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41.
An expedient, rapid, and sensitive capillary gas chromatographic method for the analysis of l,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) or l-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU) in plasma is described. Separation of the underivatized nitrosourea compounds was performed on a 0.33-mm-i.d., 25-m fused-silica, SE-30 capillary column, and detection was carried out using a thermionic N–P-specific detector. The compounds were extracted from plasma with benzene with a yield of >87%. The assay was linear in the ranges of 0.001 to 0.5 and 0.5 to 25 µg/ml for CCNU or 0.003 to 0.50 and 0.5 to 25 µg/ml for BCNU, with correlation coefficients from 0.9914 to 0.9999 and coefficients of variation (CV) of <3.3%. Other antineoplastic agents did not interfere in the assay. The method was employed to study the pharmacokinetics of BCNU in rabbits. The plasma concentration-time curves were fit to a two-compartment model with a mean (SE) , , and total-body clearance of 2.898 (0.913) hr–1, 0.1228 (0.0179) hr–1, and 7.211 (2.862) liters/hr · kg, respectively. Further, the stability of BCNU and CCNU in solution was examined at different temperatures. Both compounds were stable in benzene or acetone (4 to 37°C) but labile in plasma even if refrigerated. The apparent rate constants for degradation of BCNU and CCNU were 0.09921 and 0.02853 hr–1 at 4°C and 5.998 and 2.553 hr–1 at 37°C, respectively. 相似文献
42.
Rosenberg Leonard S. Hostetler Cheryl K. Wagenknecht Dietmar M. Aunet Diane A. 《Pharmaceutical research》1988,5(8):514-517
Esmolol hydrochloride degrades in aqueous solutions by the hydrolysis of a labile aliphatic carboxy-ester group. The products are methanol and ASL-8123. The resulting aliphatic carboxylic acid moiety (ASL-8123) has a pK of 4.80, which is within 1 pH unit of the pH of the formulation. ASL-8123 therefore acts as a secondary buffer and minimizes the change in pH due to degradation. Equations are presented to calculate the change in the pH when the primary degradation product acts as a secondary buffer. This information can be used in the development of a parenteral product to predict, a priori, the concentration of buffer necessary for optimal pH maintenance. This knowledge can reduce the number of formulation screens required to determine the necessary buffer capacity for optimal drug stability. 相似文献
43.
Chien Yie W. Chien Te-yen Bagdon Robert E. Huang Yih C. Bierman Robert H. 《Pharmaceutical research》1989,6(12):1000-1010
Several transdermal contraceptive device (TCD) formulations were developed to provide a dual-controlled transdermal delivery of levonorgestrel (LN), a potent progestin, and 17-estradiol (E2), a natural estrogen. Using a sensitive HPLC method, the in vitro release and skin permeation profiles of LN and E2 from various TCD formulations were simultaneously characterized in the hydrodynamically well-calibrated Valia–Chien skin permeation cells and both were found to follow zero-order kinetics. The rates of drug release and skin permeation were observed to vary significantly depending upon some formulation parameters. Six-month stability studies were performed on seven formulations at room and elevated temperatures (37 and 45°C), and two (Formulations 4 and 5) were found to be acceptable, based on drug recovery, release rate, and skin permeation rate data. Judging from the 6-month accelerated stability studies, it is projected these two formulations will have shelf-life of at least 2 years. As a result of development of an efficient manufacturing process, Formulation 4 was selected for further evaluation. One-week primary skin irritation evaluation in 6 rabbits indicated that Formulation 4 is nonirritating, and it was thus selected for Phase I clinical bioavailability/dose proportionality studies in 12 healthy female volunteers of child-bearing age. Results of pharmacokinetic and pharmacodynamic analyses demonstrated that it is capable of achieving and maintaining a steady-state serum level of LN throughout the 3-week treatment period by weekly applications of one or two TCD patches (10 or 20 cm2). A dose proportionality was obtained in the serum drug levels, daily dose delivered, and contraception efficacy. An excellent correlation was obtained for the rates of transdermal delivery determined by the in vitro studies using human cadaver skin, the in vivo studies in rabbits, and the clinical studies in living subjects. 相似文献
44.
Dr. Jack L. Lewis Cary Keller S. David Stulberg John Steege Michael Santare 《Annals of biomedical engineering》1984,12(6):559-571
Permeability of the soft tissue-bone system surrounding artificial joints fixed in cancellous bone was measured in four adult
dogs after implants had been in place 2 months. Fluid was forced through a cavity formed by removal of the implant, the cavity
was capped with a stopper to allow for pressure generation. Surface permeability of the 2-month-old implant cavity was 45
times less than the permeability of freshly drilled holes in cancellous bone. A mathematical model of a rigid implant resting
on a biphasic solid-fluid layer showed the fluid carried 90% of the load when the implant cavity permeability was assumed,
but only 27% when the freshly drilled permeability was used. The results suggest caution in interpreting finite-element models
with bonded interfaces and suggest a possible role of the fluid in biological response at the interface. 相似文献
45.
中国少年智力量表(CISJ)编制及其常模 总被引:5,自引:1,他引:5
目的:编制一套适用于我国少年期的智力量表。方法:以年龄10~15岁少年为对象,参考第五次人口抽样调查资料,按分层随机原则取样,根据测验结果和标准化程序建立常模。结果:总体样本取得的原始分,按城乡各7个常模年龄组,分别换算出各分测验的量表分,然后建立了总体样本的智商、能力商、智力因素商和智商百分位等常模。样本智商接近于正态分布。信度和效度较高。结论:CISJ可以作为智力诊断工具应用于临床。 相似文献
46.
Joseph K. Kovach 《Behavior genetics》1993,23(4):369-377
Successful artificial selection of quail (C. coturnix japonica) for divergent early approach preferences for, and imprintabilities to, the wavelength characteristics of otherwise identical visual stimuli decreased the trait's developmental stability. The developmental error that resulted from selecting for extreme initial preferences was associated with enhanced imprintabilities. Conversely, the developmental error that resulted from selecting for extreme imprintabilities was associated with enhanced expression of directional gene effects in extreme initial preferences. The data are attributed to selectively relaxed normative canalization of trait development, and to related enhanced expression of genetic, environmental, and stochastic influences in trait deviations. 相似文献
47.
流行性乙型脑炎病毒活疫苗株SA14-14-2基因稳定性研究 总被引:1,自引:0,他引:1
目的 通过研究流行性乙型脑炎活疫苗减毒株基因稳定性,从分子水平证实流行性乙型脑炎活疫苗的遗传稳定性。方法分析流行性乙型脑炎活疫苗主种子、工作种子及其相应的疫苗病毒E蛋白基因核苷酸和氨基酸序列,并与其强毒株和基因库中乙脑病毒减毒株(AF15119)比较。结果乙脑活疫苗主种子、工作种子及其相应的疫苗病毒的E蛋白基因核苷酸序列完全相同。这些病毒E蛋白的氨基酸序列与基因库中乙脑病毒弱毒株(AF315119)比较显示第E447位点氨基酸有差异。结论乙脑病毒活疫苗减毒株遗传学特性稳定。 相似文献
48.
The chemistry and structure of the dimethacrylate resins and the nature of the filler systems in dental composite resins are reviewed in relation to their influence on the setting behaviour, dimensional stability, aesthetics, fracture behaviour and adhesive potential. It is clear that a deeper understanding of the structure of the polymeric matrix and the mechanism of clinical wear is required. As a result of ongoing research in this area and with the development of dentine adhesives, the future prospects of composite resins are encouraging. 相似文献
49.
A high frequency transformation system has been developed for Penicillium paxilli using pAN7-1. Up to 44% of the primary transformants were heterokaryons. Loss of hygromycin resistance was observed in primary transformants that were sub-cultured on non-selective media, but single spores of these primary transformants were mitotically stable on both selective and non-selective media. A molecular analysis of the transformants generated showed that 78% had single-site integrations, with half of these containing a single copy of pAN7-1. CHEF-gel electrophoresis showed that P. paxilli has at least six chromosomes with a total genome size of about 23.4 Mb. 相似文献
50.
T. D. Brown J. Patterson Stone J. H. Schuster D. C. Mears 《Medical & biological engineering & computing》1982,20(6):727-733
The effectiveness of external fixation in the stabilisation of pelvic ring fractures was studied in a laboratory cadaveric series. Shearing displacements occurring at sacroiliac joint and symphysis pubis dislocation sites, due to simplified longitudinal loading of the sacrum in an Instron unit, were monitored using variable-impedence transducers. The rigidity of fixation was compared for the Slätis and the Bonnel single anterior frames, for coupled and uncoupled double anterior frames, and for combined anterior-plus-posterior fixation achieved with separate transfixation pin clusters, with through-and-through pin clusters, or with a posterior screw plate. The data showed that the use of posterior fixation provided greatly enhanced stabilisation compared to that achieved with anterior fixation alone. The complex double anterior frames performed only slightly better than did the simpler single anterior frames. In no case, however, was it possible to recover rigidity levels approaching those of the intact pelvis. The results suggest that the transfixation pin arrangement is the most important determinant of pelvic fixation stability, and that further investigation of posterior screw-plate fixation is warranted. 相似文献