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991.
Jeany M Rademaker-Lakhai Desiree van den Bongard Dick Pluim Jos H Beijnen Jan H M Schellens 《Clinical cancer research》2004,10(11):3717-3727
PURPOSE: NAMI-A [H(2)Im[trans-RuCl(4)(DMSO)HIm] or imidazolium-trans-DMSO-imidazole-tetrachlororuthenate] is a novel ruthenium-containing compound that has demonstrated antimetastatic activity in preclinical studies. This Phase I study was designed to determine the maximum-tolerated dose (MTD), profile of adverse events, and dose-limiting toxicity of NAMI-A in patients with solid tumors. Furthermore, the ruthenium pharmacokinetics (PK) after NAMI-A administration and preliminary antitumor activity were evaluated. PATIENTS AND METHODS: Adult patients with solid tumors received NAMI-A as an i.v. infusion over 3 h daily for 5 days every 3 weeks. PK of total and unbound ruthenium was determined during the first and second treatment using noncompartmental pharmacokinetic analysis. The total accumulation of ruthenium in WBCs was also quantified. RESULTS: Twenty-four patients were treated at 12 dose levels (2.4-500 mg/m(2)/day). At 400 mg/m(2)/day, blisters developed on the hands, fingers, and toes. At 500 mg/m(2)/day, blisters persisted from weeks to months and slowly regressed. Although no formal common toxicity criteria (CTC) grade 3 developed, painful blister formation was considered dose limiting. Because the first signs developed at 400 mg/m(2)/day, the advised dose for further testing of NAMI-A was determined to be 300 mg/m(2)/day on this schedule. PK analysis revealed a linear relationship between dose and area under the concentration-time curve (AUC) of total and unbound ruthenium (R(2) = 0.75 and 0.96, respectively) over the whole dose range. Plasma clearance of total ruthenium was 0.17 +/- 0.09 liter/h, and terminal half-life was 50 +/- 19 h. The volume of distribution at steady state of total ruthenium was 10.1 +/- 2.8 liters. The accumulation of ruthenium in WBC was not directly proportional to the increasing total exposure to ruthenium. One patient with pretreated and progressive nonsmall cell lung cancer had stable disease for 21 weeks. CONCLUSION: NAMI-A can be administered safely as a 3-h i.v. infusion at a dose of 300 mg/m(2)/day for 5 days, every 3 weeks. 相似文献
992.
993.
Evaluation of a non-breath-hold MR cholangiography technique 总被引:15,自引:0,他引:15
Macaulay SE; Schulte SJ; Sekijima JH; Obregon RG; Simon HE; Rohrmann CA Jr; Freeny PC; Schmiedl UP 《Radiology》1995,196(1):227
994.
International Journal of Clinical Pharmacy - 相似文献
995.
996.
Focal appendicitis confined to the tip: diagnosis at US 总被引:5,自引:1,他引:4
997.
甘草叶中酚酸和黄酮甙类成分的分离鉴定 总被引:5,自引:0,他引:5
自甘草(Glycyrrhiza uralensis Fiseh)的干燥叶中分离到7个甙类成分,经化学方法和光谱分析确定结构为原儿茶酸-1-O-β-D-呋喃木糖酯甙(1-O-protocatechuyl-β-D-xylopyranose,Ⅰ)、洋芹素-6,8-C-二葡萄糖甙(vicenin-2,Ⅱ)、异鼠李素-3-O-芸香糖甙(narcissin,Ⅲ)、山柰酚-3-O-芸香糖甙(nicotiflorin,Ⅳ)、山柰酚-3-O-β-D-葡萄糖甙(astragalin,Ⅴ)、槲皮素-3-O-芸香糖甙(rutin,Ⅵ)和槲皮素-3-O-β-D-葡萄糖甙(isoquercitrin,Ⅶ)。其中,Ⅰ是新化合物,命名为乌拉尔新甙(uralenneoside);Ⅲ在本属植物中为首次报道;Ⅲ~Ⅶ在乌拉尔甘草中首次分得。Ⅱ~Ⅶ都是已知活性成分。 相似文献
998.
P-R-A-C-T-I-C-A-L: a step-by-step model for conducting the consultation in general practice 总被引:2,自引:1,他引:1
BACKGROUND: It has been shown that when patients are unable to express all
their major concerns, they are less likely to follow the physician's
prescribed treatment plan and they are less satisfied. On the other hand,
the GP has a limited amount of time to elicit all the appropriate
information and must ask certain questions about the biological aspects of
the illness in order to carry out her professional responsibilities. By
acting in a patient-centred way, first enabling the patient to express
himself, the GP can make maximum use of patients' ability for problem
formulation and solution. METHODS: We describe a model, for which the
mnemonic, P-R-A-C-T-I-C-A-L, will help the practitioner to remember its
nine steps. The model uses a chronological succession of strategies during
the consultation that balances the voices of medicine and the lifeworld. In
overview, the GP takes the patient, step by step, first through an
exploration and clarification of his views of the illness, then expands the
problem by further examination (e.g. the physical examination), a
negotiation about the final model of the illness that includes both
diagnosis and management, a discussion of the treatment plan, and finally a
moment of reflection to prepare for the next visit.
相似文献
999.
SUMMARY A case of pseudoephedrine toxicity is reported in a man with chronic renal failure. The effects of renal impairment on the metabolism of pseudoephedrine are discussed and the implications of the widespread availability of the drug in proprietary cold remedies are highlighted. 相似文献
1000.
经典恒温法和多元线性模型预测药物稳定性的空间解析 总被引:7,自引:0,他引:7
应用三维坐标系,以图示方式解析药物稳定性预测法中经典恒温法数据处理的复杂性,提出一个简便的药物稳定性预测方法多元线性模型。此模型是以药物的浓度函数ln[f(c0)-f(c)]和绝对温度的倒数1/T为变量,对时间的对数ln(t)进行多元线性回归,以此计算药物的活化能和室温贮存期。结果表明:多元线性模型可以简化数据处理,明显减少实验工作量和误差。 相似文献