Dose Rate and Fractionation

The modalities of exposure for which there are at least s(xne hiunan data include the part of the body exposed to radiation, the dose to an organ or tissue, tl e distribution of the dose over time (dose-rate and fractionation), and the radiation quality defined in terms of LET. 

With respect to the effects of dose rate and firactionation, there is little evidence on which to compare radiation and chemicals. Although the limited data for radiation imply that dose fractionation has no... 

Another dose concept is that of the collective dose. It is based on the assumption that cancer is induced by a stochastic single process, independently of the dose rate and the dose fractionation, and it imphes that the detriment is the same whether one person receives 20 Sv or 20 000 persons receive 1 mSv each. In both cases the collective dose is 20 man sieverts (man Sv) and there should be a 100% probability of one disease of cancer. The collective dose concept is often apphed to assess the effect of the natural radiation background. At an average level of 3mSv/y, 0.015% of the population should die each year due to natural radiation. As the frequency of deaths by cancer is about 0.2% per year, it is not possible to confirm the collective dose concept by epidemiological investigations. 

The primary coolant circuit loops were divided into 28 sections (cf, 10 or 11 sections in the BWR case) as shown in Fig. 39. Each section is characterized by an inlet and outlet temperature y, n, and a dose rates flow fraction linear flow velocity hydrodynamic diameter section length material of construction (SS =... 

Collier CG, Strong JC, Humphreys JA, et al. Carcinogenicity of radon/radon decay product inhalation in rats—effect of dose, dose rate and unattached fraction. Int JRadiatBiol2005 81(9) 631—47. 

The rate (mass/time) and fractional extent of drug absorption (mass/dose = fa) from the intestinal lumen in vivo at any time t is shown schematically in Eq. (2) [4] ... 

Figure 11. Variation of unattached fraction of potential alpha-energy and equilibrium factor according to a model of room aerosol behaviour and the effect on bronchial dose rate per unit radon gas concentration.

Lennernas s group at Uppsala has performed extensive studies to confirm the validity of this in vivo experimental set-up at assessing the rate and the extent of drug absorption. Recovery of PEG 4000 (a non-absorbable marker) is more than 95%, which indicates that the absorption barrier is intact. In addition, maintenance of functional viability of the mucosa during perfusion has been demonstrated by the rapid transmucosal transport of D-glucose and L-leucine. Estimation of absorption half-lives from the measured Pefr agree well with half-lives derived from oral dose studies in humans (i.e. physiologically realistic half-lives). Human Peff estimates are well correlated with the fraction absorbed in humans, and served as the basis for BCS development, and hence the technique is ultimately the benchmark by which other in situ intestinal perfusion techniques are compared. The model has been extensively used to... 

BioavaUabUity and bioequivalence are related terms but they can be confused. Bioavailabihty as defined earlier is also known as absolute bioavailability and is simply the fraction of the administered dose that reaches the systemic circulation it is therefore defined only in terms of the extent of drug absorption. However, in the Committee for Proprietory Medicinal Products (CPMP) guideline for the investigation of bioavailability and bioequivalence, the former is defined as the rate and extent to which the active substance of therapeutic moiety is absorbed from a pharmaceutical form and becomes available at the site of action. The reason that bioavailability has been defined in this way is because rate, as well as extent, is important when comparing the bioavailability of two pharmaceutical forms of an active substance to determine whether they are bioequivalent. Bioequivalence and comparative bioavaUabUity are discussed later but absolute bioavailabihty will be described first. 

Available data indicate that 2-hexanone is readily absorbed by humans and various animal species after inhalation, oral, or dermal administration (Di Vencenzo et al. 1977, 1978). However, information on the rates of absorption via the inhalation and oral routes, as well as estimates of the fraction of the applied dermal dose that is absorbed, would be useful in assessing potential absorption by exposed humans. In addition, information on potential determinants of absorption such as dose level and nutritional status would also be helpful. 

LDPE/EVA blend was irradiated using gamma-irradiation and then expanded by heat as a foamed material. The EVA content in the blend was optimised to form a gel. The effects of atmospheres and of irradiation dose rate were studied. The ETIR spectra of the foam revealed the oxidation level. The relations between gel fraction of LDPE/EVA blend, expansion ratio, apparent density, average cell diameter and tensile properties of the foam are discussed. 8 refs. 

The initial combination modality clinical studies with cisplatin and fractionated radiation therapy was carried out in head and neck cancer with weekly cisplatin (120-160 mg/m2) and conventional single daily fraction radiation (95). In a follow-up intergroup study, patients were randomized to radiation therapy alone or to radiation therapy plus 20 mg/ m2/wk cisplatin (96). Both studies showed no major increase in normal tissue toxicity in the radiation field and showed an increase in response rate. There was no increase in complete response rate or in survival. Bachaud et al.(97) carried out a randomized study comparing radiation therapy alone with concurrent cisplatin (50 mg/m2) and radiation therapy in postoperative patients. This trial produced a significant reduction in local recurrence and improved disease-free survival with 59% of the patients receiving the full planned dose of cisplatin. 

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