小剂量左氨氯地平、替米沙坦及氢氯噻嗪同时或不同时给药降压及逆转非杓型高血压的临床分析

目的探讨小剂量左氨氯地平、替米沙坦及氢氯噻嗪同时或不同时给药降压及逆转非杓型血压的效果。方法选择300例收缩压（SBP）〈180mmHg,舒张压（DBP）91～109mmHg,年龄〉45岁的非杓型高血压患者,随机分为两组,I组（不同时给药组）晨服替米沙坦40mg和氢氯噻嗪10mg,晚服左氨氯地平2．5mg;Ⅱ组（同时给药组）以上3种药物均晨服,所有病例治疗前及治疗8周后进行动态血压监测。结果（1）治疗8周后,I组和Ⅱ组的24hSBP／DBP分别降低14．92／9．96和15．04／10．66mmHg,日间SBP／DBP分别降低13．90／10．60和16．06／11．70mmHg,均较治疗前明显降低（P〈0．01）;两组24h和日间SBP／DBP治疗后差异无统计学意义（P〉0．05）。（2）I组夜间SBP／DBP降低25．44／19．48mmHg,与治疗前相比差异非常显著（P〈0．01）。（3）Ⅱ组夜间SBP／DBP降低17．68／14．76mmHg,与治疗前差异也有统计学意义（P〈0．05）。（4）治疗后夜间SBP／DBP降幅I组较Ⅱ组差异更明显（P〈0．01）。（5）I组逆转率为88．16％,Ⅱ组为55．41％,两组比较差异有统计学意义（P〈0．01）。结论小剂量左氨氯地平、替米沙坦及氢氯噻嗪两种服药方法均能有效地控制24h血压和日间血压,而不同时给药能更好地逆转非杓型高血压。     

动态血压评价不同时间服用氨氯地平的降压效应

目的：研究服药时间对氨氯地平降压效应的影响。方法：采用随机、开放、自身对照的研究方法。高血压患者经二周安慰剂导入期,服安慰剂末诊室血压在９５￣１１５ｍｍＨｇ者入选,随机于７：００或２１：００予５ｍｇ氨氯地平治疗,二周后降压不满意者加至１０ｍｇ,服用氨氯地平六周后,交换服药时间再服六周。服安慰剂末、早晨给药六周、睡前给药六周后分别行动态血压监测,分析其Ｔ／Ｐ、收缩压峰值,舒张压峰值,夜间收缩压和舒张     

Effect of administration of low‐dose irbesartan and hydrochlorothiazide combined with levamlodipine at different times on the circadian rhythm of blood pressure and the levels of MMPs and TIMPs in non‐dipper patients with grade 1 and 2 hypertension

This study aimed to probe the effects of low‐dose irbesartan and hydrochlorothiazide in combination with levamlodipine at different times on the circadian rhythm of blood pressure, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) levels in patients with non‐dipper hypertension (NDH). In this prospective randomized controlled trial, 124 patients with NDH who visited our hospital between August 2018 and July 2021 were enrolled and divided into morning (62 patients) and night (62 patients) medication groups according to the random number table method. All patients received low‐dose irbesartan and hydrochlorothiazide combined with levamlodipine, with the morning medication group taking the medication between 7:00 and 10:00 and the night medication group taking the medication between 19:00 and 22:00 for 24 weeks. The effect of antihypertensive medication in both groups was measured, and changes in ambulatory blood pressure, blood pressure circadian rhythm, left ventricular structure, vascular endothelial function, MMPs, and TIMPs levels were observed before treatment initiation and after 24 weeks of treatment in both groups. The percentage of the dipper type was higher in the night medication group than in the morning medication group, while the percentage of the non‐dipper type was lower in the morning medication group (p < .05). Low‐dose irbesartan and hydrochlorothiazide combined with levamlodipine at different times can effectively treat NDH, but bedtime dosing is more beneficial in reducing nocturnal blood pressure, reversing NDH, improving the circadian rhythm of blood pressure, left ventricular structure, regulating vascular endothelial function, increasing MMPs levels, and reducing TIMP levels.     

An Electrically Modulated Drug Delivery Device. II. Effect of Ionic Strength,Drug Concentration,and Temperature

The effects of various physicochemical parameters on the changes in drug delivery rate produced by an electrophoretic current are examined using a model system. It was shown that ionic strength has an inverse relationship with the change in delivery rate produced by a given current. Small changes in pH were measured during electrophoresis experiments which were considered to be insignificant. Drug reservoir concentration selection is critical in the design of an electrophoretic device and is based on achieving a balance between providing a suitable reservoir and allowing adequate electrophoretic control. Electrophoretic control is affected by temperature in a manner which can be predicted using the Arrhenius relationship. The low power requirements of the model system demonstrate the feasibility of using the principle of electrophoresis to control drug delivery rates in a therapeutic system.     

Circadian changes in the bioavailability and effects of indomethacin in healthy subjects

Summary Nine subjects, 19 to 29 years old (2 females) synchronized with activity from 07.00 to 00.00 received a single daily oral dose (100 mg) of indomethacin at fixed hours: 07.00, 11.00, 15.00, 19.00 and 23.00, in random order and at weekly intervals. 1) Chronopharmacokinetics: Venous blood (sampled at: 0, 0.33, 0.67, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0 and 10.0 h post ingestion) was used for plasma drug determination. Circadian changes in peak height, time to peak, area under the concentration-time curve and the disappearance rate were used to characterize indomethacin chronopharmacokinetics. A circadian rhythm of both peak height and time to peak was validated. An evening ingestion led to smallest peak height and longest time to peak. 2) Circadian changes in a set of effects: Eleven physiologic variables were investigated (post absorption) at t=2 h. Circadian rhythms were detected: i) on control day and ii) with evening ingestion for ten of the eleven variables indicating that the subjects' temporal structure did not become altered by an evening ingestion, whereas it did become so by morning ones. Transient changes (n minutes post absorption) measured as T₂₄₀ min post absorption/T_{control day, same clock hour} ratio were also circadian rhythmic for most variables. Again, evening ingestion appeared least disturbing.     

时间生物学在肿瘤学的研究进展

近年时间生物学在基础实验研究中取得飞速发展(包括近日钟基因分子基础、肿瘤细胞近日节律等),带动了时间治疗学的发展,为提高当前肿瘤治疗水平带来极大希望。本文简要介绍肿瘤时间治疗学的临床应用现状。     

基于时辰治疗学的给药技术研究进展

随着时间生物学、时辰药理学及时辰治疗学的不断进步,传统的给药模式已不能满足人体-疾病-药物之间的时效关系,临床需要能依据疾病特点定时释药的符合时辰节律的药物传递系统,而时辰递药系统的发展瓶颈主要在于相应给药技术的应用。本文分别从口服与非口服两方面介绍了现有的时辰给药技术,并对时辰给药系统的发展前景及其局限性进行了客观评价。     

拉西地平的时间药理学对老年非杓型高血压患者的治疗作用

目的探讨不同时间服用钙拮抗剂拉西地平对老年非杓型高血压患者血压的影响。方法筛选出未使用二氢吡啶类钙拮抗剂≥4周的老年非杓型高血压患者66例,随机分为拉西地平晨起服药组(32例)和晚上服药组(34例),4 mg/d,共治疗48周。患者治疗前后分别进行24 h动态血压监测的检查。结果晨起服药组患者昼间收缩压迭标率为46.9%,晚上服药组为38.2%,两组比较差异无统计学意义(P>0.05)。晨起服药组患者夜间收缩压达标率为28.1%,晚上服药组为67.6%,两组比较差异有统计学意义(P<0.01)。晨起服药组患者由非杓型纠正为杓型18.8%,晚上服药组47.1%,两组比较差异有统计学意义(P<0.01)。结论对于非杓型老年高血压患者,拉西地平可以较好地纠正夜间的高负荷血压,提高夜间血压达标率。     

时辰医学与中药的时间治疗方法

时辰医学是中医学的一个分支学科,其中的时辰治疗学是根据时辰节律来选择最佳的用药时间以达到安全用药的目的,时辰医学发展经历了萌芽期、形成期、发展期及提高期,并于20世纪70年代由我国学者首次提出中医时辰医学的概念.时辰医学早期应用体现在择时服药的治疗手段上,此法与现代的时间治疗学相似.时辰治疗学包含了因时制宜、择时用药.中药应用则体现在一是开提外透的药物,宜于午前服用;沉降下行药物宜于午后服用.二是温和补气的药物,宜于清晨至午前服用;滋阴养血的药物,宜于入夜服用.三是祛除阳分,气分之邪的药物,宜于清晨服用;清阴分伏火的药物,宜于入夜服之.     

大鼠血糖的昼夜节律及格列吡嗪对糖尿病大鼠的时间治疗学

目的：研究正常大鼠及糖尿病大鼠血糖变化的昼夜节律；对格列吡嗪治疗糖尿病大鼠的药效进行时间治疗学研究，以探索合适的用药时间。方法：测定正常大鼠及糖尿病大鼠6：00、12：00、18：00、0：00的血糖，分析其昼夜节律性；分别于9：00或21：00用格列吡嗪灌胃糖尿病大鼠，比较不同时间点治疗后各组的平均血糖及血糖波动情况。结果：正常大鼠血糖变化呈明显昼夜节律性，糖尿病大鼠血糖变化无明显昼夜节律；9：00用格列吡嗪治疗糖尿病大鼠时，其平均血糖及血糖波动值均小于21：00用药组。结论：正常大鼠血糖变化有昼夜节律性；用格列吡嗪治疗糖尿病大鼠，早晨用药疗效优于晚上用药。