Dose determination

The dose and dose rate of irradiation are important factors in any radiation grafting system. In the direct method the total dose determines the number of grafting sites, while the dose rate determines the number of grafting sites, and the dose rate determines the length of the grafted branches. The length of the branches is also con-... 

Ms. dimes, an 80-year-old woman, is receiving a lower dose of Demerol, a narcotic analgesic, postoperatively for pain. Her family questions the use of a lower dose Determine what information you would give her family when they voice concerns that the dosage will not adequately relieve their mother s pain. Analyze what... 

The performance should be evaluated in terms of drug and component physical and chemical compatibilities. Particle size and emitted dose determinations are required. Through-life performance should be evaluated as this is a multidosing reservoir system. The influence of temperature and humidity on stability and performance of the product should also be considered. 

Figure 34 Left (a) equilibrium storage modulus G as a function of y-irradiation dose determined from DMA experiments on exposed PU samples (b) 1/T2ave as a function of G. Right BC CPMAS NMR measurements on non-irradiated PU sample (a) 3 ms, (b) 0.5 ms, and (c) 100 pis. SS denotes soft segment HS denotes hard segment. Reprinted from Maxwell [87], Copyright 2003, with permission from Elsevier.

Acknowledging the possible existence of deviations, this simplified approach of using C and t for dose determination provides that basis for dose-response assessments in practically all inhalation toxicological studies. 

Maximum tolerated dose (determined by 5-day toxicity tests in non-tumor-bearing mice). 

The T25 value may either be incidentally obtained from the experimental smdy or calculated from other mmor incidences at the selected tumorigenic dose (determined above), using linear extrapolation, i.e., by multiphcahon of the dose with the factor 25/p where p is the acmal mmor incidence (e.g., in case of a net 15% incidence, multiply by 25/15). 

Dose determined by the type and severity of infection and susceptibility of the causative organism. 

Postoperative urine retention, atony of bladder PO 10-50 mg 3-4 times a day Minimum effective dose determined by giving 5-10 mg initially then repeating same amount at 1-hr intervals until desired response is achieved. Subcutaneous Initially 2.5-5 mg. Minimum effective dose determined by giving 2.5 mg (0.5 ml), repeating same amount at 15- to 30-min intervals up to a maximum of 4 doses. Minimum dose repeated 3-4 times a day. 

Total IgE levels are elevated during treatment and remain elevated for up to 1 yr after the discontinuation of treatment re-testing of IgE levels during omalizumab treatment cannot be used as a guide for dose determination dose determination after treatment interruptions last ing < 1 yr should be based on serum IgE levels obtained at the initial dose determination... 

When epidemiological data are available, the issues to be dealt with include selection of the appropriate study and control populations, evaluation of exposure levels and tissue doses, determination of the reliability of cancer ascertainment, allowance for the latent period and age distribution of cancers, control of biases and confounding factors, fitting of models to the data to characterize the dose-incidence relationship, and derivation of risk estimates with their associated ranges of uncertainty. 

One must he careful in dose determination because excessive doses of iodine cun produce harmful effects. 

Pharmacokinetics is defined as the study of the quantitative relationship between administered doses of a drug and the observed plasma/blood or tissue concentrations. The field of pharmacokinetics is concerned with drug absorption, distribution, biotransformation, and excretion or elimination. These processes, in addition to the dose, determine the concentration of drug at the effector or active site and, therefore, the intensity and duration of drug effect. 

Therapeutic dose determination based on the therapeutic index and effective dose required to mitigate the targeted disease state. 

If it is assumed that the radiation sterilizer equipment and facilities have been qualified and microbiological studies have been conducted as previously outlined, the next step in the validation process is the complete evaluation of the radiation sterilization cycle. Tests are conducted to determine the effect of minimum and maximum product density on the ability of the minimum or nominal radiation dose—determined during the microbiological studies to produce a given log reduction in the biological indicator population—to sterilize the load. For example, it was found that a 0.2-Mrad dose of cobalt-60 will produce a 1-log reduction in the population of B. pumilus. The microbial load of a one-package polyvinyl chloride (PVC) device (intravenous administration site) was estimated to be approximately 1000. A probability of a nonsterility level of 10 6 is desired, therefore theoretically, the minimum dose necessary to produce a 9-log reduction in the microbial population is 1.8 Mrad. 

An additional consideration is noteworthy when comparing acute and chronic toxicity. All chemicals elicit acute toxicity at a sufficiently high dose, whereas all chemicals do not elicit chronic toxicity. Paracelsus often cited phrase all things are poison. .. the dose determines. .. a poison is clearly in reference to acute toxicity. Even the most benign substances will elicit acute toxicity if administered at a sufficiently high dose. However, raising the dose of a chemical does not ensure that chronic toxicity will ultimately be attained. Since chronic toxicity typically occurs at dosages below those... 

Figure 24.3 Benchmark dose determination from dose response relationship with the BMDL corresponding to the lower end of a one-sided 95% confidence interval for the BMD.

Male Sprague-Dawley rats weighing 180-240 g are fed a commercial laboratory with low concentrations of thyroid hormones, containing constant amount of unlabelled iodine. The animals are treated for at least seven days with the test compound to be evaluated, at a pharmacologically active dose determined by a previous biological studies. On the morning of the test day, rats are injected with a test dose of 131-1 (intravenously or intraperitoneally), and the concentration of radioactivity in the thyroid glands is measured after 1 1 hours. The blood concentration of 131-1 at these time points is measured, and the tissue to blood ratios are calculated for individual animals. 

As a first step in the risk assessment of chemicals, it is essential to have an insight into the magnitude and duration of exposure. Following the toxicological principle that dose determines the effect, one may assume that no exposure means no risk. In the case of chemical mixtures, a proper assessment of exposure assists in adequately interpreting the interacting effects of chemicals. So, exposure assessment is an essential component of any risk assessment study of mixtures, since it can be used to reduce uncertainty and provide data. 

The effects of decreased renal function on drug elimination have been examined most extensively. This is appropriate, since only elimination clearance (CLe) and drug dose determine the steady-state concentration of drug in the body (Css). This is true whether the drug is given by constant intravenous infusion (J), in which case ... 

In a prospective double-blind study of more than 600 patients, 0.6 mg/kg of DAMB was compared with 3.0 mg/kg of L-Amb, a dose relation at the lower limit of equivalent doses determined in an animal model (117). At these dosages, in a large prospective double-blind study, there was a doubling of serum creatinine concentration in 19% of neutropenic patients receiving empirical therapy with L-AmB and 34% receiving conventional amphotericin (47). 

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