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31.
32.
Jean Thiffault Hlne Landriault Denis Gossard Manon Raymond Gilles Caill Jean Spnard 《Biopharmaceutics & drug disposition》1996,17(2):107-115
Twenty-three young, healthy, male volunteers received, in a randomized crossover design, 240 mg of a once-a-day diltiazem formulation at 08:00 (AM) or 22:00 (HS) for 6 days. A 7 day washout period was observed between the two modes of administration. Diltiazem plasma concentrations were monitored every hour for 24 h and at 30, 36, and 48 h after the last dose. Differences were found between AM and HS dosing for Cmin (mean (SD)=47·2 (25·8) against 39·6 (21·1) ng mL−1, p=0·038), AUC0–24 (2008 (814) against 1754 (714) ng h mL−1, p=0·024), and AUC0–48 (2662 (1244) against 2395 (238) ng h mL−1, p=0·034). Overall the two modes of administration did not produce bioequivalent pharmacokinetic profiles. Also HS dosing gave significantly higher plasma concentrations of diltiazem in the early morning hours when the incidence of cardiovascular events is higher. If one assumes a strong correlation between plasma concentrations and myocardial protection then HS dosing should be recommended for QD formulation of diltiazem. Clinical studies should be performed to confirm this theoretical pharmacokinetic advantage. 相似文献
33.
目的:在时辰药理学原理指导下,把药物达峰时间与患者的24 h动态血压相结合,从而确定降压药的最佳服用时间,做到个体化给药。方法:将某院2015年1月-2016年6月住院和门诊收治的高血压患者共100例,随机分为干预组和对照组,各50例。干预组中患者根据其服药前动态血压仪测得的峰值前2 h服药,对照组按常规服药时间早餐后服药。在治疗8周后对2组患者血压控制情况进行比较分析,并记录所有与厄贝沙坦相关的不良反应。结果:治疗前2组患者平均血压之间无明显差异,经治疗后,在随访期内其血压水平均较治疗前有显著下降,治疗后干预组较对照组患者在24h平均收缩压、白天平均收缩压、全天收缩压大于140 mmHg的百分率、全天收缩压大于140 mmHg的时间百分率有明显差异(P<0.05),但在24h平均舒张压、白天平均舒张压、夜间平均收缩压、夜间平均舒张压等方面无明显差异(P>0.05)。结论:时辰药理学原理指导下结合降压药的药动学特点制定的给药时间能更平稳地降压,为合理、个体化地使用降压药提供依据。 相似文献
34.
G. Ferrazzini H. Sohl I. Robieux D. Johnson E. Giesbrecht G. Koren 《European journal of clinical pharmacology》1991,41(5):425-427
Summary There is recent evidence that survival is improved when maintenance therapy for acute lymphocytic leukaemia in children is given at night. We have examined the possibility that diurnal variation in methotrexate pharmacokinetics may contribute to this improvement.In 6 children with leukaemia there was a significant fall in methotrexate plasma clearance at night (from 5.6 to 4.7 ml·kg–1·min–1). Renal clearance of methotrexate tended to fall at night and unbound renal clearance fell significantly (from 17.5 to 8.5 ml·min–1·kg–1
P<0.05). Creatinine clearance did not exhibit diurnal variation, whereas there was a significant fall in the non-glomerular clearance of methotrexate (from 14.8 to 6 ml·min–1·kg–1).Since methotrexate is a weak organic acid, its tubular secretion depends on urinary pH. At night urinary pH is more acidic, and this may result in more reabsorption and hence reduced renal clearance. 相似文献
35.
肿瘤时辰治疗的研究与探索 总被引:2,自引:0,他引:2
大量研究表明抗肿瘤化疗药物具有昼夜节律性。按照时辰药理学原理进行肿瘤时辰治疗,对于减少不良反应,增加最大耐受量,提高疗效方面的优越性,已为现代临床研究证实。现综述各类时辰化疗药物的特性,阐明药物化疗的疗效与毒性和昼夜节律有关,同时说明放疗也存在着时辰依赖性。开展肿瘤时辰治疗正日益受到重视。 相似文献
36.
时辰疗法(chronotherapy)是以生理计时系统(circadian timing system,CTS)和时辰药理学(chronopharmacology)为基础发展起来的区别于传统治疗模式的新型疗法。受生理计时系统的控制,肿瘤细胞增殖和代谢有其周期节律性,因此合理利用时辰疗法的原理和方法开展对恶性肿瘤的治疗,可以达到相同剂量下药物毒性降低、高耐受下采用高剂量以提高疗效的目的。本文就时辰疗法的相关概念及其在恶性肿瘤化疗、放疗、中西医结合治疗以及肿瘤免疫相关方面的应用进展进行综述。 相似文献
37.
1. The response of individually caged mice to the lethal actions of allylglycine and strychnine was evaluated in animals previously conditioned on an LD 12:12 (12 h light-12 h darkness) schedule in a controlled environment. 2. These convulsant agents were most toxic at 18.00 hours (during the light phase), and least toxic in the dark phase of the programmed lighting schedule. The relationship is considered of the circadian fluctuations in levels of inhibitory transmitter substances to the time-linked action of convulsant agents. 相似文献
38.
A. Fujimura M. D. K. Ohashi A. Ebihara 《European journal of clinical pharmacology》1992,43(3):299-301
Summary A time-dependent change in the cholesterol-lowering effect of probucol has been evaluated in 20 subjects with elevated cholesterol.
Probucol 500 mg was given once daily at 07.00 h (day trial) or 19.00 h (night trial) for 3 months according to a crossover
design. Fasting blood samples were obtained during the control period and at the end of each treatment period.
Serum concentrations of total and HDL-cholesterol were significantly decreased by both the treatments with probucol [total
cholesterol (mmol · l−1): control 6.58; day trial 5.41; night trial 5.10; HDL-cholesterol (mmol · l−1): control 1.35; day trial 1.06; night trial 0.96]. These parameters were significantly lower in the night trial than in the
day trial.
The data indicate that the cholesterol-lowering effect of probucol varies with its time of administration in subjects with
elevated cholesterol. 相似文献
39.
Peter Potucek Michal Radik Gabriel Doka Eva Kralova Peter Krenek 《Clinical and experimental hypertension (New York, N.Y. : 1993)》2017,39(8):754-763
Chronopharmacological effects of antihypertensives play a role in the outcome of hypertension therapy. However, studies produce contradictory findings when combination of valsartan plus amlodipine (VA) is applied. Here, we hypothesized different efficacy of morning versus evening dosing of VA in spontaneously hypertensive rats (SHR) and the involvement of circadian clock genes Bmal1 and Per2. We tested the therapy outcome in short-term and also long-term settings. SHRs aged between 8 and 10 weeks were treated with 10 mg/kg of valsartan and 4 mg/kg of amlodipine, either in the morning or in the evening with treatment duration 1 or 6 weeks and compared with parallel placebo groups. After short-term treatment, only morning dosing resulted in significant blood pressure (BP) control (measured by tail-cuff method) when compared to placebo, while after long-term treatment, both dosing groups gained similar superior results in BP control against placebo. However, mRNA levels of Bmal1 and Per2 (measured by RT-PCR) exhibited an independent pattern, with similar alterations in left and right ventricle, kidney as well as in aorta predominantly in groups with evening dosing in both, short-term and also long-term settings. This was accompanied by increased cardiac mRNA expression of plasminogen activator inhibitor-1. In summary, morning dosing proved to be advantageous due to earlier onset of antihypertensive action; however, long-term treatment was demonstrated to be effective regardless of administration time. Our findings also suggest that combination of VA may serve as an independent modulator of circadian clock and might influence disease progression beyond the primary BP lowering effect. 相似文献
40.
微生态制剂治疗388例急性腹泻患儿的临床研究 总被引:2,自引:1,他引:1
目的比较多西他赛在不同时间点给药后的血药浓度、疗效以及毒性反应的变化,根据其节律变化选择临床最佳给药时间,获得最佳疗效。方法经病理和细胞学证实的60例III、IV期非小细胞肺癌(NSCLC)患者随机分为3组。多西他赛:A组(n=20)在8∶00 am给药,B组(n=20)在2∶00 pm给药,C组(n=20)在8∶00 pm给药;顺铂在多西他赛给药后第2天给予。多西他赛40 mg.m-2,ivgtt,d1,8;顺铂75 mg.m-2,ivgtt,d1,第21天重复。测定给药后1,10,24 h的血药浓度,并评价经化疗2个周期后的疗效和不良反应。结果3组的疗效和血药浓度在统计学上没有显著性差异,但2:00 pm,8:00 pm给药组的不良反应发生率较高。结论多西他赛治疗NSCLC在8∶00 am给药较为安全有效,可增加病例数做进一步的深入研究。 相似文献