Activity and Dose

Adams J (1993) Structure-activity and dose-response relationships in the neural and behavioral teratogenesis of retinoids. Neurotoxicol Teratol, 15(3) 193-202. 

Pharmacokinetic data were collected as well as pharmacodynamic measurements of platelet aggregation support (ristocetin cofactor activity) and cuticle wound blood flow. An important component of these studies was the suitability of the model. These models were chosen because of the biochemical deficiency of the particular factors and the parallel clinical syndromes. Such in vivo data can help in determining activity and dosing when such a product is first used in human trials. The Refacto molecule was also studied in rats and monkeys to determine its no observed adverse effect level, that was more than 10 times normal circulating levels. The major toxicity observed was the development of antibodies to the molecule that blocked activity and resulted in an acquired hemophilia syndrome. Similar findings were demonstrated when plasma-derived material was injected into monkeys [20]. 

The formulation and product presentation may require adjustments as the product progresses through clinical studies. Concentration of the active and dose content may be adjusted for materials in later clinical studies. If the changes are nominal, then there may be little need for adjustment to the process. Significant changes warrant further development as the lyophiliza-tion processing conditions require refinement and may require subsequent scale-up studies. 

The anthranoids produce harmless discoloration of the urine. Depending on intrinsic activity and dose, they can also produce abdominal discomfort and cramps, nausea, violent purgation, and dehydration. They can be distributed into breast milk, but not always in sufficient amounts to affect the suckling infant. Long-term use can result in electrolyte disturbances and in atony and dilatation of the colon. 

Structure-activity studies of glucocorticoids have been carried out mainly in animals and are not necessarily applicable to clinical efficacy in man. Relative activity and dose correlations for the clinically useful drugs are found in Table 33.2. 

It is found that from induced activity and dose rate considerations, stellite can be replaced by either Colmonoy-6 or Tribaloy-700. Based on fast reactor experience with colmonoy, colmonoy has been chosen. An approximate estimate of the shield requirement assuming a permissible dose rate of 100 mR/h have been worked out. In the following discussions, as the basic SS component itself becomes radioactive and requires shielding, reduction in shield thickness is with respect to the minimum shielding required for the SS component [5]. 

The setup of a monitoring programme is the result of an optimization process in which the availability of measurement resources, the relative importance of different exposure pathways, and the levels of activity and dose in relation to the regulatory constraints are taken into consideration. Once a monitoring programme has been implemented, it should be reviewed periodically to ensure that it continually fulfils the objectives. 

Fig. 9. Dose-activity and dose-lethality relationships of some metallocene complexes (1, II, V, Vlll, XIII, XTV) against fluid Ehrlich ascites tumor in mice. BW Surviving animals...

Shielding that is adequate for all foreseen variations in activity and dose rate should be provided. Adequate shielding should be provided for all sources of radiation in and around the reactor facility, including the sources identified in Section 3, as appropriate ... 

CEPRAGA, D.G., MENAPACE, E., VANOSSI, A., Problem dependent nuclear data libraries in activation and dose calculations for "RB-3" reactor decommissioning. A paper presented at the IAEA Advisory Group Meeting on Nuclear Data Requirements for Fission Reactor Decommissioning, Vienna, Austria, 7-11 September, 1992. 

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