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101.
Development of a LC method for pharmaceutical quality control of the antimetastatic ruthenium complex NAMI-A 总被引:1,自引:0,他引:1
Bouma M Nuijen B Jansen MT Sava G Picotti F Flaibani A Bult A Beijnen JH 《Journal of pharmaceutical and biomedical analysis》2003,31(2):215-228
Imidazolium trans-tetrachloro(dimethylsulfoxide)imidazoleruthenium(III) (NAMI-A) is a novel ruthenium complex with selective activity against metastases currently in Phase I clinical trials in the Netherlands. Pharmaceutical quality control of NAMI-A drug substance and lyophilized product warranted the development of an assay for determination and quantification of NAMI-A and degradation products. A high performance liquid chromatography (HPLC) method was developed, consisting of a C18 column with 0.50 mM sodium dodecylsulfate in 3% methanol at pH 2.5 (acidified using trifluoromethanesulfonic acid) as the mobile phase and UV-detection at 358 nm. The HPLC method was proven to be linear, accurate and precise. Stress testing showed that degradation products were separated from the parent compound. By combining results of nuclear magnetic resonance (NMR) and HPLC experiments, one degradation product was identified as the mono-hydroxy species of NAMI-A. HPLC analysis with off-line detection of the eluate with flameless atomic absorption spectrometry (F-AAS) showed that under most conditions, all ruthenium-containing compounds show a peak in the HPLC chromatogram and that all ruthenium applied to the column is recovered quantitatively. For completely degraded solutions of NAMI-A some ruthenium is retained on the column. Suitability of the HPLC method for the pharmaceutical quality control of NAMI-A lyophilized product was demonstrated. 相似文献
102.
Bongard HJ Pluim D Waardenburg RC Ravic M Beijnen JH Schellens JH 《Anti-cancer drugs》2003,14(6):405-410
E7070 is a novel sulfonamide anticancer agent that arrests the G(1)/S phase of the cell cycle. Preclinical and phase I studies have demonstrated non-linear pharmacokinetics (PK) of the drug. A population PK analysis revealed that the human plasma concentration-time data were best described by a three-compartment model with non-linear distribution. We have studied the in vitro interaction of 14C-radiolabeled E7070 with red blood cells (RBC) and its binding to plasma proteins in the concentration range where non-linearity in disposition was observed in humans to get more insight into the behavior of the drug. After the addition of E7070 to whole blood at 37 degrees C, the drug is taken up or binds to RBC in a concentration-dependent manner. The addition of sodium azide, however, did not result in a decrease of drug uptake by RBC, indicating passive diffusion processes. A non-linear increase in drug uptake was observed at incubation concentrations above 4 microg/ml E7070 in whole blood. This non-linearity was confirmed by lower partition coefficients between RBC and plasma at higher incubation concentrations (from 2.37 at 4 microg/ml to 0.31 at 200 microg/ml). The plasma protein binding of E7070 was high (98-99%) and linear in the concentration range studied (20-200 microg/ml). In conclusion, E7070 in whole blood is preferentially bound to RBC and exhibits high plasma protein binding. The non-linear distribution of E7070 in humans can be caused, in part at least, by saturable binding of E7070 to RBC. 相似文献
103.
de Jonge ME Mathôt RA van Dam SM Rodenhuis S Beijnen JH 《Therapeutic drug monitoring》2003,25(3):261-263
Central venous access catheters are commonly used in clinical oncology. The double lumen variant is applied in pharmacokinetic studies for simultaneous administration and blood sampling when frequent blood collections are necessary. Occlusion of one lumen, a common complication, necessitates the investigator perform blood sampling through the administration lumen after interrupting the infusion. Plasma concentrations measured in this sample can be influenced by sorption of the previously infused compound to the catheter lumen. In this study, the quality of cyclophosphamide, thiotepa, and carboplatin plasma concentrations is investigated when sampling is performed through the administration lumen. 相似文献
104.
105.
Case series of acute hepatitis in a non-selected group of HIV-infected patients on nevirapine-containing antiretroviral treatment 总被引:1,自引:0,他引:1
de Maat MM ter Heine R van Gorp EC Mulder JW Mairuhu AT Beijnen JH 《AIDS (London, England)》2003,17(15):2209-2214
OBJECTIVE: To evaluate the characteristics of patients who developed acute clinical hepatitis in an unselected outpatient population. METHODS: Patients who started a nevirapine-containing regimen in the period January 1999-February 2001 and presented with clinical symptoms in accordance with increased transaminase values within 12 weeks of initiation of nevirapine were considered possible cases of clinical hepatotoxicity. Patient characteristics, co-medicated drugs, HIV-1 RNA levels and clinical chemistry parameters were collected from outpatient medical records and clinical medical records. RESULTS: At the defined period, 306 patients started a nevirapine-containing regimen, of whom eight developed an acute hepatitis (2.6%) in a median of 24 days [interquartile range (IQR) 20-25 days]. Transaminases peaked at 28 days (IQR, 27-32 days). Injury pattern was in general mixed-hepatocellular. Withdrawal of the antiretroviral agent led to rapid restoration of transaminase levels and resolution of clinical symptoms. The reason for developing this hepatic reaction was not clear in every case as no specific risk factor(s) covering all patients in this case series could be identified. CONCLUSIONS: It is very important to monitor closely transaminase levels of all patients starting a nevirapine-containing regimen, including patients with no specific characteristics that put them at risk. The rapid onset of the clinical symptoms pleads for transaminase monitoring at a very early stage (i.e., within 2 weeks of initiation) of the nevirapine-containing regimen. 相似文献
106.
The urinary excretion of N,N',N"-triethylenethiophosphoramide (thioTEPA), and its metabolites N,N',N"-triethylenephosphoramide (TEPA), N,N'-diethylene,N"-2-chloroethylphosphoramide (monochloroTEPA) and thioTEPA--mercapturate was determined in patients receiving thioTEPA as part of a high-dose combination chemotherapy regimen with cyclophosphamide and carboplatin. The thioTEPA dose was 40 or 60 mg/m(2) in short infusions, twice daily, during 4 days. Urine samples were collected after each voiding on each day of drug administration until 24--48 h after the last thioTEPA infusion. ThioTEPA, TEPA and monochloroTEPA concentrations were determined with gas chromatography and thioTEPA--mercapturate with liquid chromatography--mass spectrometry with direct sample injection. ThioTEPA was present in urine 30 min after infusion and was still excreted 18 h after the last infusion. All metabolites were detected in urine 1 h after infusion. Patients with a creatinine clearance above 140 ml/minl showed higher excretion of TEPA than patients with a creatinine clearance below 140 ml/min (12.8 versus 4.9%, p=0.01). The excretion of monochloroTEPA relative to the excreted amount of TEPA increased at lower pH values of the urine. The excretion of thioTEPA--mercapturate relative to the dose was higher in patients treated with 60 mg/m(2). Excretion of thioTEPA and monochloroTEPA both accounted for only 0.5% of the dose, while TEPA and thioTEPA--mercapturate both accounted for 11.1%. 相似文献
107.
van Heeswijk RP Veldkamp AI Mulder JW Meenhorst PL Beijnen JH Lange JM Hoetelmans RM 《Therapeutic drug monitoring》2001,23(3):255-258
The objective of this study was to evaluate the applicability of saliva as an alternative body fluid for therapeutic drug monitoring of nevirapine. The pharmacokinetics of nevirapine in plasma and saliva during a dosing interval was assessed in HIV-1-infected patients taking nevirapine (200 mg twice daily) to explore the relation between the concentration of nevirapine in plasma and saliva. To validate the anticipated relationship prospectively, single, paired plasma and saliva samples were obtained from nevirapine-treated HIV-1-infected outpatients. The plasma nevirapine concentration was strongly correlated with the salivary concentration. The mean saliva/plasma concentration ratio was 0.51 and was independent of the time after ingestion. Salivary nevirapine concentrations were used to estimate the corresponding plasma concentrations for 31 outpatients. Compared with the true plasma concentrations, the estimated concentrations were biased by -4.2%, with a precision of 13.3%. These data show a strong correlation between the salivary and plasma concentrations of nevirapine at a dosage of 200 mg twice daily. This relation has been validated prospectively, and the prediction of plasma concentrations was accurate and precise. Therefore, the authors conclude that saliva can be a useful body fluid for therapeutic drug monitoring of nevirapine. 相似文献
108.
Excel97在药物分析中的应用 总被引:1,自引:0,他引:1
目的:在药物分析中,电子表格软件MicrosoftExce197for Windows。方法:利用Excel的数据处理功能,进行药物的图表绘制、数据计算和统计处理,回归分析,特别是计算分析,并可建立分析数据库。结果和结论:Excel操作简单,功能强大,数据分析工作直观。 相似文献
109.
目的:比较国产辛伐他汀与进口辛伐他汀治疗原发性高胆固醇血症的疗效及安全性。方法:采用开放区组随机对照、多中心的临床设计。150例高胆 固醇血症病人分为验证组(50例)、对照组(48例)和开放组(52例),剂量均为每晚顿服10mg,服药8周。结果:验证组与对照组服药前后比较,血清总胆 固醇(TC)分别降低26.36%和28.3%,低密度脂蛋白胆固醇(LDL-C)分别降低33.17%和35.51%;验 相似文献
110.
Diet and cancer prevention: the fiber first diet 总被引:3,自引:0,他引:3
Diet can play a major role in cancer prevention. The international
differences in cancer incidence are largely accounted for by lifestyle
practices that include nutrition, exercise, and alcohol and tobacco use.
About 50% of cancer incidence and 35% of cancer mortality in the U.S.,
represented by cancers of the breast, prostate, pancreas, ovary,
endometrium, and colon, are associated with Western dietary habits. Cancer
of the stomach, currently a major disease in the Far East, relates to
distinct, specific nutritional elements such as excessive salt intake. For
these cancers, information is available on possible initiating genotoxic
factors, promoting elements, and prophylactic agents. In general, the
typical diet in the United States contains low levels of the potent
carcinogenic agents, heterocyclic amines, formed during the cooking of
meats. It provides only about half the potent appropriate fiber intake and
is high in calories. About twice as many calories as would be desirable
come from fat, certain kinds of which enhance the development of cancers.
Other foods with functional properties, such as soy products and tea, can
be beneficial. To achieve reduction in risk of certain cancers, diet must
be optimized, primarily to reduce caloric intake and the fat component. The
latter should be 20% or less of total caloric intake and fiber should be
increased to 25- 35 g per day for adults. One approach to achieving these
goals is the Fiber First Diet, a diet designed around adequate fiber intake
from grains, especially cereals, vegetables, legumes, and fruits, which
thereby reduces both calorie and fat intake. Such dietary improvements will
not only reduce cancer and other chronic disease risks, but will contribute
to a healthy life to an advanced age. A corollary benefit is a lower cost
of medical care.
相似文献