治头痛药物ibuprofen或可有效治疗结肠癌

美国的科学家5月20日表示,一种廉价的治头痛药ibuprofen不但有助预防结肠癌,而且还可能是较有效的疗法。研究人员表示,在每日服用小剂量的ibuprofen之後,罹患癌症的老鼠身上肿瘤变小了,死于结肠癌的几率也降低。研究者让实验室中患结肠癌的老鼠连续21天只服用ibuprofen,或者同时服用ibuprofen与辉瑞(Pfizer)的标准结肠癌药物irinotecan(商品名称为Camptosar)或5-fluororacil。到了第50天,没有服药的老鼠全数死亡。但只服用ibuprofen的老鼠死亡率为20%,仅使用Camptosar的老鼠也有20%死亡,而同时服用ibuprofen和Camptosar的老鼠仅有10%死亡…     

Solubilization of ibuprofen with β-cyclodextrin derivatives: energetic and structural studies

The aim of this work was to investigate the complexation of ibuprofen as model drug with various β-cyclodextrins (native β-cyclodextrin, hydroxypropyl-β-cyclodextrin with two different molar degrees of substitution, and methyl-β-cyclodextrin). Solutions of the commercially available β-cyclodextrins were prepared in phosphate buffer (73mM). The pH value was adjusted to 7.4 and the solutions were isotonized with NaCl. A solution of ibuprofen was prepared in the same way. A thermal activity monitor was used for isothermal titration calorimetry (ITC). (1)H NMR analysis was employed to investigate the structures of the complexes. ITC analysis showed that each type of β-cyclodextrin had its characteristic values of both enthalpy and mass equilibrium constant for the complexation processes with the drug molecules. (1)H NMR spectroscopy of the complexes showed through significant differences in chemical shifts that the physical interaction between the cyclodextrins and ibuprofen molecules were also different, probably due to different three-dimensional arrangements of ibuprofen in the cyclodextrin cavity, induced by the different substituents bonded to the glucose rings. These differences were connected to the thermodynamic parameters of the complexes.     

Over‐the‐counter ibuprofen: how and why is it used?

Objectives — To pilot an over‐the‐counter (OTC) medicine pharmacovigilance project, using ibuprofen as a model. Method — All users of any tablet or capsule form of ibuprofen (excluding compound products) purchased from 61 participating community pharmacies, aged ≥18 years and able to give informed consent, were eligible to join the study. A postal questionnaire one week after the index purchase monitored the follow‐up rate, drug usage, past medical history, concurrent medication, symptoms and health service utilisation. Setting — Primary care: community pharmacies in Grampian, Scotland. Key findings — A total of 443/544 (81 per cent) questionnaires were completed. The recommended daily dose of OTC ibuprofen (1,200mg) was exceeded by 35 customers (8 per cent) on at least one day and the recommended maximum daily dose that can be prescribed by a physician (2,400mg) was exceeded on five occasions. During the seven days after the index purchase, ibuprofen was used by 15 customers (4 per cent) with an active or past history of peptic ulcer, and 30 (7 per cent) with an active or past history of asthma. Thirty‐eight per cent had purchased ibuprofen for a chronic condition and 32 per cent were still taking it at the end of the initial seven‐day period. Twenty‐eight of 412 customers (7 per cent) sought advice during the seven‐day period about at least one symptom: 13 consulted their general practitioner, 12 consulted a pharmacist, two consulted both their GP and a pharmacist, and one consulted a hospital doctor. Some of these consultations (23/28, 82 per cent) might have related to an adverse reaction to ibuprofen: 11 customers (3 per cent) consulted about lower abdominal symptoms, nine about gastric symptoms and three about wheeziness. Conclusions — This pilot study identifies instances of contraindicated and excessive use of OTC ibuprofen, indicating a need for pharmacovigilance studies of OTC medicines; it also demonstrates the feasibility of a major study.     

Does non-steroidal anti-inflammatory (NSAID) ibuprofen induce antioxidant stress and endocrine disruption in mussel Mytilus galloprovincialis?

Ibuprofen (IBU) is one of the most sold over-the-counter non-steroidal anti-inflammatory drugs (NSAID) and widely detected in the aquatic ecosystems. Nevertheless, the information regarding IBU effects in biota is still sparse. The goal of this study was to assess IBU potential effect as oxidative stress and endocrine disruption inducer in mussel Mytilus galloprovincialis applying a battery of biomarkers. Over two weeks of exposure to IBU (250 ngL(-1)), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), phase II glutathione S-transferase (GST) activities and lipid peroxidation (LPO) levels were determined in the digestive gland and alkali-labile phosphates (ALP) were carried out in sex-differentiated mussels' gonads. The results confirm a transitory induction of antioxidant activities responses concomitant to lipid peroxide formation outline and an increase of ALP levels over time, particularly in exposed males which may lead to mussels' reproductive fitness impairment highlighting a higher impact of IBU as an endocrine disruptor than as a short-term reactive oxygen species (ROS)-generator.     

How suitable is the measurement of take-off forces for detection of sticking during direct compression of various ibuprofen tablet formulations?

Sticking of tablet formulations to punch surfaces is one of the most common problems observed during tablet manufacture. An inline method proposed for detection of sticking during compression is the measurement of take-off forces, which occur when tablets are detached from the lower punch surface. It has been postulated that the tablet take-off force is a direct indicator of the sticking tendency of a tablet formulation. In the present study, the take-off forces measured during direct compression of sticking ibuprofen tablet formulations were evaluated and compared to the sticking extent of these tablets quantified by HPLC analysis of ibuprofen. As expected, sticking to the lower punch was increased with an increase of the ibuprofen content in the investigated tablet formulations. However, data obtained from take-off force measurements did not correlate with the quantified amount of sticking. Although pronounced sticking was observed, the measured tablet take-off forces remained low even at high drug contents. These results indicate that the tablet take-off force is not a direct indicator of the sticking tendency of ibuprofen tablet formulations. It is suggested that the evaluation of take-off force data requires a differentiated approach. A new interpretation of take-off force data is presented in this paper.     

A polyexponential deconvolution method. Evaluation of the “gastrointestinal bioavailability” and meanin vivo dissolution time of some ibuprofen dosage forms

A new deconvolution algorithm (DCON) suitable for pharmacokinetic applications is presented. It requires that both the impulse and input responses, typically systemic drug levels, be well described by polyexponential equations. DCON has a wider range of applications than an earlier method (DECONV) from which it is derived. A FORTRAN program is provided, making implementation of the technique a simple matter. DCON is demonstrated to evaluate the GI bioavailability, defined as the rate and the extent of gastrointestinal drug release, of various ibuprofen dosage forms. The GI drug release kinetics exemplifies a pharmacokinetic system which cannot be evaluated using the previous deconvolution algorithm (DECONV) because of an initial zero drug level response. This limitation is not found in DCON. It is also demonstrated how the mean in vivo dissolution time MDT can be evaluated by deconvolution.     

Effects of dexamethasone and ibuprofen on LPS-induced gene expresion of TNF_ α,IL-1β,and MIP-1α in rat lung

研究地塞米松（Ｄｅｘ）和布洛芬（Ｉｂｕ）对脂多糖（ＬＰＳ）诱导的大鼠肺ＴＮＦα、ＩＬ-１β和ＭＩＰ-１α基因表达的影响．方法：荧光法测定肺中伊文斯蓝含量，Ｓｌｏｔｂｌｏｔ对细胞因子ｍＲＮＡ表达相对定量．结果：腹腔注射ＬＰＳ导致大鼠肺中ＴＮＦα、ＩＬ-１β和ＭＩＰ-１αｍＲＮＡ表达明显增加，与ＬＰＳ剂量有依赖关系，峰值分别在２，６，１２小时．在ＬＰＳ前１小时给药，Ｄｅｘ５０ｍｇ·ｋｇ－１和Ｉｂｕ９０ｍｇ·ｋｇ－１均明显降低肺中伊文斯蓝含量，同时ＴＮＦα、ＩＬ-１β和ＭＩＰ-１αｍＲＮＡ表达量亦明显减少．结论：ＬＰＳ诱导大鼠肺中ＴＮＦα、ＩＬ-１β和ＭＩＰ-１α基因表达，Ｄｅｘ和Ｉｂｕ通过抑制细胞因子表达而减轻肺损伤．     

A comparison of the effects of etodolac and ibuprofen on renal haemodynamics, tubular function, renin, vasopressin and urinary excretion of albumin and α-glutathione-S-transferase in healthy subjects: a placebo-controlled cross-over study

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are known to be potentially nephrotoxic agents. NSAIDs inhibit the enzyme cyclo-oxygenase and thereby block the prostagladin synthesis in the kidneys. Cyclo-oxygenase exists in two isoforms (COX-1 and COX-2). It has been proposed that NSAIDs with preferential COX-2 selectivity have fewer renal side effects than drugs with preferential COX-1 selectivity. Etodolac is a relative selective inhibitor of COX-2, while ibuprofen has a higher potency against COX-1 than COX-2. Objective: In this study, we compared the effects of etodolac and ibuprofen on renal function, plasma renin, plasma arginine vasopressin and the urinary excretion of albumin and α-glutathione-S-transferase (α-GST). Methods: In a randomised, double-blind, three-way crossover study with placebo, we compared the effects of 2 weeks of treatment with ibuprofen and etodolac on renal haemodynamics [glomerular filtration rate (GFR), renal plasma flow (RPF) and filtration fraction (FF)], tubular function and plasma concentrations of the hormones renin (PRC) and arginine vasopressin (AVP) in 18 healthy subjects. In addition, we examined the effects on the urinary excretion of albumin and α-GST as markers of renal injury. Results: No differences were found between the three treatments, placebo, ibuprofen and etodolac, in the effects on GFR, RPF, FF, free water clearance, urinary output or fractional excretion of potassium and sodium. However, ibuprofen, in contrast to etodolac, caused a significant decrease in both lithium clearance (−16% versus placebo) and the fractional excretion of lithium (−17% versus placebo), suggesting an increase in the re-absorption in the proximal tubuli. PRC was reduced significantly by ibuprofen (−32% versus placebo) but not etodolac. None of the drugs changed AVP. Fourteen days of treatment with ibuprofen caused a significant decrease (−47% versus placebo) in the urinary excretion of α-GST, while no changes were seen after etodolac. None of the drugs changed the urinary excretion of albumin. Conclusion: In conclusion, a 14-day administration of etodolac or ibuprofen in therapeutic doses did not affect the renal haemodynamics, the net excretion of electrolytes or the urinary excretion of albumin in healthy subjects. However, ibuprofen, in contrast to etodolac, caused a reduction in PRC, suggesting that COX-1 is involved in basal renin release in humans. Furthermore, ibuprofen decreased lithium excretion suggesting that COX-1 is involved in the re-absorption of sodium and/or water in the proximal tubuli. The reduction in the urinary excretion of α-GST by ibuprofen may be caused by an inhibition of the detoxification enzyme by ibuprofen. Overall the study indicates that only small differences in the effects of the two drugs on renal function in healthy subjects exist during a treatment period of 2 weeks. Received: 10 November 1999 / Accepted: 21 April 2000