Dose issues

Another category of potential confounding variables includes dosing issues. Caffeine researchers have administered a wide variety of experimental dosages, an issue related obviously to physiological effects but also of interest to those concerned with caffeine doping. The timing of the... 

Kinnett D. Botulinum toxin A injections in children technique and dosing issues. Am J Phys Med Rehabil. 2004 83(suppl) S59-S64. 

Several applications of subtraction method are listed in Table 15.2. The method is probably best employed when one has an initial hypothesis so that the subtraction can be designed to isolate genes that are responsible for the postulated effect. To achieve an effective subtraction, not only is the selection of compound for subtraction critical, but the pair of compounds of study should also be applied at an equipotent dose, of which an accurate determination could require additional studies. In a comparative study of two hepatotoxi-cants TCDD and TCDF,25 the equipotent dose issue has been elegantly explored by using toxic equivalency factors (TEFs) based on endpoint-specific relative potencies. 

UREX + 1 UREX + la U (highly purified) U (highly purified) Tc, 1 (LLFPs, dose issue) Tc, 1 (LLFPs, dose issue) Cs, Sr (short-term heat mgmt.) Cs, Sr (short-term heat mgmt.) Other FPs FPs (including lanthanides) TRU + Ln (Temporary storage) TRU (group extraction) ... 

Equipment module The equipment-specific functionality that provides the actual control capability for equipment including procedural, basic, and coordination control, and is not part of the recipe. An equipment module may involve one or more control modules around a piece of process equipment. In dosing issue, a set of valves or pump flow measuring instrument is an equipment module. 

Approximately 500,000 Americans suffer strokes each year. Many of the 80% that survive suffer paralysis and impaired vision and speech, often needing rehabiUtation and/or long-term care. Hence, whereas treatment using rt-PA is likely to be expensive (costs are 2200/dose for treating heat attacks), the benefits of rt-PA could outweigh costs. In the case of heart attacks, the 10 times less expensive microbiaHy derived streptokinase can be used. There is currentiy no competing pharmaceutical for treatment of strokes (18,19). Consequentiy, the cost of manufacture of rt-PA may not be as dominant an issue as would be the case of other types of bioproducts. 

Process Rationale. The products of plasma fractionation must be both safe and efftcaceous, having an active component, protein composition, formulation, stabiUty, and dose form appropriate to the intended clinical appHcation. Processing must address a number of specific issues for each product. Different manufacturers may choose a different set or combination of unit operations for this purpose. 

Another important consideration for providing uniform implantation involves the geometry of the ion beam with respect to the target surface. Too high an angle from normal incidence leads to excessive sputtering and low retained dose. These issues and others pertinent to practical aspects of implantation treatment have been discussed (35,165). 

Thus, a drug may produce response either with low efficacy by occupying many receptors or with high efficacy by occupying few receptors. The issues of dealing with agonist—dose response relationships can be complex and reference should be made to detailed texts (44,45). 

Altliough the technical conununity has come a long way in understanding how to do a better job in luizard identification, dose-response assessment, and exposure assessment portions of risk assessment, it lias only begun to understand how to best cluiractcrize hcaltli risks and how to present tliese risks most appropriately to both the public and decision makers. Tlie next tliree sections specifically address tlicse issues. Tliis section deals witli qualitative risk assessment while tlie next two sections deal witli quantitative risk assessment. 

In a study with captive male American kestrels (Drouillard et al. 2001), birds were dosed with Aroclor-contaminated diet and the toxicokinetics of 42 PCB congeners contained therein was stndied. Those congeners that were most rapidly cleared contained vicinal meta-para hydrogen substituents on at least one phenyl ring. This provides further evidence for the importance of open (i.e., not substituted by chlorine) meta-para positions for metabolic attack, an issue that will be returned to in the next section (Section 6.2.3). 

Optimal use of epinephrine autoinjectors for first-aid treatment of anaphylaxis in community settings is hampered by several issues. In most countries, these include the availability of only two pre-measured epinephrine doses and only a few different needle lengths, and the need to replace outdated autoinjectors at 12- to 18-month intervals due to degradation of the epinephrine solution they contain. 

Cl. Dybing, E. et al.. Hazard characterization of chemicals in food and diet dose response, mechanisms and extrapolation issues. Food Chem. Toxicol, 40, 237, 2002. 

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