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41.
本文将Rowland等人的二房室模型中的消除过程扩展成米氏兼一级消除过程。据此,推导出达到稳态浓度的时间、血药浓度-时间曲线下面积和生物利用度的公式;进而得到平均清除率和剂量间的关系以及剂量与平均清除率和血浆浓度呈线性关系的结论。 相似文献
42.
Renal adaptation to changes in inorganic sulfate intake and age was studied by comparing sulfate uptake by proximal tubule
brush border membrane vesicles (BBMV) from guinea pigs of different ages on relatively high- or low-sulfate diets. Adult (>60
days) or young guinea pigs (<25 days) were fed either a control diet (0.28% sulfur content), a sulfur-free diet, or a high-sulfate
diet. After 5 days on the diet, BBMV were obtained and kinetic analysis of 35sulfate uptake was determined. In adult guinea pigs, the low-sulfate diet produced a significant increase in apparent maximal
velocity (V
max). In young guinea pigs, a lower sulfate intake did not appreciably increase V
max, but a high-sulfate intake produced a reduction in V
max. The affinity for sulfate (K
m) was not changed in either age group. The dietary sulfate intake did not alter sodium gradient dependent-D-glucose or 32phosphate V
max. In conclusion, our data indicate that renal inorganic sulfate BBMV uptake is regulated and responds to conditions of increased
need (i.e., during the growth phase in young animals and during periods of decreased sulfate availability in adult animals)
by increasing BBMV V
max.
Received September 9, 1994; received in revised form March 18, 1997; accepted March 20, 1997 相似文献
43.
参考缓和加氢裂化(MHC)反应机理,开发了一种既能预测产品产率,又能预测产品性质的MHC动力学网络模型。以文献上发表的MHC实验数据为例,进行了参数估计,确定了动力学参数,给出了模型的标准差。本模型所预测的MHC结果,与文献数据吻合良好,具有良好的预测性能。 相似文献
44.
在实验室绝热反应器中进行了乙苯脱氢制苯乙烯的反应动力学研究。根据不同反应机理,提出五种反应模型,经残差分析及模拟计算规律与实验规律的比较,确定Carra双曲模型为最佳反应动力学模型。通过对实验数据的回归拟合,经参数估计求得了速率方程的频率因子和活化能。 相似文献
45.
Marie V. St-Pierre K. Sandy Pang 《Journal of pharmacokinetics and pharmacodynamics》1995,23(3):243-266
Previous mouse liver studies with diazepam (DZ),N-desmethyldiazepam (NZ), and temazepam (TZ) confirmed that under first-order conditions, DZ formed NZ and TZ in parallel.
Oxazepam (OZ) was generatedvia NZ and not TZ despite that preformed NZ and TZ were both capable of forming OZ. In the present studies, the concentration-dependent
sequential metabolism of DZ was studied in perfused mouse livers and microsomes, with the aim of distinguishing the relative
importance of NZ and TZ as precusors of OZ. In microsomal studies, theK
ms andV
maxs, corrected for binding to microsomal proteins, were 34 μM and 3.6 nmole/min per mg and 239 μM and 18 nmole/min per mg, respectively,
forN-demthylation andC
3-hydroxylation of DZ. TheK
ms andV
maxs forN-demethylation andC
3-hydroxylation of TZ and NZ, respectively, to form OZ, were 58 μM and 2.5 nmole/min per mg and 311 μM and 2 nmole/min per
mg, respectively. The constants suggest that at low DZ concentrations, NZ formation predominates and is a major source of
OZ, whereas at higher DZ concentrations, TZ is the important source of OZ. In livers perfused with DZ at input concentrations
of 13 to 35 μM, the extraction ratio of DZ (E{DZ}) decreased from 0.83 to 0.60. NZ was the major metabolite formed although its appearance was less than proportionate
with increasing DZ input concentration. By contrast, the formation of TZ increased disporportionately with increasing DZ concentration,
whereas that for OZ decreased and paralleled the behavior of NZ. Computer simulations based on a tubular flow model and thein vitro enzymatic parameters provided a poorin vitro-organ correlation. TheE{DZ}, appearance rates of the metabolites, and the extraction ratio of formed NZ (E{NZ, DZ}) were poorly predicted; TZ was incorrectly identified as the major precursor of OZ. Simulations with optimized parameters
imporved the correlations and identified NZ as the major contributor of OZ. Saturation of DZN-demethylation at higher DZ concentrations increased the role of TZ in the formation of OZ. The poor aqueous solubility (limiting
the concentration range of substrates usedin vitro), avid tissue binding and the coupling of enzymatic reactions in liver, favoring sequential metabolism, are possible explanations
for the poorin vitro-organ correlation. This work emphasizes the complexity of the hepatic intracellular milieu for drug metabolism and the need
for additional modeling efforts to adequately describe metabolite kinetics.
This work was supported by the Medical Research Council of Canada (MA-9104). 相似文献
46.
T2毒素在灌流大鼠肠肝中的首过效应和代谢动力学 总被引:3,自引:0,他引:3
建立并用大鼠在体肠-肝灌流标本研究了T2毒素在大鼠肠肝中的首过效应和代谢转化动力学,T2毒素在大鼠肠肝中的主要代谢产物是HT2,3′-OHHT2和其葡萄糖醛酸结合物,T2毒素具有显著的肠肝首过效应,当毒素(42μg·ml~(-1))由上肠系膜动脉恒速单次灌流(8 ml·min~(-1))肠-肝标本时,穗态肝、肠抽提率分别为0.978和0.454,总有效清除率为7.91 ml·min~(-1),T2毒素在循环灌流大鼠肠-肝标本中的消除半衰期为6.5min,主要代谢产物HT2,3′-OHHT2的生成半衰期分别为8.5和38.5 min,结果表明,T2毒素经消化道中毒后,在肠和肝的首过代谢下能很快地转化为产物,因此,毒素在体内的毒效作用主要由其代谢产物表现出来。 相似文献
47.
Yukiya Hashimoto Toshiko Koue Yuko Otsuki Masato Yasuhara Ryohei Hori Ken-ichi Inui 《Journal of pharmacokinetics and pharmacodynamics》1995,23(2):205-216
A simulation study was conducted to compare the cost and performance of various models for population analysis of the steady
state pharmacokinetic data arising from a one-compartment model with Michaelis-Menten elimination. The usual Michaelis-Menten
model (MM) and its variants provide no estimate of the volume of distribution, and generally give poor estimates of the maximal
elimination rate and the Michaelis-Menten constant. The exact solution to the Michaelis-Menten differential equation (TRUE)
requires a precise analysis method designed for estimation of population pharmacokinetic parameters (the first-order conditional
estimation method) and also considerable computational time to estimate population mean parameters accurately. The one-compartment
model with dose-dependent clearance (DDCL), in conjunction with the first-order conditional estimation or Laplacian method,
ran approximately 20-fold faster than TRUE and gave accurate population mean parameters for a drug having a long biological
half-life relative to the dosing interval. These findings suggest that the well-known MM and its variants should be used carefully
for the analysis of blood concentrations of a drug with Michaelis-Menten elimination kinetics, and that TRUE, in conjunction
with a precise analysis method, should be considered for estimating population pharmacokinetic parameters. In addition, DDCL
is a promising alternative to TRUE with respect to computation time, when the dosing interval is short relative to the biological
half-life of a drug.
This work was supported in part by the Epilepsy Research Foundation, the Nakatomi Foundation, and a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science, and Culture of Japan. 相似文献
48.
目的探讨极低出生儿体重儿转运过程中的有效护理措施,降低其死亡率。方法通过转运系统将基层医院32例极低出生体重儿转运至新生儿重症监护病房治疗,具体措施包括现场抢救,应用肺泡表面活性物质,途中连续监护和治疗。结果极低出生体重儿32例均成功转运,治愈出院13例,死亡19例,无一例途中死亡。结论全程监护,尽早转运及应用固尔苏是转运成功及降低极低出生体重儿死亡率的关键。 相似文献
49.
Zingraff J.; Caillat-Vigneron N.; Urena P.; Gagne E.-R.; Bererhi L.; Moretti J.-L.; Bardin T.; Drueke T. B. 《Nephrology, dialysis, transplantation》1995,10(2):223-229
Dialysis amyloidosis is one of the most incapacitating complicationsof long-term dialysis treatment. Quantitative assessment ofamyloid deposition using radiolabelled tracers has been recentlyproposed but convincing evidence of its validity in uraemicpatients remains to be provided. We studied the plasma kineticsof i.v. administered 125I-labelled serum amyloid P component(125I-SAP) in 20 chronic haemodialysis patients compared withthose of nine healthy volunteers and three non-dialysed patientswith systemic amyloidosis. Plasma clearance of the tracer wasabnormal in 17 of 20 dialysis patients in whom plasma radioactivitydeclined in a bi-exponential mode, in contrast to the single-exponentialslope observed in all healthy controls. 125I-SAP plasma half-lifeof the second component, probably reflecting metabolic clearance,was significantly prolonged in these dialysis patients comparedwith the healthy controls (35.3 versus 24.6 h, P<0.001).Among the long-term haemodialysis patients the calculated extravasculardistribution of 125I-SAP was significantly greater in thosewith severe arthropathy than in asymptomatic patients. Thesefindings demonstrate for the first time that SAP clearance isdisturbed in haemodialysis patients due to both failing renalelimination and retention in extravascular sites. The extravasculardiffusion is greatly enhanced in patients with clinical evidenceof amyloidosis. Therefore the study of plasma 125I-SAP kineticspromises to be a valuable tool to quantitate the extent of amyloidosis. 相似文献
50.
S. Nakasu Y. Nakasu M. Nakajima M. Yokoyama M. Matsuda J. Handa 《Acta neurochirurgica》1996,138(6):763-770
Summary Cell kinetic study plays an important role in treatment planning of brain tumour patients. MIB-1 antibody has recently become available, which detects Ki-67 antigen even in the formalin-fixed paraffin-embedded specimens. We performed MIB-1 immunostaining in 50 meningiomas and 50 neurinomas, and estimated the cell cycle time (tc) and potential doubling time (Tpot) from MIB-1 staining index (MIB-1 SI) and mitotic index (MI). MIB-1 SI logarithmically correlated with MI in both meningiomas and neurinomas. The tc and the Tpot were expressed as a function of the mitosis time (tm), while the tm is known to be around one hour and not exceeding two hours. When the tm was assumed to be one hour, the average tcs of meningiomas and neurinomas were 6.53±3.56 days and 7.67±3.27 days, respectively. The Tpots were447 × (MIB-1 SI)–1.29 × tm in meningiomas, and490 × (MIB-1 SI)
–0.98
× tm in neurinomas.The tumour doubling times (Tds) were calculated from serial imaging studies in 22 neurinomas and 15 meningiomas. The Tds were formulated as794 × (MIB-1 SI)
–0.83 in meningiomas and1380 × (MIB-1 SI)
–0.97 in neurinomas. Most of the Tds correlated well with the Tpots in meningiomas and neurinomas, and exceeded values of the Tpot when the tm is assumed to be one hour, although a few tumours showed unexpectedly longer Tds. The Tpot and the tc estimated from MIB-1 SI and MI are clinically useful parameters for predicting the growth potential of meningiomas and neurinomas where no other simple methods are available. 相似文献