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1.
Rik C. Schoemaker Joop M. A. van Gerven Adam F. Cohen 《Journal of pharmacokinetics and pharmacodynamics》1998,26(5):581-593
The most widely applied model relating drug concentrations to effects is the Emax
model. In practice, concentration–effect relationships often deviate from a simple linear relationship but without reaching a clear maximum because a further increase in concentration might be associated with unacceptable or distorting side effects. The parameters for the Emax
model can only be estimated with reasonable precision if the curve shows sign of reaching a maximum, otherwise both EC50
and Emax
estimates may be extremely imprecise. This paper provides a solution by introducing a new parameter (S0
) equal to Emax/EC50
that can be used to characterize potency adequately even if there are no signs of a clear maximum. Simulations are presented to investigate the nature of the new parameter and published examples are used as illustration. 相似文献
2.
The aqueous humor concentration of phenylephrine and its corresponding mydriatic response were measured over time in New Zealand albino rabbit eyes following a 10-µl topical instillation of a phenylephrine HC1 viscous solution (10%) or a phenylephrine oxazolidine (prodrug) suspension in sesame oil (1 and 10%). The bioavailability of a 1% prodrug suspension in the rabbit eye (AUC of aqueous humor concentration vs time) was 30% lower than that of a 10% phenylephrine solution (P < 0.1) with the exception that the peak time occurred 34 min earlier with the prodrug. A 10% prodrug suspension increased the aqueous humor bioavailability approximately eightfold but improved the mydriatic activity (AUC of mydriasis vs time) only fourfold. The pharmacokinetic parameters, apparent absorption, and elimination rate constants, of phenylephrine and the prodrug were determined from aqueous humor concentration–time and mydriasis–time profiles. The study showed that the kinetic parameters of phenylephrine estimated from its mydriasis profile do not accurately reflect the kinetics of drug distribution in the iris. These parameters also varied with the instillation of phenylephrine solution or prodrug suspensions. A mydriatic tolerance of the pupil response was apparent after the topical instillation of phenylephrine solution. The mydriatic tolerance may be due to the decrease in receptor number in the iris dilator muscle. 相似文献
3.
The influence of different levels of enflurane anaesthesia on infusion requirements of vecuronium was studied in 40 adult surgical patients. Ninety percent neuromuscular block was maintained by computer controlled infusion of vecuronium. During the first 90 min study period all patients received fentanyl-nitrous oxide-oxygen (2:1) anaesthesia. For the following 90 min the patients were randomly assigned to receive enflurane at different end-tidal concentrations: group I, control, fentanyl-nitrous oxide anaesthesia; group II, enflurane 0.3%-nitrous oxide; group III, enflurane 0.6%-nitrous oxide; group IV, enflurane 0.9%-nitrous oxide. Every patient served as his/her own control and the changes of vecuronium infusion requirements were determined individually. When the administration of enflurane was started, vecuronium infusion requirements decreased progressively until 90 min. In group II the infusion rate lowered from 80±28 to 56±20 μg . kg-1 . h -1 , in group III from 61 ±29 to 34±17 μg . kg-1 . h-1 and in group IV from 65±20 to 30± 14 μg . kg-1 . h-1 . In the control group the infusion rate decreased during the three hour study period from 69± 17 (first 90 min period) to 59± 16 μg . kg-1 . h-1 (second 90 min period). Enflurane reduces the dose requirements of vecuronium administered by continuous infusion in a dose- and time-dependent manner. 相似文献
4.
Tun Li Myung G. Lee Win L. Chiou 《Journal of pharmacokinetics and pharmacodynamics》1986,14(5):495-509
Effects of differences in the rate and composition of intravenous fluid replacement for urine loss on the pharmacokinetics and pharmacodynamics of furosemide were evaluated using the dog as a model animal. Each of six dogs received 8-hr constant intravenous infusion of 20 mg (15 mg used in one dog) of furosemide with 0% replacement (treatment I), 50% replacement (treatment II), and 100% replacement (treatment III) with lactated Ringer's solution, as well as with 100% replacement with 5% dextrose in water (treatment IV). Most pharmacokinetic parameters, such as plasma clearance, steady-state volume of distribution, mean residence time, and terminal half-life, were essentially the same in all four treatments. Renal clearances and urinary excretion rates of the drug in treatments II–IVwere essentially the same, but about 20% higher than those in treatment I.In spite of the similarities in kinetic properties, diuretic and/or natriuretic effects from furosemide were markedly different among the four treatments. For example, mean 10-hr urine outputs were 646, 1046, 3156, and 1976 ml and mean 10-hr sodium excretions were 87.0, 142, 383, and 97.2 mmole for treatments I–IV,respectively. Except for treatment III,diuresis and/or natriuresis were found to be time-dependent, generally decreasing with time until reaching a low plateau during later hours of infusion. The present findings also showed that (1)no fluid replacement and 100% replacement with 5% dextrose solution both produced the same degree of severe acute tolerance in natriuresis, indicating the insignificance of water compensation in tolerance development; (2)in treatment II,where neutral sodium balance was achieved, the development of acute tolerance in diuresis and natriuresis can mainly be attributed to negative water balance under this special condition; (3)at steady state the hourly diuresis and natriuresis could differ up to about ten times between treatments. Some implications for the kinetic/dynamic relationship or modeling, in the clinical use, and in the bioequivalence evaluation of dosage forms are discussed. 相似文献
5.
益肾化浊注射液对慢性肾功能衰竭大鼠残余肾中细胞因子含量的影响 总被引:2,自引:0,他引:2
通过观察益肾化浊注射液对5/6肾切除大鼠残余肾中细胞因子含量的影响,益肾化浊注射液延缓慢性肾功能衰竭(CRF)模型大鼠肾功能减退的作用机理。结果显示:益肾化浊注射液可以降低5/6肾切在鼠血清肌,尿素氮(P<0.01),下调肾组织中白细胞介素-1(IL-1)(P<0.05),白细胞介素-8(IL-8)(P<0.05)及肿瘤坏死因子(TNF)(P<0.05)的总体水平,说明益肾化浊注射液可以通过下调5/6肾切除大鼠残余肾中相关细胞因子含量,抑制促炎细胞因子对肾脏的损害,从而延缓CRF的进展。 相似文献
6.
7.
米非司酮作用于兔输卵管收缩活动与Ca^2+关系的研究 总被引:1,自引:0,他引:1
通过“结合化学分离与原子吸收分光光度法”对Ca^2 含量测定和离体输卵管肌条收缩记录方法,研究米非司酮(Ru486)对增加假孕(4d)兔输卵管平滑肌收缩频率,而不改变其收缩张力和振幅时与Ca^2 之间的关系,结果提示:(1)Ru486对输卵管分泌液和组织内Ca^2 的含量分布无明显影响;(2)Ru486具有降低细胞外液高Ca^2 浓度促Ca^2 内流,而使收缩增强的效应,且能协同Ca^2 通道阻断剂(Verapamil)抑制细胞外Ca^2 内流,而致收缩减弱的效应。 相似文献
8.
9.
本文观察了益肾通淋汤对大鼠实验性草酸钙结石的防治实验。结果表明,实验组在草酸钙晶体数和聚体数、肾小管扩张数,肾钙含量等方面均少于对照组(P<0.05或P<0.01);同时观察了实验大鼠肾脏的一般组织学改变,可见对照组肾小管上皮细胞浊肿变性,甚至细胞崩解、细胞碎片,胞核和刷状堟PAS阳性物质脱落于管腔内,有的与结石晶体粘附,肾小管明显扩张,而实验组未见明显的组织学损害。因而认为益肾通淋汤可能是通过抑制草酸钙结晶的析出和聚集,改善肾组织细胞的代谢和功能,减少细胞器脱落成为结石核心和基质物质以及加速尿液排泄,促进微结石排出的途径而起到防治尿结石作用的。 相似文献
10.
吸附澄清法在中药水提液澄清中的应用研究 总被引:30,自引:1,他引:29
采用吸附澄清法使中药水提液澄清,从工艺稳定性,成分分析,药效学实验及效益分析四方面分析了两种工艺,吸附澄清法同水提醇沉法相比,能更有效地保留中药总固体物含量及有效成分,提高制剂成品的内在质量;成品稳定性好;成本低;生产周期短;劳动强度低,可望产生良好的社会经济效益。 相似文献