It is well known that the sedative properties of antihistamines can differ considerably between individual drugs. Several factors have been suggested to determine the presence, absence, and/or magnitude of sedation by antihistamines. Research has suggested that the sedative effects caused by central H1 blockade partly depend on the availability of histamine competing for the same receptor and that this competition is affected by a mechanism related to sleep. Consequently, the present study was designed to compare the effects of evening and morning doses of the first-generation antihistamine hydroxyzine on cognition. It was expected that the sedative effect of hydroxyzine would be apparent in the evening after an evening dose but would be smaller in the morning after a morning dose owing to the greater release of histamine shortly after awakening. Eighteen participants (9 females) participated in a placebo-controlled, randomized, double-blind 3-way crossover design. Performance was assessed using several psychomotor tests: that is, divided attention task, critical tracking task, stop signal task, the attention network test, and the experimental attention switch task. Results demonstrated that evening doses of hydroxyzine impaired performance on the divided attention and the attention network test. Impairment after morning doses was generally larger in magnitude and affected performance measures in all tasks. It is concluded that hydroxyzine-induced impairment at tmax is more prominent after morning doses compared with evening doses and that the present study could not present direct evidence to substantiate the hypothesis that histamine availability inversely affects the magnitude of antihistamine impairment.  相似文献   

12.
Summary Possible circadian changes in the pharmacokinetics and effect on serum angiotensin-converting enzyme (ACE) activity of the ACE inhibitor enalapril have been studied in 8 healthy subjects after oral ingestion of 10 mg enalapril maleate either at 08.00 h or 20.00 h. The time to peak serum concentration (tmax) of enalapril was increased after administration at 20.00 h compared to 08.00 h (2.4 h versus 1.3 h), where as other kinetic parameters were not significantly altered. The 24 h-kinetics of the active metabolite enalaprilat did not differ significantly between the two treatments, but the area under the curve (AUC (0–24)) and the peak serum concentration (Cmax) were slightly higher after intake at 20.00 h. The relationship between the measured serum enalaprilat level and the degree of inhibition of serum ACE was the same after both treatments. Overall, the evening and morning administration of enalapril did not differ markedly in the pharmacokinetics and the time course of ACE inhibition.This report is part of the thesis to be presented by K. Weisser in partial fulfillment of the requirements for the degree of Doctor of Natural Science.  相似文献   

13.
OBJECTIVE: Monocytes that migrate into the arterial wall participate in the development and, eventually, rupture of the atherosclerotic plaque. The aim of this study was to evaluate the secretion of monocyte chemoattractant protein-1 (MCP-1) by monocytes from hyperlipidemic patients treated with hypolipidemic drugs, namely fenofibrate, simvastatin, or atorvastatin to determine what role is played by these drugs in the development and stabilization of the atherosclerotic plaque. METHODS: Fifty-four hyperlipidemic patients, who did not respond to a low-fat diet, were treated with fenofibrate, simvastatin, or atorvastatin (18 patients in each group) for 1 month. The control group included 18 normolipidemic, healthy, age-matched participants. Ten hyperlipidemic patients were effectively treated with hypolipidemic diet alone for 1 month. This group was compared with a control group of ten healthy subjects. To accurately evaluate the adhesion molecule levels, we excluded hyperlipidemic patients and control subjects with any inflammatory disease. Before and after treatment, monocytes were isolated from peripheral blood. After stimulation with lipopolysaccharide (LPS), MCP-1 secretion was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: MCP-1 levels were significantly higher in hyperlipidemic patients than controls: 15.8+/-0.47, 16.7+/-0.23, and 14.9+/-0.45 compared with 12.36+/-0.42 ng/ml. Fenofibrate, atorvastatin, and simvastatin significantly decreased MCP-1 levels from 15.8+/-0.47 to 8.79+/-0.89, from 16.7+/-0.23 to 7.46+/-0.73, and from 14.9+/-0.45 to 10.3+/-0.8 ng/ml, respectively. In the diet-treated group of hyperlipidemic patients, the level of MCP-1 before therapy was significantly higher than in controls (16.89+/-0.31 vs 12.45+/-0.36 ng/ml). The diet therapy caused a significant decrease in levels of MCP-1 to 15.1+/-0.36 ng/ml. There was a correlation between the decreased levels of lipids and the decreased release of MCP-1 in the patients treated with hypolipemic drugs. CONCLUSION: The drug-induced decrease in MCP-1 secretion in hyperlipidemic patients suggests that, apart from acting on lipids, the hypolipidemic drugs studied may directly inhibit the activity of monocytes.  相似文献   

14.
目的 探讨氨氯地平联合阿托伐他汀钙在老年高血压合并高脂血症患者中的治疗效果.方法 120例老年高血压合并高脂血症患者,随机分为对照组和实验组,每组60例.对照组采用氨氯地平片进行治疗,实验组采用氨氯地平联合阿托伐他汀钙片进行治疗.比较两组治疗前后血压(收缩压、舒张压)和血脂[总胆固醇(TC)、甘油三酯(TG)、高密度脂...  相似文献   

15.
Abstract

Objective:

Statin dose, adherence, and cardiovascular (CV) outcomes are important factors when considering switching statin therapies. The objective of the study was to compare CV event rates and risk in managed care patients receiving atorvastatin versus those switched to simvastatin from atorvastatin.  相似文献   

16.
目的 探讨瑞舒伐他汀同阿托伐他汀治疗急性冠脉综合征的临床疗效及应用价值.方法 将本院治疗的急性冠脉综合征患者随机数字表法分为两组,对照组给予阿托伐他汀治疗,观察组采用瑞舒伐他汀治疗,记录两组效果.结果 观察组治疗后总胆固醇为(4.02±0.37) mmol/L,甘油三酯为(1.85±0.13)mmol/L,低密度脂蛋白为(2.46±0.28) mmol/L,显著优于对照组(P< 0.05).观察组治疗后高敏C反应蛋白为(3.11±0.52) mg/L,IL-6为(13.44±2.35) μg/ml,与对照组比较差异有统计学意义(P<0.05).结论 瑞舒伐他汀治疗急性冠脉综合征可以有效降低患者血脂浓度,减轻患者体内血管炎症因子作用程度.  相似文献   

17.
目的 :探讨采用数学模型预测阿托伐他汀对原发性高脂血症剂量效应关系的可行性。方法:选择2016年1月至2016年12月在中国中医科学院望京医院接受阿托伐他汀的原发性高脂血症患者92例,根据患者所用药物剂量分为对照组、观察组和模型组,采用数学模型预测阿托伐他汀用药剂量与治疗原发性高脂血症效果的关系。结果:通过模型预测阿托伐他汀对原发性高脂血症患者剂量为(29.16±4.25)mg·d-1,稳态剂量为(19.45±3.56)mg·d-1。对照组、观察组和预测组患者的药代动力学参数、血药浓度、甘油三酯、总胆固醇、低密度脂蛋白胆固醇和极低密度脂蛋白胆固醇比较,差异具有统计学意义(均P<0.05)。对照组与观察组药物代谢动力学参数、血药浓度、TG、TC、LDL-C和VLDL-C比较,差异具有统计学意义(均P<0.05);对照组与模型预测组药物代谢动力学参数、血药浓度、TG、TC、LDL-C和VLDL-C比较,差异具有统计学意义(均P<0.05);观察组与模型预测组药峰浓度、半衰期和药物浓度-时间曲线下面积比较,差异具有统计学意义(均P<0.05),但相对清除率、表观分布体积、达峰时间、血药浓度、TG、TC、LDL-C和VLDL-C比较,差异无统计学意义(P>0.05)。通过构建散点图观察发现,个体预测血药浓度值与实际值均匀分散在对角线两侧。3组不良反应发生率比较,差异有统计学意义(χ2=7.038,P<0.05)。结论:采用数学模型可预测阿托伐他汀治疗原发性高脂血症患者的最佳用药剂量,从而获得较好的临床效果,可应用于临床药物剂量的估算。  相似文献   

18.
Partial food restriction (FR) protocols have been used not only to study behavioral and physiological consequences of decrease food intake, but as a necessary treatment of the animals in some operant learning tasks. It is well-established in rodents that restricting food availability to a few hours in the morning causes an alteration of the daily rhythm of corticosterone, thus making it difficult to evaluate whether or not such treatments are stressful. In the present experiment adult male Sprague-Dawley rats were subjected to two different FR schedules: food availability after 1100 h (LFR) or after 1900 h (DFR). After 14 days, animals from both groups, together with corresponding controls, were killed under resting conditions, either in the morning or in the evening, just before daily access to food in FR rats. Both FR schedules reduced body weight gain to the same extent, but their impact on the hypothalamic-pituitary-adrenal (HPA) axis was different: DFR increased relative, but not absolute, adrenal weight and morning and evening levels of corticosterone, whereas LFR increased both absolute and relative adrenal weights and increased morning corticosterone levels to a greater extent than DFR rats. Neither serum ACTH nor corticotropin-releasing factor (CRF) mRNA levels in the paraventricular nucleus of the hypothalamus were altered by DFR or LFR protocols, suggesting that factors other than CRF and ACTH are involved in the control of adrenocortical secretion under FR. It appears that LFR caused more alterations in the HPA axis than DFR and, therefore, the latter FR schedule should be used in those protocols necessarily involving partial FR.  相似文献   

19.
AIM: To assess the effect of timing of rebeprazole (RB) 20 mg/d administration on oesophageal acid exposure and nocturnal gastric acid breakthrough (NGAB) in patients with GERD. METHODS: 20 GERD patients received two 7-day treatments of RB in the morning (a.m.) or in the evening (p.m.) hours. The regimens were randomized in a double-blind fashion and separated by a 7-day washout period. The tablets were taken 30 min before standardized meals. A combined (oesophageal & gastric) 24-hour pH monitoring was performed before and on day 7 of each treatment. RESULTS: Total oesophageal acid exposure was normalized in 10/14 (71.4%) patients with RB p.m. and in 6/15 (42.8%) with RB a.m. RB p.m. significantly decreased the nocturnal supine oesophageal acid exposure vs. RB a.m., 0.2% vs. 3.4%. The mean NGAB duration was significantly shortened with RB a.m. and p.m. vs. the baseline recording, 4.1+/-1.8 and 3.4+/-1.5 hours vs. 7.8+/-1.7 hours. CONCLUSIONS: Rabeprazole significantly reduced the NGAB duration and significantly increased the mean nocturnal gastric pH; RB p.m. normalized more effectively the total oesophageal exposure than RB-a.m.; RB p.m. provided significantly better control of nocturnal supine gastro-oesophageal reflux than a.m. dosing. These data suggest that administration of a PPI before the evening meal maximizes acid control and would be the preferred dosing schedule in GERD patients, particularly those with nocturnal symptoms.  相似文献   

20.
In previous studies of psychomotor performance, the stimulant effects of caffeine differed by personality characteristics. For example, caffeine improved the task performance of extraverts but overaroused introverts and thus impaired their performance. The present study compared the effects of caffeine on subjective arousal among introverts and extraverts. Seventeen introverts and 19 extraverts drank coffee that contained doses of 0, 2, and 4 mg/kg caffeine during morning and evening sessions in a within-subjects, randomized, double-blind, crossover design. At 30-min intervals for 180 min after drinking, participants completed the Profile of Mood States, a battery of self-report visual analog scales, and the Digit Symbol Substitution Test (DSST). Caffeine effects on mood and task performance did not significantly interact with extraversion, except for nonsignificant trends for caffeine to increase happiness and vigor more among extraverts than introverts. No 3-way interactions of group, time, and dose were found on any scales or on the DSST. Results do not support the hypothesis that caffeine differentially affects extraverts and introverts, particularly at different times of the day.  相似文献   

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