Maximal dose ratio

The antagonism is quantified by measuring the ratio of equiactive concentrations of agonist measured in the presence of and absence of the antagonist. These are referred to as dose ratios (DRs). Usually, ECS0 concentrations of agonist (concentration producing 50% maximal... 

General Procedure Dose-response curves to a full agonist are obtained in the absence and presence of the antagonist. At a level of response approximately 30% of the maximal response of the depressed concentration response curve, an equiactive dose ratio for agonist concentrations is measured. This is used to calculate a pA2. 

Equiactive (equieffective) molar concentration (potency) ratios (EMR, EPMR), variants of the term dose ratio or equiactive dose ratios. Usually pertaining to agonists, these are the molar concentrations that produce the same response in a given system. These ratios are dependent on the affinity and efficacy of the agonists and thus are system independent, that is, characterize agonists and receptors in all systems. Care must be taken that the maximal responses of the agonists concerned are equal. 

In BNCT, the first demand is largely determined by the compound chosen. The way of administration, time point of administration in relation to therapy, and the amount administered are important factors. Additionally, the treatment planning plays a role in maximizing the dose ratio. The second demand is determined by the dose prescribed and the treatment plan. Only this aspect is similar to conventional radiotherapy. 

FIGURE 11.27 Patterns of insurmountable antagonism through three different molecular mechanisms. In each case, the concentration of antagonist that produces between a 1.8-fold to a 4-fold shift to the right of the agonist concentration-response curve can be used to calculate the pA2, which, in turn, furnishes a reasonably accurate estimate of the pKB. If depression of the maximal response is observed, then approximately parallel regions of the concentration-response curves should be used to calculate the dose ratios. Redrawn from [11],... 

A key factor in the apphcation of targeted radiotherapy is the need to maximize the tumour to normal ceU radiation dose ratio. In this study, a new series of peptides — including DOTA-Ahx-Oct (OCT), DOTA-Ahx-Ser-Val-Glu-Phe-Ala-Ahx-Oct (P3) and DOTA-Ahx-Gly-Ser-Val-Glu-Phe-Ahx-Oct (P4), where Ahx is epsilon amino hexyl — developed by Whetstone and Meares of the University of California at Davis, United States of America, were evaluated. These peptides include an additional 5 amino acid sequence, which is cleavable by cathepsin. This modification helps to improve the release and trapping of labelled catabolites within the cell [16.2]. These peptides were directly compared with radioiodinated glycated octreotate (Gluc-TOCA), which was shown to have the best internalization properties of the four peptides studied. A comparison of the binding capacity, internalization, exter-nalization and stability of each peptide was carried out under optimized conditions in order to determine their properties. 

In this study, the activity of H2 receptor histamine antagonists was determined in vitro against the histamine-stimulated increase in the rate of beating of the guineapig right atrium at 34°C, by the method described by Parsons et al. [9], Dose ratios (A) were calculated as the ratio of histamine concentrations required to produce half-maximal responses in the presence and absence of different concentrations (B) of antagonist, and dissociation constants (K were derived from the equation K B A- ). The compounds appeared to behave as simple competitive antagonists. 

Pig producers mainly try to approach maximal rates of lean tissue deposition and carcass index values by providing diets formulated to meet all of the known requirements. In the growing period, protein accretion increases as the supply of limiting amino acids increases (Heger et al., 2002). The dose-effect ratio can be subdivided into the nutrition-dependent phase, which is substantially linear, and the plateau phase, which is independent of nutrition supply and whose maximum depends on features of the animals, primarily characterised by the genotype (Susenbeth, 2002). 

The relative proliferative potency (RPP) is the ratio between the minimum concentration of estradiol needed for maximal cell yield and the minimum dose of the test compound needed to obtain a similar effect. The relative proliferative effect (RPE) describes the ratio between the highest cell yield obtained with the chemical and with... 

Induction ofmRNA for pS2 and secretion of cell-type-specific proteins. pS2 was measured in the culture medium of MCF7 cells with the ELSA-pS2 immunoradiometric assay (CIS Bio International, Gif-sur-Yvette, France). Cells were subcultured in 24-well plates for 144 h in 10% CDHuS. The culture medium was centrifuged at 1200g for 10 min to eliminate floating and detached cells. Results are expressed as ng of secreted protein per million cells. The relative-induced protein potency (RIPP) was calculated as 100 X the ratio between the dose of E2 and that of the chemical needed to produce maximal expression of cell-type-specific proteins (pS2). 

RPE was calculated as 100 X (PE-1) of the test compound/(PE-l) of estradiol PE is the lowest concentration needed for maximal cell yield RPP is the ratio between estradiol and compound doses needed to produce maximal yield X 100. All of the compounds that were designated as full or partial agonists (RPE > 15) significantly increased cell yields compared with the controls without hormones (p < 0.05). no effect observed on proliferation. 

A ratio that characterizes the relative effectiveness of a pharmaceutical. It is equal to the maximally tolerated dose divided by the minimal curative or effective dose or, to LD50/ED50. 

Absorption/Disthbution - Maximal serum concentrations (Cmax) occur between 72 to 96 hours postdose. Steady-state serum levels are reached within 5 to 8 weeks of once-weekly dosing. The peak-to-trough ratio at week 48 is approximately 2. 

In order to maximize the therapeutic ratio between efficacy and toxicity, a balance must exist between radiation dose and the volume of the radiation port. The volume of the radiation port affects the amount of radiation that can be given. In regards to toxicity of radiation, total radiation dose is inversely related to the volume of the radiation port... 

It has been suggested that a more realistic estimate of drug safety would include a comparison of the lowest dose that produces toxicity (e.g., LDi) and the highest dose that produces a maximal therapeutic response (e.g., ED99). A ratio less than unity would indicate that a dose effective in 99% of the population will be lethal in more than 1% of the individuals taking that dose. Figure 2.2 indicates that Phenobarbital s ratio LD1/ED99 is approximately 2. 

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