The pharmacokinetics of non-steroidal anti-inflammatory drugs in the elderly

The elderly often suffer from chronic musculoskeletal disease, and non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to control symptoms. The aged have been shown to be particularly at risk of adverse effects from these drugs, of which gastrointestinal irritation and bleeding are both common and potentially serious. Because of this, a comparison of NSAID pharmacokinetics in young and elderly subjects is of particular importance. In general, protein binding tends to decrease with age; volumes of distribution may undergo a small increase; and clearance, especially of renally eliminated drugs, may fall. However, these changes are relatively minor, and the increased propensity of the elderly to suffer adverse reactions to NSAIDs cannot readily be explained on a pharmacokinetic basis.     

Modelling circadian variation in the pharmacokinetics of non-steroidal anti-inflammatory drugs

Summary A one-compartment model with first-order absorption has provided good fits to five sets of indomethacin data and four sets of ketoprofen data taken at different times of day. There was substantial variation in the model parameters with time of administration and most of the features of this variation applied equally to both drugs. From the data examined, the source of variation appears to be mainly in the absorption phase and this was confirmed using a chronokinetic analysis, in which simultaneous fits were obtained with time-variant rate parameters. However, there may also be circadian variation in protein binding.The danger of quoting parameter values for either of these two drugs based on administration at a single time of day has been illustrated, and this may well be true for other drugs.     

Recent findings on the pharmacokinetics of non-steroidal anti-inflammatory drugs in synovial fluid

Synovial fluid concentration is considered to be an important determinant of clinical response to non-steroidal anti-inflammatory drugs (NSAIDs). Trans-synovial transport of these drugs is a process of limited diffusion, governed partly by the pharmacological characteristics of NSAIDs and partly by the properties of the joint and joint space themselves. The studies which report simultaneous pharmacokinetics of NSAIDs in both plasma and synovial fluid compartments are of 2 types: (1) some compare the concurrent concentrations of drugs in plasma and joint fluid after a single administration. These provide pharmacokinetic information: (2) others, which conform more closely to the therapeutic conditions, look at synovial fluid and plasma concentrations after repeated administration of the drug. Recent findings on the pharmacokinetics of NSAIDs in synovial fluid are reviewed. These studies reveal 2 types of NSAIDs, according to their pharmacokinetic behaviour. First, there are NSAIDs with a short or intermediate plasma elimination half-life. These drugs equilibrate rapidly relative to their elimination; their peak synovial fluid concentrations occur later and are lower than those in plasma. Several hours after administration there is crossover of the concentration curves, and beyond this point, concentrations in synovial fluid may exceed those in plasma. During prolonged treatment, the synovial fluid concentrations of these NSAIDs fluctuate to a much lesser extent than plasma concentrations. Secondly, there are NSAIDs with a long plasma elimination half-life; their peak concentration in synovial fluid is also lower and later than that in plasma. At steady-state their concentrations (total and free) in synovial fluid are about half those in plasma. Numerous variables must be taken into account in attempts to correlate synovial fluid NSAIDs concentrations with clinical response, including protein binding and determination of both active metabolites and (eventually) the enantiomers.     

Clinical economics review: gastrointestinal complications of non-steroidal anti-inflammatory drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used symptomatic remedies for rheumatic disorders. Their major side-effects involve the gastrointestinal tract and, while the stomach is often the prime focus of adverse reactions, the whole gut may be involved. A number of strategies have been used to reduce both the incidence of side-effects and their economic consequences. Decreased NSAID use can be achieved both by rational prescribing and by active promotion of other, usually non-pharmacological, methods of controlling symptoms. Prescribing NSAIDs based on their cost assumes all have equal efficacy and side-effects, which is demonstrably untrue. Picking the least toxic NSAID is more logical. Most of the larger studies and meta-analyses available concentrate on older NSAIDs and risk overlooking the advantages of newer preparations which have been shown to be cost beneficial by more comprehensive economic analyses. Misoprostol prophylaxis has been the subject of a number of economic evaluations which, until recently, were based on extrapolations rather than clinical data. There are now good clinical data available which show a small but significant reduction in major side-effects at the expense of an increase in minor but unpleasant ones. Proton pump inhibitors appear to offer the same degree of gastroprotection as misoprostol, with the additional benefit of symptom relief. Economic data regarding the costs and benefits of prophylaxis with proton pump inhibitors are not yet available. There is still a need for a more comprehensive evaluation of the benefits of NSAIDs in different clinical situations to balance against the costs of adverse reactions.     

非甾体类抗炎药致上消化道出血的临床分析

目的探讨非甾体类抗炎药(NSAIDs)致上消化道出血的临床特点。方法对182例上消化道出血患者的临床资料进行回顾性分析,根据出血前1周内是否服用过NSAIDs,将患者分为NSAIDs组(43例)和非NSAIDs组(139例)。对比分析两组患者的临床资料。结果两组比较,NSAIDs组与非NSAIDs组在年龄、溃疡类型等方面差异有统计学意义。结论应加强对NSAIDs相关性上消化道出血临床特点的认识,以减少NSAIDs的不良反应。     

NSAIDs抗炎作用机制研究进展

NSAIDs的抗炎作用机制被认为主要是抑制COX2的活性。NSAIDs还可以抑制COX2的表达,并可通过COX非依赖性的途径产生抗炎作用,包括抑制转录因子NFκB与AP1,作用于蛋白激酶如Erk、p38MAPK、及核糖体S6激酶2等,激活PPARγ及热休克转录因子1,抑制诱导型NO合酶及前列腺素转运等。     

非甾体抗炎药的合理应用

1899年阿司匹林问世开创了人类用合成抗炎药的历史.百余年来,以其为代表相继开发的一大批具有独特药理作用的抗炎药在临床上占有重要治疗地位,成为一日不可或缺的药品.为此临床医师应了解并合理地应用.     

Assessment of topical non-steroidal anti-inflammatory drugs

A new non-invasive technique for assessing the efficacy of topical non-steroidal anti-inflammatory drugs (NSAID) in man is proposed. The NSAID are initially applied to the skin under occlusion before inflammation is induced by a methyl nicotinate solution. The inflammatory response is quantified in terms of cutaneous blood flow by a laser Doppler velocimeter (LDV). The efficacy of NSAID preparations is calculated by comparing the responses of the LDV to the methyl nicotinate challenge on the pretreated and the non-treated skin sites. This protocol has been used to investigate the effect of three different NSAID preparations (indomethacin, niflumic acid, palmitoyl collagenic acid) and the influence of the vehicle on the efficacy of indomethacin. The three preparations tested gave positive results but with different amplitudes in response. The efficacy of indomethacin varied with the vehicle used.     

Effects of non-steroidal anti-inflammatory drugs on the pharmacokinetics and elimination of aciclovir in rats

This study aims to investigate the effect of commonly used non-steroidal anti-inflammatory drugs (NSAIDs) on the pharmacokinetics and the renal elimination of aciclovir in rats. Pharmacokinetic parameters were determined following an intravenous administration of aciclovir (5 mg kg(-1)) to rats in the presence and absence of ketoprofen or naproxen (25 mg kg(-1)). Compared with the control (given aciclovir alone), pre-treatment with ketoprofen or naproxen 30 min before aciclovir administration significantly altered the pharmacokinetics of aciclovir. Renal clearance of aciclovir was reduced by approximately two fold in the presence of ketoprofen or naproxen. Consequently, the systemic exposure (AUC) to aciclovir in the rats pre-treated with ketoprofen or naproxen was significantly (P < 0.05) higher than that from the control group given aciclovir alone. Furthermore, the mean terminal plasma half-life of aciclovir was enhanced by 4-5 fold by pre-treatment with ketoprofen or naproxen. These results suggest that NSAIDs, such as ketoprofen and naproxen, are effective in altering the pharmacokinetics of aciclovir by inhibiting the organic anion transporter-mediated tubular secretion of aciclovir. Therefore, concomitant use of ketoprofen or naproxen with aciclovir should require close monitoring for clinical consequence of potential drug interaction.     

非甾体类抗炎药相关性上消化道出血的临床特点

目的探讨非甾体类抗炎药相关性上消化道出血的临床特点。方法选择因呕血或黑便就诊并行胃镜检查确诊的216例患者,分为NSAIDs组和非NSAIDs组,比较两组患者临床特点、内镜特点及幽门螺杆菌（HP）感染情况。结果结果显示两组患者的性别、出血方式比较差异无显著性（P〉0．05）;而年龄、出血前消化道症状、心血管病史、HP感染及内镜特点两组比较差异有显著性（P〈0．05）。结论非甾体类抗炎药相关性上消化道出血多见于老年人,有心血管病史,以粘膜糜烂及胃溃疡居多,HP感染增加了NSAIDs相关性胃黏膜损害。     

Cardiovascular hazard and non-steroidal anti-inflammatory drugs

Selective inhibitors of cyclooxygenase (COX)-2 depress prostacyclin (PGI(2)) without a concomitant inhibition of platelet COX-1-derived thromboxane (Tx)A(2). Experiments in gene-deleted mice have shown that ablation of the PGI(2) receptor (the IP) predisposes to an exaggerated response to agonists which elevate blood pressure, accelerate atherogenesis and induce thrombosis. Such a class-based effect would be expected to be modulated by the underlying risk of cardiovascular disease in patients, elements of drug exposure, such as dose, duration of action and duration of dosing, and inter-individual variability of drug response. Five placebo-controlled trials of three structurally distinct selective inhibitors of COX-2 have revealed an increased hazard of myocardial infarction and stroke consistent with a mechanism-based class-specific cardiovascular hazard. Sustained inhibition of platelet TxA(2) by aspirin affords cardiovascular benefit, despite concomitant inhibition of PGI(2). Although there is no information from randomized placebo-controlled trials, traditional non-steroidal anti-inflammatory drugs, such as naproxen, dicofenac and ibuprofen, might differ in their effects of cardiovascular biology.     

Cutaneous reactions to non-steroidal anti-inflammatory drugs

We retrospectively reviewed the records of 195 patients with suspected cutaneous reactions from NSAIDs. Two hundred and six different non-steroidal anti-inflammatory drugs (NSAIDs) were suspected of causing cutaneous reactions, and the most frequent suspected causative NSAID was ibuprofen (25.7%). Angioedema and/or urticaria were the most frequent cutaneous reactions (54.4%), and the foremost suspected causative drug for these reactions was ibuprofen. The second most frequently found cutaneous reaction was maculopapular eruption (26.2%), and celecoxib was the most commonly suspected causative NSAID for it. The primary suspected NSAIDs causing fixed drug eruption were in enolic acid group. Furthermore, drug hypersensitivity syndrome was diagnosed in five patients, and Stevens-Johnson syndrome and toxic epidermal necrolysis were detected in five patients.     

结肠直肠癌和非甾类消炎药(英文)

Non-steroidal anti-inflammatory drugs ( NSAIDs) can prevent or reduce the occurrence of colorectal cancers . Anti-carcinogenic properties of NSAIDs have been demonstrated in epidemiological studies of humans and experimental animals. In addition, clinical studies of familial adenomatous polyposis and sporadic adenomas have demonstrated that NSAIDs induce regression of colorectal adenomas and prevent formation of these tumors. NSAIDs thus induce early disruption of the adenoma-carcinoma sequence and may mainly suppress subsequent cancer formation at adenoma stage. The mechanism of the anti-carcinogenic effect of these drugs is not known, but results of most studies support that cyclooxygenase-2 (an inducible isoform of prostaglandin synthetase, COX-2) is a major target of NSAIDs in this effect. Recent immunohistochemical studies have revealed that COX-2 is expressed not in tumor cells but in interstitial cells of colonic adenomas. Accordingly, NSAIDs may exhibit anti-carcinogenic property through the inh     

非甾体抗炎药与麻醉药的相互作用

非甾体抗炎镇痛药(Non-steroidal anti-inflammatory drugs,NSAIDs)主要用于围手术期超前镇痛。本文对NSAIDs与常用的麻醉药如阿片类药、吸入麻醉药、静脉麻醉药和苯二氮艹卓类药物的相互作用加以综述。