Dose response profiles

After about 30 training sessions, most animals had acquired the PCP vs. vehicle discrimination, as evidenced by at least 9 out of 10 consecutive sessions during which the rats emitted fewer than 20 responses before the first reinforcement. Following this acquisition of the discrimination, the animals were tested in a random order with different doses of PCP. Figure 1 shows the dose-response profile for PCP discrimination in different groups of rats trained to discriminate 1.0, 1.78 or 3.2 mg/kg of PCP from vehicle. At low doses of PCP few, if any, rats chose the lever previously paired with PCP (i.e., most rats chose the vehicle-associated lever). 

Both toxins exhibit similar dose-response profiles and both toxins elicit the apparent hypothermia to the same extent and for the same duration. This response, whether promoted by the fish toxin or the dinoflagellate toxin, is reversed by increasing ambient temperature. In addition, both toxins evoke equivalent gross symptoms of malaise. These similarities in biological traits suggest that more than a casual relationship exists between ciguatoxin and maitotoxin. 

Figure 5.9. Dose-response profile in a population. (A) Relationship between responding patients, expressed as percentage of individuals, and plasma drug concentrations. With increasing drug concentration, the proportion of patients who derive therapeutic benefit, without concentration-limited side effect peaks, and then declines. (B) A schematic representation of dose-response curves. Typical therapeutic and lethal responses at indicated doses are evaluated in animal models to estimate therapeutic index, TI. ED50, effective dose needed to produce a therapeutic response in 50% of animals, exhibiting therapeutic response LD50, effective dose needed to produce lethal effects in 50% of animals.

Linn, W.S., and J.D.Hackney. 1983. Short-Term Human Respiratory Effects of Nitrogen Dioxide Determination of Quantitative Dose-Response Profiles. Phase 1. Exposure of Healthy Volunteers to 4 ppm N02. CRC-CAPM-48-83.(l-82). Final Report. Rancho Los Amigos Hospital, Inc., Downey, CA. NTIS PB84-132299. 30 pp. 

Linn, W.S., and J.D.Hackney. 1984. Short-Term Human Respiratory Effects of Nitrogen Dioxide Determination of Quantitative Dose-Response Profiles. Phase 2. 

LMW heparins are less protein bound and have a predictable dose-response profile when administered s.c. or i.v. They also have a longer t/ than standard heparin preparations. 

The process we have taken to develop a cotton-based wound dressing containing a fiber-inhibitor is outlined in Figure 1. The goal of this process is integration of a chemical modification with the cotton fiber textile design compatible with the wound environment. In vitro assessment of fiber-inhibitor formulations is necessary to demonstrate the relative inhibition kinetics on the textile fiber. The dose response profile of the protease fiber-inhibitor may then be utilized as a benchmark for... 

Consider the drug dose-response profile shown in Figure 8.1. 

Figure 8.1 Drug dose response profile for a hypothetical drug, showing the absorption and elimination phases following administration.

Plant physiologists and other biological scientists also have their important role to play in allelopathy. They must devise suitable bioassays to detect the suspected allelopathic compounds, follow the biological activity of the individual and associated chemicals, develop activity profiles for identified chemicals, and determine the conditions (dose/response) for chemicals to arrive at the threshold levels. They must also determine which chemicals contribute... 

Therapeutic confirmatory (Phase III) Demonstrate/confirm efficacy Establish safety profile Provide an adequate basis for assessing the benefit/risk relationship to support licensing Establish dose-response relationship Adequate and well controlled studies to establish efficacy Randomized parallel dose-response studies Clinical safety studies Studies of mortality/morbidity outcomes Large simple trials Comparative studies... 

Establish a dose-response pharmacodynamic profile by using initial doses projected to be therapeutic in humans. The dose required is predicted on the basis of blood levels found in animal screens. 

Notes Analysis (Joost and Methner, Genome Biol., 3(11) research 0063.1-0063.16,2002. http //genomebiology.com/ 2002/3/11 /research/0063). Profiling is performed in two phases. The first phase consists of a panel of 25 GPCR representing the families most commonly associated with off-target effects. Once a compound shows activity in one of the assays from the first set, full dose response is run on receptors within the same target family to assess selectivity (Phase 2). 

Figure 6.22 PWG assay dose precision profiles of multiplexed three-analyte immunoassay for two sets of experiments. Dose precisions correspond to standard deviations of analyte concentrations that were back-calculated using corresponding dose response curves. (From Pawlak, M. et al., Proteomics, 2, 383-393, 2002. With permission.)...

Estabhsh safety profile Randomised parallel dose-response studies... 

Phase III studies represent the confirmatory phase of drug development, which takes several years and usually involves several thousand patients at multiple trial centers. Large patient numbers are required in these trials to provide convincing documentation of clinical efficacy and safety, a more complete adverse event profile and covariates and estimates of variability in dose response relationship due to individual differences in pharmacokinetics and pharmacodynamics. They are aimed at definitively determining a drug s effectiveness and side-effect profile. Most of these studies are double-blind and placebo-controlled, sometimes with the option of open-label long-term extensions. 

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