Minimum effective levels

Infants and children 2 mg/kg. If diuresis is unsatisfactory, increase by 1 or 2 mg/kg, no sooner than 6 to 8 hours after previous dose. Doses greater than 6 mg/kg are not recommended. For maintenance therapy, adjust dose to the minimum effective level. A dose range of 0.5 to 2 mg/kg twice daily has also been recommended. 

Adults and children (older than 12 years of age) Adjust to minimum effective level, usually 800 to 1,200 mg/day. 

Maintenance - Control of pain can usually be maintained with 400 to 800 mg/day (range, 200 to 1,200 mg/day). Attempt to reduce the dose to the minimum effective level or to discontinue the drug at least once every 3 months. 

Microcapsules containing liquid pesticide have certain drawbacks. One example is when the pesticide is itself both volatile and toxic and has a high vapor pressure. A second example is when the capsule shell is strong and thick. In the first case, the pesticide diffuses very rapidly from the capsules and its odor initially repels the pest. Diffusion from the capsules is rapid, however, and when they are empty the pests return to the site (e.g., crops). In the second case, the capsules do not release the pesticide to produce a minimum effective level at the application site, and so pestiddal action is not achieved. In order to overcome these problems, a WO patent disclosed the preparation of microcapsules of pesticides containing pest attractant using a capsule-in-capsule approach [50]. As shown in Figure 5.18, the outer capsule contains pest attractant or food, in which the iruier capsule containing the pesticide, is encapsulated. 

Subchronic Studies. Although short-term repeated exposure studies provide valuable information about toxicity over this time span, they may not be relevant for assessment of ha2ard over a longer time period. For example, the minimum and no-effects levels determined by short-term exposure may be significantly lower if exposure to the test material is extended over several months. Also, certain toxic effects may have a latency which does not allow their expression or detection over a short-term repeated-exposure period for example, kidney dysfunction or disturbances of the blood-forming tissues may not become apparent until subchronic exposure studies are undertaken. 

Amendments to the EC Directives regulating the reclassification of free isocyanate levels came into effect on January 1. Underthe new regulations, TDI prepolymers must be labelled according to the content of free TDI. In preparation for the new regulations, suppliers have been moving to offer finished products with lower levels of free TDI, if possible, to below the minimum required level for hazard labelling. 

Level 1 sampling provides a single set of samples acquired to represent the average composition of each stream. This sample set is separated, either in the field or in the laboratory, into solid, liquid, and gas-phase components. Each fraction is evaluated with survey techniques which define its basic physical, chemical, and biological characteristics. The survey methods selected are compatible with a very broad spectrum of materials and have sufficient sensitivity to ensure a high probability of detecting environmental problems. Analytical techniques and instrumentation have been kept as simple as possible in order to provide an effective level of information at minimum cost. Each individual piece of data developed adds a relevant point to the overall evaluation. Conversely, since the information from a given analysis is limited, all the tests must be performed to provide a valid assessment of the sample. 

The discussion so far in this section has assumed that the treatment groups are unordered. There are, however, situations where these multiple treatment groups correspond to placebo and then increasing dose levels of a drug. It could still be in these circumstances that we are looking to compare each dose level with placebo in order to identify, for example, the minimum effective dose and again we are back to the pairwise comparisons. 

The role of dopamine is discussed more thoroughly in Finder, Chapter 14, in this volume. Several antidepressants are thought to have enhanced antidepressant action attributed to extra effects on the dopamine system. Bupropion, which is available as an antidepressant in the United States only, has an indirect effect on dopamine. An appropriate minimum effective dose was not established in the early clinical trial development program, and the rather high doses used in clinical practice may have contributed to the number of reports of convulsions. The rate, which is acceptable at lower doses of 450 mg/day, rises to unacceptable levels at higher doses [J. A. Johnston et al. 1991). 

To overcome some of these limitations, a fixed dose-titration schedule can be implemented in the beginning of a flexible-dose trial in order to reach a minimum effective dose for each patient, followed by a flexible dose-titration schedule. Use of titration points, anchored to a clinical assessment (e.g. forced titration to the next level in the case of Clinical Global Impression severity scores of > 3), makes the titration schedule and the results more homogeneous and tends to unify investigators judgments (for details see Martenyi et al 2002). 

Fig. 1.4. 5 Shows the administration of 2nd dose between the 7-8 hours interval which maintains the drug plasma levels above minimum effective concentration.

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