Chronopharmacology

The time of day that drugs are given can have a profound effect upon both their pharmacodynamics, i.e. their effectiveness and toxicity, and their pharmacokinetics, i.e. the way they themselves behave in the body. The chronopharmacokinetics of relatively few drugs have been investigated and are mostly those used for the treatment of cancer. We have shown that the toxicity and chronopharmacokinetics of drugs can be altered by pretreatment with steroids or melatonin.     

华蟾酥毒基药理作用及剂型研究进展

华蟾酥毒基（Cinobufagin）是蟾酥中的一种单体,具有多种生物学效应,目前对其功效研究颇多,剂型研究也较多,现对华蟾酥毒基药理作用及制剂研究状况进行简要总结,为制备高效实用的临床药物提供有益线索。     

高眼压缺血-再灌注中脑组织NOS的表达及神经营养因子对其表达的影响

目的 :观察视网膜缺血再灌注损伤过程中脑组织一氧化氮合酶 ( NOS)的变化及神经营养因子对 NOS表达的影响 ,探讨 NOS在脑组织不同部位的改变及可能作用机制 ,进而为临床实践提供依据。方法 :建立眼缺血再灌注损伤动物模型 ,分为对照组、实验组。实验 组为缺血组 ( I组 ) ,实验 组为缺血 2 h+再灌注组 ( I/R组 ) ,实验 组在缺血再灌注前于右侧侧脑室注射神经营养因子 (神经营养因子 + I/R组 )。采用 HE常规染色切片光镜下观察大鼠高眼压脑外侧膝状体、嘴侧丘、视皮质结构神经细胞变化 ,采用免疫组织化学染色分别测定各组大鼠中脑组织以上三个部位 NOS的变化。结果 :1脑组织不同部位中 NOS在对照组、缺血组、缺血再灌注组间无统计学差异。 2在再灌注 1 d组脑组织不同部位的NOS与缺血再灌注组有显著性统计学差异 ,其中在外侧膝状体中有明显改变。 3在再灌注1 d组与再灌注 2 d组间两者存在统计学差异。 4在再灌注后 5 d组与 2 d组间 NOS无统计学差异。 5在注射神经营养因子的实验 组 ,脑组织中不同部位的 NOS与对照组无统计学差异。结论 :NOS在脑外侧膝状体、嘴侧丘、视皮质参与损伤的作用。在外侧膝状体中 NOS的变化在中枢调节作用中起着中介作用 ,NOS可能参与引起脑组织改变。神经营养因子能明显减轻?     

Use of psychotropic drugs in 0 to 5 years old children in Aquitaine (France): prevalence and associated factors

PURPOSE: To describe the use of psychotropic drugs in children aged 0-5 years, in the Aquitaine region of South-west France and identify associated socio-demographic, familial and medical factors. METHODS: Data used in this study come from the regional drug claims database of the National Health Insurance System of Aquitaine and from postal self-questionnaires sent to parents and prescribing physicians. RESULTS: In Aquitaine, psychotropic drugs were redeemed at least once in 2002 for 3.2% of young children. Hydroxyzine, niaprazide or diazepam were claimed at least once by 2.7% of children registered in the database. Prescribers were mostly general practitioners (76.7%) and pediatricians (20.1%). Psychotropic claims were more frequent in children having the highest number of medical consultations in 2002 (more than 7: odds ratio (OR) = 1.5 [95% confidence interval (CI): 1.3-1.7]) or of drug deliveries (7-15 deliveries: OR = 1.8 [95%CI: 1.6-2.1]; more than 15 deliveries: OR = 3.2 [95%CI: 2.7-3.9]). Psychotropic claim frequency increased with age. No association of psychotropic use with parental psychotropic use, socio-professional category and familial situation was found. CONCLUSIONS: Psychotropic delivery prevalence in Aquitaine in young children was below 5% in 2002. It notably concerned drugs of which the use is not devoid of toxicity because of anticholinergic properties.     

Effects of pharmaceuticals and other active chemicals at biological targets: mechanisms,interactions, and integration into PB-PK/PD models

Biologically active molecules, that is pharmaceuticals and other chemical substances, exert their therapeutic and/or toxic effects by complex interactions with their biological targets/active sites. This review discusses the factors and processes governing the kinetics and effects of active molecules at their cellular targets, the chain of events leading to clinical effects, and the crosstalk between regulatory pathways controlling these processes. Special attention is given to the discussion of effects of a single drug or other chemical on multiple targets, to the interaction of multiple ligands with a single target/receptor and the effects of single ligand–target complexes on multiple signal transduction pathways, and to the control of physiological functions, such as regulation of blood glucose levels, by numerous primary mechanisms acting on different cellular targets. Physiologically based-pharmacokinetic/pharmacodynamic (PB-PK/PD) models are of great value for the design of active principles by the pharmaceutical industry and for the optimization and individualization of patient therapy. Experimental results from in vitro and in vivo studies can be used for building such models. On the other hand, properly designed models and simulation can contribute to a better design of experiments. Much of what is presented in this article applies equally well to drugs and other chemicals. Unless specified otherwise, reference to drugs applies also to other chemicals. This review is based on an expert meeting organized by COST Action B25 held in Eilat, Israel, on 14 – 15 February 2008. The authors have prepared this article to reflect the presentations and discussions at that meeting.     

Metformin‐associated risk of acute dialysis in patients with type 2 diabetes: A nationwide cohort study

Recent guidelines governing anti‐diabetic medications increasingly advocate metformin as first‐line therapy in all patients with type 2 diabetes. However, metformin could be associated with increased risk of acute kidney injury (AKI), acute dialysis and lactate acidosis in marginal patients. In a retrospective nationwide cohort study, a total of 168 443 drug‐naïve patients with type 2 diabetes ≥50 years, initiating treatment with either metformin or sulphonyl in Denmark between 2000 and 2012 were included in this study (70.7% initiated treatment with metformin); calculation of 1‐year risk of acute dialysis was based on g‐standardization of cause‐specific Cox regression models for acute dialysis, end‐stage renal disease and death. One‐year risks of acute dialysis were 92.4 per 100 000 (95% CI, 67.1‐121.3) and 142.7 per 100 000 (95% CI, 118.3‐168.0) for sulphonylurea and metformin, respectively. The metformin‐associated 1‐year risk of acute dialysis was increased by 50.3 per 100 000 (95% CI, 7.9‐88.6), corresponding to a risk ratio of 1.53 (95% CI, 1.06‐2.23), and a number needed to harm of 1988, thus providing evidence of potential concerns pertaining to the increasing use of metformin.     

冰片药理作用的研究进展

综述冰片的药理作用,药物动力学及毒理学的研究概况。冰片能显著促进治疗中枢神经系统疾病药物的吸收,提高治疗药物脑组织中的浓度,对中枢神经系统疾病的治疗具有一定的研究开发价值。