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排序方式: 共有4976条查询结果,搜索用时 15 毫秒
91.
Compressed Donut-Shaped Tablets with Zero-Order Release Kinetics 总被引:5,自引:0,他引:5
Purpose. Simple uncoated compressed tablets with a central hole (donut-shape) are proposed to provide a constant drug release over a long period of time (>20 hrs). The effect of hole size and drug solubility on the release kinetics is investigated.
Methods. The donut-shaped polyethylene oxide (PEO, Mw = 4 × l06) tablets (600 mg and 12 mm diameter) are bored with a drill bit (3/32, 7/64, 1/8, and 5/32).
Results. The release of theophylline from the donut-shaped tablets is zero order (80 – 90% release) before rapidly decreasing. As the hole size is increased from 7/64 to 5/32, the release rate increases and the release time is shortened. However, the release of theophylline from the donut-shaped tablet with a hole size of 3/32 follows the same anomalous release profile from a tablet without a hole. As drug solubility increases, the duration of linear drug release is shortened to 65 – 70% release followed by a severe tailing at the later stage of the release.
Conclusions. Donut-shaped PEO tablets with a hole provide zero-order release kinetics because the effect of the releasing surface area on the release kinetics is reduced. 相似文献
92.
Purpose. The oxidative metabolism of metoprolol was investigated in two human lymphoblastoma cell-lines transfected with variants of cDNA for cytochrome P4502D6.
Methods. The regioselective and enantioselective features of the oxidations of deuterium-labeled pseudoracemic metoprolol were characterized by GC/MS analysis of the substrate and products.
Results. There were significant differences between the two P4502D6 variants in the formation kinetics of O-demethylmetoprolol and -hydroxymetoprolol. The h2D6-Val microsomes highly favored the formation of the O-demethylmetoprolol regioisomer 6.3:1 and 2.8:1, respectively from (R)-metoprolol-d0 and (S)-metoprolol-d2, while the corresponding ratios for h2D6v2 microsomes were much lower. For both variants, O-demethylmetoprolol formation favored the (R)-substrate 1.5 to 2-fold, while -hydroxymetoprolol formation was non-enantioselective. Similar Km values of metoprolol oxidation, 10-20 µM, were observed for the two microsomal preparations.
Conclusions. The regioselectivity, enantioselectivity, and Km values for the h2D6-Val microsomes resemble those observed for the native P4502D6 in human liver microsomes, whereas the h2D6v2 microsomes deviated remarkably in regioselectivity. 相似文献
93.
J. Arly Nelson Anuradha Dutt Luetta H. Allen David A. Wright 《Cancer chemotherapy and pharmacology》1995,37(1-2):187-189
The hypothesis that P-glycoprotein (P-gp) mediates the renal secretion of organic cations was tested by functional expression of mRNAs in theXenopus laevis oocyte system. Efflux of 2-deoxytubercidin (dTub), a substrate for the renal organic cation transporter (OCT) but not for P-gp, was enhanced by injection of renal mRNA but not by injection of mRNA from P-gp-overexpressing cells (MDCK cells transduced with the cDNA for humanMDR1). The functional capacity of the MDCK-MDR mRNA was established by its ability to reduce, the steady-state uptake of a classical P-gp substrate, vinblastine. Thus, these data indicate OCT and P-gp to be distinct entities. TheXenopus oocyte system provides a functional approach to further characterize the OCT.Work supported by NIH Grant RO1DK41606 from the Institute for Digestive Diseases and Kidney, and NIH Cancer Center Core Grant, CA 16672 from the National Cancer Institute 相似文献
94.
The widely used Kt/V concept for quantitating haemodialysis(HD) and ensuring adequate dialysis is based on several assumptions.In order to simplify the urea kinetic modelling, the body isassumed to be a single well-mixed compartment. Previously, morephysiological two-compartment or blood flow distribution modelshave been used to explain the phenomenon of blood urea reboundafter dialysis. This study attempts to evaluate the effectsof a multi compartment model on the removal of urea, i.e. onthe adequacy of dialysis. Four different tissue compartmentsof similar size are used, with flow rates between 40 and 3600ml/min for a bodyweight around 70 kg, allowing for blood flowheterogeneity within and between skeletal muscles. Dialysisis simulated by removing blood containing urea and replacingit with blood free of urea, during isovolumetric conditionsand assuming no diffusion barriers for urea. Several importantconclusions can be drawn from the model. Firstly the removalof urea is dependent both on the time of dialysis and on thenumber of HD treatments per week despite constant Kt/V. Secondlythe blood urea concentration is increased after dialysisureareboundin accordance with clinical data. Thirdlythe concept of blood flow distribution can fully explain thedifference between haemodialysis and peritoneal dialysis interms of Kt/V needed for adequate dialysis. Thus a weekly Kt/Vof 3.6 for HD 4 h 3 times per week removes the same amount ofurea as CAPD and a Kt/V of 2.1. Also, nightly intermittent PDrequires similar Kt/Vs (0.1 higher) as CAPD to obtain equivalentremoval of urea. Finally the crucial point is that the Kt/Vrequired for adequate dialysis must be increased if the dialysistreatment time is reduced. If not, the patient with renal insufficiencysuffers the risk of being under-dialysed. 相似文献
95.
96.
97.
Cook Gary J. R. Lodge Martin A. Marsden Paul K. Dynes Angela Fogelman Ignac 《European journal of nuclear medicine and molecular imaging》1999,26(11):1424-1429
To measure regional skeletal kinetics using fluorine-18 fluoride positron emission tomography (PET) it is necessary to know
the concentration of radioactive tracer being delivered to bone by arterial plasma with relation to time, the arterial input
function (IFa). Methods by which IFa can be derived without arterial sampling are attractive because of their relative technical
simplicity and the reduction in possible morbidity to the subject. We have compared the use of a scaled population input function
(IFp) and a corrected image-derived input function from the aorta (IFi) with an IFa directly measured from a radial artery
line in ten normal postmenopausal women. Both of the aforementioned methods rely only on a small number of discrete venous
samples. Each subject had a dynamic PET acquisition of the lumbar spine performed after the intravenous injection of 180 MBq
18F-fluoride. Both the IFp and the IFi were compared with the IFa in terms of the accuracy of determination of six parameters.
These were: plasma clearance of fluoride to bone mineral (K
i), unidirectional plasma clearance to total bone tissue (K
1) and individual rate constants k
2, k
3 and k
4, calculated using non-linear regression with a three-compartment model, and the plasma clearance to bone mineral calculated
using the Patlak method (K
pat). For both the IFp and the IFi method the root mean square errors for K
pat and K
i were similar and small (<8.2%). The errors in determining K
1 and the rate constants k
2 to k
4 are larger by either method, but with a small advantage using the IFp method. It is concluded that the use of either non-invasive
method for determining the arterial plasma input function is suitable for the measurement of the most important parameters,
K
i and K
pat, in these subjects.
Received 8 April and in revised form 11 July 1999 相似文献
98.
以安替比林为参照物,建立体外人胎盘灌流技术,采用局部胎盘小叶的开放及封闭灌流方法。开放灌充安替比林消除率与时间、母体循环中的浓度无显著相关性,只随流速比的增大而增大,二者之间有显著相关性(r=0906)。封闭灌流两个方向的灌流,供体面安替比林浓度逐渐降低,且都符合指数函数C(t)=Co×e-kt,受体面浓度逐渐升高。两个方面的清除率分别为041ml/min,052ml/min,两者间无显著差异,提取效率母体面到胎儿面方向略低(P<005),分别是683%,289%。以上结果与相关资料一致,说明本室体外人胎盘灌流设备、技术均已完备,结果可靠。 相似文献
99.
Helmuth Adelsberger Nicolas von Beckerath Franz Parzefall Josef Dudel 《Pflügers Archiv : European journal of physiology》1996,431(5):680-689
Single-channel measurements were performed with the aim of constructing a detailed molecular scheme for the reaction between -aminobutyric acid (GABA) and a chloride channel of crayfish deep extensor abdominal muscle (DEAM). GABA was applied in pulses to outside-out patches of muscle membrane, and, based on the dose-response of the peak currents and of their rise times, a linear model with five binding steps has been proposed. Evaluation of the single-channel kinetics indicated at least three open states. Two of them originate most probably from the fully liganded receptor state and are grouped in mixed bursts due to their different life times. The third one appears independently, outside the bursts, and originates from a lower liganded receptor state. Simulations of the dose-responses and the open time distributions with this model led to a set of rate constants which generated relatively optimal fits. 相似文献
100.
The effect of salbutamol on performance in endurance cyclists 总被引:3,自引:0,他引:3
S. R. Norris S. R. Petersen R. L. Jones 《European journal of applied physiology》1996,73(3-4):364-368
The effect of salbutamol (S) on cycling performance was examined in 15 highly trained non-asthmatic male cyclists. A double-blind,
randomized cross-over design was used with S or placebo (P) administered using a metered-dose inhaler and a spacer device
20 min before each testing session. The S dose was 400 μg (four puffs), which is twice the normal therapeutic level. Subjects
were habituated to all the laboratory procedures in the week prior to actual data collection. The subjects performed four
tests under S and P conditions on separate days over 2 weeks. These included measurement of maximal O2 uptake
(cycle ergometry) with assessment of pulmonary function before and after, a submaximal (90% of ventilatory threshold) square-wave
work transition from a base of unloaded cycling, a 60-s modified Wingate test, and a simulated 20 km time trial. No significant
differences were observed in any of the dependent variables related to aerobic endurance or cycling performance between the
S and P conditions. These results support other findings that an acute dose (400 μg) of S has no performance-enhancing properties. 相似文献