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131.
根据桂枝汤的效应消除半衰期和表观消除半衰期制订给药方案的探讨 总被引:3,自引:0,他引:3
为探讨药效法估测的效应消除半衰期和效量法估测的表观半衰期对合理制订给药方案的意义和作用,以桂枝汤解热和抗炎的药物动力学实验中所得的相应参数值设计了给药方案,观察了它们在提高药效上的作用。结果表明在给药总剂量相等、首次给药同时开始的情况下,以半衰期设计的给药方案组的药效均明显高于习惯的一次给药组;而以效应消除半衰期设计给药方案组药效增强率又高于以表观半衰期设计的方案组。提示效应消除半衰期比表观半衰期似更有实践意义。 相似文献
132.
Antimetastatic Activity of Polymeric RGDT Peptides Conjugated with Poly(ethylene glycol) 总被引:1,自引:0,他引:1
Ikuo Saiki Junya Yoneda Yu Igarashi Miho Aoki Naoto Kusunose Kei-ichi Ono Ichiro Azuma 《Cancer science》1993,84(5):558-565
Polymeric peptides containing defined repetitive or cyclic structures of RGDT sequence, (RGDT)n (n = 1 to 11) and cyclo(RGDT)n (n=2 to 4), at a dose of 500 μg exhibited an inhibitory effect on experimental lung metastasis upon co-injection with tumor cells and the magnitude of the effect increased in parallel with the increase of degree of repetition of the RGDT sequence. The conjugation of (RGDT)n (n = 1, 5, 11) with poly(ethylene glycol), PEG as a polymeric carrier led to enhanced inhibition of lung metastasis in proportion to the degree of RGDT sequence repetition and in a dose-dependent manner. Multiple i.v. administrations of PEG-(RGDT)11, at 2-day and 3-day intervals before the excision of primary tumors, effectively inhibited spontaneous lung metastasis by s.c. inoculation of tumors, whereas (RGDT)11 exhibited inhibition of lung metastasis only when given at 2-day intervals. This indicates that the conjugation of PEG with (RGDT)n allowed the prolongation of administration interval, implying a sustained inhibitory effect on tumor metastasis. In support of this supposition, a decrease in the arrest of radiolabeled tumor cells in the lungs was observed when PEG-(RGDT)11 was co-injected i.v. with tumor cells, or injected i.v. one day before tumor inoculation. In contrast, (RGDT)11 significantly inhibited the tumor cell arrest in the lungs only upon co-injection with tumor cells. We also noted that (RGDT)n, cyclo(RGDT)n and PEG-(RGDT)11 inhibited tumor cell invasion into Matrigel in a concentration-dependent manner and in proportion to the degree of RGDT sequence repetition, indicating that the peptide-mediated antimetastatic effect is partly associated with the anti-invasive potential. Thus, the conjugation of anti-cell adhesive and antimetastatic RGDT peptide with PEG might provide a therapeutically promising basis for the prevention of cancer metastasis (“anti adhesion therapy”). 相似文献
133.
JOHN CHALMERS 《British journal of clinical pharmacology》1996,42(1):29-35
1 A 'retrospective' of the development of the drug treatment of hypertension is presented from the early days of ganglion blockers to the present time together with a review of the evidence of benefit from treatment.
2 Current issues and debates are summarised including shortfalls in the control of hypertension in populations, difficulties surrounding the measurement of blood pressure, disagreement on the levels of blood pressure to treat, the goal blood pressures to aim at, issues surrounding lifestyle measures such as the low salt diet and low intensity exercise, and treatment with diuretics and with calcium antagonists.
3 A 'perspective' is presented on some avenues for progress in the years ahead. These will include the identification of genetic markers to determine the hypertensive individuals with the greatest risk of death and of cardiovascular complications. 相似文献
2 Current issues and debates are summarised including shortfalls in the control of hypertension in populations, difficulties surrounding the measurement of blood pressure, disagreement on the levels of blood pressure to treat, the goal blood pressures to aim at, issues surrounding lifestyle measures such as the low salt diet and low intensity exercise, and treatment with diuretics and with calcium antagonists.
3 A 'perspective' is presented on some avenues for progress in the years ahead. These will include the identification of genetic markers to determine the hypertensive individuals with the greatest risk of death and of cardiovascular complications. 相似文献
134.
135.
Ross D. King Jonathan D. Hirst Michael J. E. Sternberg 《Perspectives in Drug Discovery and Design》1993,1(2):279-290
Summary Neural networks and machine learning are two methods that are increasingly being used to model QSARs. They make few statistical assumptions and are nonlinear and nonparametric. We describe back-propagation from the field of neural networks, and GOLEM from machine learning, and illustrate their learning mechanisms using a simple expository problem. Back-propagation and GOLEM are then compared with multiple linear regression (using the parameters and their squares) on two real drug design problems: the inhibition ofEscherichia coli dihydrofolate reductase (DHFR) by pyrimidines and the inhibition of rat/mouse tumour DHFR by triazines. 相似文献
136.
K. L. Preston K. L. Preston E. C. Strain G. E. Bigelow J. T. Sullivan K. L. Preston 《Psychopharmacology》1996,123(1):15-25
The present study was conducted to determine whether methadone maintenance alters the pharmacodynamic effects of single doses of cocaine. Twenty-two current users of IV cocaine who were not seeking treatment for their illicit cocaine use participated while living on a research unit. Eleven were maintained on methadone 50 mg PO daily as treatment for their opioid abuse; 11 were opioid abusers who were not physically dependent on opioids and who provided opioid-free urines throughout the study. Each subject received acute cocaine challenge doses of 0, 12.5, 25, and 50 mg intravenously in random order under double-blind conditions in separate test sessions. Physiologic and subject-rated responses were measured before injection and for 2 h after. In the methadone maintenance group, cocaine challenge sessions occurred 15.5 h after the daily methadone dose. There were significant differences between the methadone-dependent and nondependent groups: 1) baseline differences related to chronic methadone administration and not associated with cocaine administration (lower respiration rates and pupil diameter; higher skin temperature) and 2) differences in response to cocaine administration; cocaine-induced increases in subject ratings of Drug Effect, Rush, Good Effects, Liking, and Desire for Cocaine and in heart rate were greater in the methadone maintenance patients compared to the non-dependent group. These results indicate that the positive subjective effects and some physiological effects of cocaine are enhanced in methadone-maintained individuals, suggesting a pharmacological basis for the high rates of cocaine abuse among methadone maintenance patients.Some of these data were presented at the annual meeting of the Committee on Problems of drug Dependence, Keystone, Colorado, June 1992 相似文献
137.
The daily fluid intake of male Wistar rats with simultaneous access to 6% ethanol and water was determined during a baseline period (1 week), following adrenalectomy (1 week) and for 3 weeks following SC implantation of hormone pellets containing corticosterone (CORT) or dexamethasone (DEX). Ethanol consumption dropped during the first week of adrenalectomy (ADX) but increased again in the absence of hormone replacement to reach preoperative levels during the ensuing weeks. The CORT treatment, which produced plasma hormone levels similar to the 24-h mean concentration of adrenally intact rats, not only reversed the effect of ADX on alcohol consumption but also enhanced it to levels above those observed in intact rats. Water intake was not affected by the CORT treatment. DEX implants stimulated water intake, but did not enhance the drinking of ethanol. SC injections of RU 28318 (type I corticosterone receptor antagonist; 10 mg/kg) or mifepristone (RU 38486; type II receptor antagonist; 25 mg/kg) at the beginning and halfway through three daily, 6-h tests failed to affect ethanol drinking in adrenally intact rats or in ADX rats bearing CORT implants. Similarly, there was no effect of giving the two antagonists in combination. These results suggest that exogenous CORT can induce excessive alcohol intake in genetically unselected rats and that this facilitatory effect may be mediated by non-genomic cellular mechanisms. 相似文献
138.
Buprenorphine, a partial mu-opioid receptor agonist, has been proposed as a treatment for cocaine abuse. However, studies
in animals have produced conflicting results on the nature of the interaction between buprenorphine and cocaine. In some studies,
buprenorphine attenuated the effects of cocaine and in others it enhanced them. The purpose of the present study was to evaluate
the interaction of buprenorphine and cocaine on the rotational behavior of the nigrally-lesioned rat. Both buprenorphine (0.003–0.1
mg/kg) and cocaine (1.0– 30 mg/kg) alone produced dose-dependent increases in rotational behavior. Buprenorphine produced
long-lasting turning with a peak at 60 min after administration, while cocaine produced turning that peaked immediately after
administration and lasted for about 2 h. To distinguish simple additivity from other possible outcomes, we determined the
relative potency of each drug alone, using a defined level of effect: 150 turns above the saline control in 4 h. This effect
was produced by 10.0 mg/kg cocaine alone and by 0.0175 mg/kg buprenorphine alone. Based on these results, fixed ratio combinations
were tested and the experimentally derived effects were compared to the theoretically additive values, using an isobolographic
analysis. The fixed ratio combinations of the two drugs tested produced turning greater than predicted from simple additivity.
This finding provides statistically-supported evidence for synergism between the actions of buprenorphine and cocaine.
Received: 28 January 1997 / Final version: 7 June 1997 相似文献
139.
对71例肾移植术后患者进行了氨苄青霉素与环孢菌素的相互作用研究。患者在开始服用氨苄青霉素之前、之中、之后的肾功能以及环孢菌素全血浓度测定结果表明,三项指标均无显著改变。另一组肾移植术后患者37例进行的诺氟沙星与环孢菌素相互作用研究,结果与氨苄青霉素的相互作用类似。提示氨苄青霉素、诺氟沙星可安全地与环孢菌素合用,而不影响肾功能。 相似文献
140.