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1.
J Environ Radioact ; 101(1): 8-15, 2010 Jan.
Article de Anglais | MEDLINE | ID: mdl-19783331

RÉSUMÉ

Within the project "Environmental Modelling for Radiation Safety" (EMRAS) organized by the IAEA in 2003 experimental data of (131)I measurements following the Chernobyl accident in the Plavsk district of Tula region, Russia were used to validate the calculations of some radioecological transfer models. Nine models participated in the inter-comparison. Levels of (137)Cs soil contamination in all the settlements and (131)I/(137)Cs isotopic ratios in the depositions in some locations were used as the main input information. 370 measurements of (131)I content in thyroid of townspeople and villagers, and 90 measurements of (131)I concentration in milk were used for validation of the model predictions. A remarkable improvement in models performance comparing with previous inter-comparison exercise was demonstrated. Predictions of the various models were within a factor of three relative to the observations, discrepancies between the estimates of average doses to thyroid produced by most participant not exceeded a factor of ten.


Sujet(s)
Accident nucléaire de Tchernobyl , Radio-isotopes de l'iode/analyse , Modèles chimiques , Contrôle des radiations/méthodes , Retombées radioactives/analyse , Glande thyroide/métabolisme , Animaux , Enfant , Enfant d'âge préscolaire , Relation dose-effet des rayonnements , Exposition environnementale/analyse , Humains , Radio-isotopes de l'iode/métabolisme , Lait/métabolisme , Poaceae/métabolisme , Russie , Polluants radioactifs du sol/analyse
2.
Appl Radiat Isot ; 66(11): 1730-5, 2008 Nov.
Article de Anglais | MEDLINE | ID: mdl-18541435

RÉSUMÉ

The studies undertaken by the (131)I Working Group, part of the International Atomic Energy Agency's EMRAS (Environmental Modelling for Radiation Safety) programme, were focused primarily on evaluating the predictive capability of environmental models. Particular emphasis was placed on applying models to evaluate the effectiveness of countermeasures.


Sujet(s)
Accident nucléaire de Tchernobyl , Radio-isotopes de l'iode/analyse , Radio-isotopes de l'iode/pharmacocinétique , Modèles biologiques , Contrôle des radiations/méthodes , Retombées radioactives/analyse , Retombées radioactives/prévention et contrôle , Animaux , Charge corporelle , Simulation numérique , Europe , Humains , Dose de rayonnement , Reproductibilité des résultats , Sensibilité et spécificité
3.
Appl Radiat Isot ; 66(11): 1558-60, 2008 Nov.
Article de Anglais | MEDLINE | ID: mdl-18485719

RÉSUMÉ

In relation to the management of elevated discharges of radioactive materials from the Paks Nuclear Power Plant, two different types of notification level are proposed. They relate to discharges which are above normal but below those associated with an emergency. The first is technically based (reference level) while the second (reporting level) is mainly based on considerations of public concern. The actions expected to be implemented if either of the levels is exceeded are summarized.


Sujet(s)
Exposition environnementale/analyse , Diffusion de l'information/méthodes , Déclaration obligatoire , Contrôle des radiations/normes , Radioprotection/normes , Émission de source de risque radioactif/prévention et contrôle , Radio-isotopes/analyse , Gestion de la sécurité/normes , Charge corporelle , Prévision , Réglementation gouvernementale , Recommandations comme sujet , Hongrie , Internationalité , Contrôle des radiations/législation et jurisprudence , Contrôle des radiations/méthodes , Radioprotection/législation et jurisprudence , Émission de source de risque radioactif/législation et jurisprudence , Normes de référence , Appréciation des risques/législation et jurisprudence , Appréciation des risques/normes , Appréciation des risques/tendances , Gestion de la sécurité/législation et jurisprudence , Gestion de la sécurité/tendances
4.
J Radiol Prot ; 26(2): 161-87, 2006 Jun.
Article de Anglais | MEDLINE | ID: mdl-16738414

RÉSUMÉ

The BIOMOSA (BIOsphere MOdels for Safety Assessment of radioactive waste disposal) project was part of the EC fifth framework research programme. The main goal of this project was to improve the scientific basis for the application of biosphere models in the framework of long-term safety studies of radioactive waste disposal facilities and to enhance the confidence in using biosphere models for performance assessments. The study focused on the development and application of a generic biosphere tool BIOGEM (BIOsphere GEneric Model) using the IAEA BIOMASS reference biosphere methodology, and the comparison between BIOGEM and five site-specific biosphere models. The site-specific models and the generic model were applied to five typical locations in Europe, resulting in estimates of the annual effective individual doses to the critical groups and the ranking of the importance of the exposure pathways for each of the sites. Uncertainty in the results was also estimated by means of stochastic calculations based on variation of the site-specific parameter values. This paper describes the generic model and the deterministic and stochastic results obtained when it was applied to the five sites. Details of the site-specific models and the corresponding results are described in two companion papers. This paper also presents a comparison of the results between the generic model and site-specific models. In general, there was an acceptable agreement of the BIOGEM for both the deterministic and stochastic results with the results from the site-specific models.


Sujet(s)
Écosystème , Modèles biologiques , Contrôle des radiations/méthodes , Polluants radioactifs/analyse , Appréciation des risques/méthodes , Charge corporelle , Simulation numérique , Europe , Dose de rayonnement , Efficacité biologique relative , Facteurs de risque
5.
J Radiol Prot ; 25(4): 375-91, 2005 Dec.
Article de Anglais | MEDLINE | ID: mdl-16340067

RÉSUMÉ

In the framework of the BioMoSA project for the development of biosphere assessment models for radioactive waste disposal the Reference Biosphere Methodology developed in the IAEA programme BIOMASS was applied to five locations, situated in different European countries. Specific biosphere models were applied to assess the hypothetical contamination of a range of agricultural and environmental pathways and the dose to individuals, following contamination of well water. The results of these site-specific models developed by the different BioMoSA partners, and the individual normalised dose to the exposure groups were compared against each other. Ingestion of drinking water, fruit and vegetables were found to be among the most important pathways for almost all radionuclides. Stochastic calculations revealed that consumption habits, transfer factors, irrigation rates and distribution coefficients (Kd(s)) were the most important parameters that influence the end results. Variations in the confidence intervals were found to be higher for sorbing elements (e.g. (36)Cl, (237)Np, (99)Tc, (238)U, (129)I) than for mobile elements (e.g. (226)Ra, (79)Se, (135)Cs, (231)Pa, (239)Pu). The influence of daughter products, for which the distribution into the biosphere was calculated individually, was also shown to be important. This paper gives a brief overview of the deterministic and stochastic modelling results and the parameter sensitivity. A screening methodology was introduced to identify the most important pathways, simplify a generic biosphere tool and refine the existing models.


Sujet(s)
Modèles théoriques , Déchets radioactifs , Radiométrie/méthodes , Élimination des déchets/méthodes , Polluants radioactifs de l'eau/analyse , Alimentation en eau , Adulte , Exposition environnementale , Europe , Humains , Nourrisson , Méthode de Monte Carlo , Élimination des déchets/normes , Appréciation des risques
6.
J Radiol Prot ; 25(4): 343-73, 2005 Dec.
Article de Anglais | MEDLINE | ID: mdl-16352869

RÉSUMÉ

This paper describes the development and application of site-specific biosphere models that might be used for assessment of potential exposures in the framework of performance assessment studies of nuclear waste disposals. Model development follows the Reference Biosphere Methodology that has been set up in the framework of the BIOMASS study. In this paper, the application is to real sites at five European locations for which environmental and agricultural conditions have been described and characterised. For each of the sites a biosphere model has been developed specifically assuming a release of radionuclides to waters that are used by humans, for example as drinking water for humans and cattle and as irrigation water. Among the ingestion pathways, the intakes of drinking water, cereals, leafy vegetables, potatoes, milk, beef and freshwater fish are included in all models. Annual individual doses were calculated, and uncertainties in the results were estimated by means of stochastic calculations. To enable a comparison, all results were normalised to an activity concentration in groundwater of 1 Bq m(-3) for each of the radionuclides considered ((36)Cl, (79)Se, (99)Tc, (129)I, (135)Cs, (226)Ra, (231)Pa, (230)Th, (237)Np, (239)Pu, and (238)U), i.e. those that are usually most relevant in performance assessment studies of nuclear waste disposals. Although the results do not give answers in absolute terms on potential future exposures, they indicate the spectrum of exposures that might occur in different environments and specify the interaction of environmental conditions, human habits and potential exposure.


Sujet(s)
Exposition environnementale/normes , Déchets radioactifs , Radiométrie/méthodes , Élimination des déchets/méthodes , Animaux , Europe , Contamination des aliments/prévention et contrôle , Humains , Appréciation des risques , Polluants radioactifs du sol/normes , Pollution radioactive de l'eau
7.
J Environ Radioact ; 84(2): 225-44, 2005.
Article de Anglais | MEDLINE | ID: mdl-15990206

RÉSUMÉ

Data collected for 10 years following the Chernobyl accident in 1986 have provided a unique opportunity to test the reliability of computer models for contamination of terrestrial and aquatic environments. The Iput River scenario was used by the Dose Reconstruction Working Group of the BIOMASS (Biosphere Modelling and Assessment Methods) programme. The test area was one of the most highly contaminated areas in Russia following the accident, with an average contamination density of 137Cs of 800,000 Bq m-2 and localized contamination up to 1,500,000 Bq m-2, and a variety of countermeasures that were implemented in the test area had to be considered in the modelling exercise. Difficulties encountered during the exercise included averaging of data to account for uneven contamination of the test area, simulating the downward migration and changes in bioavailability of 137Cs in soil, and modelling the effectiveness of countermeasures. The accuracy of model predictions is dependent at least in part on the experience and judgment of the participant in interpretation of input information, selection of parameter values, and treatment of uncertainties.


Sujet(s)
Centrales énergétiques , Émission de source de risque radioactif , Polluants radioactifs de l'eau , Radio-isotopes du césium , Russie , Ukraine
8.
J Environ Radioact ; 84(2): 211-24, 2005.
Article de Anglais | MEDLINE | ID: mdl-15975695

RÉSUMÉ

The Hanford test scenario described an accidental release of 131I to the environment from the Hanford Purex Chemical Separations Plant in September 1963. Based on monitoring data collected after the release, this scenario was used by the Dose Reconstruction Working Group of BIOMASS to test models typically used in dose reconstructions. The primary exposure pathway in terms of contribution to human doses was ingestion of contaminated milk and vegetables. Predicted mean doses to the thyroid of reference individuals from ingestion of 131I ranged from 0.0001 to 0.8 mSv. For one location, predicted doses to the thyroids of two children with high milk consumption ranged from 0.006 to 2 mSv. The predicted deposition at any given location varied among participants by a factor of 5-80. The exercise provided an opportunity for comparison of assessment methods and conceptual approaches, testing model predictions against measurements, and identifying the most important contributors to uncertainty in the assessment result. Key factors affecting predictions included the approach to handling incomplete data, interpretation of input information, selection of parameter values, adjustment of models for site-specific conditions, and treatment of uncertainties.


Sujet(s)
Radio-isotopes de l'iode , Centrales énergétiques , Modèles théoriques , Washington
9.
J Environ Radioact ; 79(2): 223-30, 2005.
Article de Anglais | MEDLINE | ID: mdl-15603909

RÉSUMÉ

The inhalation dose due to radon and its progenies could be averted by ventilation in dwellings; however, on the other hand the increased ventilation augments the heating cost. Therefore a cost-benefit analysis could contribute to optimise the ventilation rate. In our current work we applied our former defined parameters of the optimising procedure to assess the optimised ventilation and radon concentration in dwellings with average parameters. To assess the inhalation dose rates the time-dependent concentrations of all the progenies were calculated in case of periodic and continuous ventilation as well, at three different radon entry rates (5, 10, 20kBqh(-1)). The optimal ventilation rates in case of continuous ventilation are 0.22, 0.40 and 0.66h(-1), respectively. By these conditions the optimal radon concentration takes 160-210Bqm(-3). According to the more detailed analysis the periodic ventilation gives, in general, a better solution than the continuous one. The Monte Carlo simulations provided a large uncertainty; therefore, before the practical application of the results the uncertainty should be decreased taken into account the local conditions.


Sujet(s)
Polluants atmosphériques radioactifs/analyse , Pollution de l'air intérieur , Logement , Radon/analyse , Ventilation , Polluants atmosphériques radioactifs/effets indésirables , Coûts et analyse des coûts , Radioprotection (spécialité) , Humains , Cinétique , Méthode de Monte Carlo , Dose de rayonnement , Radon/effets indésirables
10.
J Environ Radioact ; 62(3): 235-40, 2002.
Article de Anglais | MEDLINE | ID: mdl-12164629

RÉSUMÉ

Concentration of the radionuclide 226Ra was determined in almost every type of bottled mineral water commercially available in Hungary. Determination of the radon coming from the radium dissolved in the water was used for activity measurement. As the results show, the 226Ra concentrations exceed the level of 100 mBq l(-1) in six cases out of the 28 types of mineral water investigated. In one case 3 Bq l(-1) was measured, which provides 0.3 mSv year(-1) committed effective dose for adults in the case of a consumption rate of 1 l day(-1). In soft drinks produced from mineral water a concentration of 2.6 Bq l(-1) was determined, which means 1.4 mSv year(-1) effective dose in the age group 12-17 years in the case of permanent daily drinking of 1 l of these beverages.


Sujet(s)
Boissons , Exposition environnementale , Contamination radioactive des aliments , Eau minérale , Radon/analyse , Polluants radioactifs de l'eau/analyse , Adolescent , Adulte , Enfant , Humains , Hongrie
11.
J Environ Radioact ; 61(3): 319-29, 2002.
Article de Anglais | MEDLINE | ID: mdl-14689995

RÉSUMÉ

The paper presents results on model validation by field experiment for transport of 134Cs to strawberry. The transfer of 134Cs to herbaceous plants was investigated following a wet deposition after an acute release during 2000. Leaf-to-fruit, soil-to-fruit and direct fruit pathways were examined. The available meteorological and local soil information together with the experimental data were taken into account by the model RUVFRU. The processes are described by first order differential equations. In the case of foliar contamination scenarios measured and calculated results for fruit are in good agreement. However, the results of soil contamination scenarios provide large differences of up to three orders of magnitude between model predictions and experimental values for either fruit or other parts of the plant. The bias could be explained by the underestimation of the interception of the plant at the beginning of the season, in the soil contamination scenario. The model output permits prompt assessment of emergency situations and provides aid making decisions concerning mitigation of the consequences of the accident.


Sujet(s)
Césium/pharmacocinétique , Fragaria/composition chimique , Polluants radioactifs du sol/pharmacocinétique , Radio-isotopes du césium/pharmacocinétique , Fruit/composition chimique , Concepts météorologiques
12.
Health Phys ; 80(2): 137-41, 2001 Feb.
Article de Anglais | MEDLINE | ID: mdl-11197460

RÉSUMÉ

The monetary value of the averted dose is a key element in the implementation of the optimization principle both in radiation praxis and intervention. The main concept of this principle is to select options so as to maintain exposures at a reasonable level. The feature of this concept is to look for the minimal total cost, i.e., the sum of the costs of protection and health detriment. In its publications, ICRP emphasized the need for developing models which also take into account the "subjective" aspects of health detriment in the optimization process, such as the perception of risk by individuals and the need to put more emphasis on equity in the distribution of individual doses. This paper proposes a modified alpha-value model based on CEPN's model (Centre d'Etude sur L'Evaluation de la Protection dans le Domaine Nucleaire) to put more emphasis on recently published considerations about the smaller effects of the portion of collective dose derived from small doses. The parameters of the monetary value of unit collective dose averted, which is a key element of this type of model, can be estimated by means of approaches like human capital (HC) and willingness to pay (WTP) from the point of view of economic theories. The present study summarizes the results achieved by WTP among the radiation specialists mainly from the Paks Nuclear Power Plant, Hungary. The aim of the effort was to determine the value of a statistical life and the monetary value of a unit person-sievert associated with averted occupational exposure due to ionizing radiation. To apply the WTP method, a questionnaire has been prepared on the basis of the one introduced by CEPN in the late 1990's. The investigations show that the value of US$6,200 person-Sv(-1) seems to be acceptable for the alphabase-value for the occupational situation in Hungary in 1999. WTP assessments should be applied with caution since the economic level of the country, the workplace surveyed, and the computational methods affect the results. In addition, achieving a high level safety culture must rely on international cooperation both from the theoretical and practical viewpoints, and international markets affect the associated costs. Therefore the monetary requirements cannot always be assessed solely on a national basis.


Sujet(s)
Modèles économiques , Contrôle des radiations , Radioprotection , Analyse coût-bénéfice , Coûts et analyse des coûts , France , Humains , Hongrie , Contrôle des radiations/économie , Contrôle des radiations/législation et jurisprudence , Radioprotection/économie , Radioprotection/législation et jurisprudence , Appréciation des risques , États-Unis
13.
Health Phys ; 75(6): 648-51, 1998 Dec.
Article de Anglais | MEDLINE | ID: mdl-9827513

RÉSUMÉ

High concentrations of 226Ra (865-2,383 Bq kg(1)) were measured in the coal-slags, originated from the region of the settlement Tatabánya, Transdanubian Middle Mountains, Hungary. These slags are commonly used as building materials in this district. The external gamma dose rate was measured in 188 rooms at different heights above the floor. In 124 rooms with slags used for construction, the average absorbed dose rate was 296 nGy h(-1). In 10 apartments the average radon concentration was 502 Bq m(-3). In that case the estimated effective dose due to inhaled radon and its progeny and gamma radiation was 10.3 mSv y(-1).


Sujet(s)
Charbon/analyse , Matériaux de construction , Rayons gamma , Logement/normes , Radon/analyse , Industrie minière charbon , Humains , Hongrie , Santé en zone urbaine
14.
Health Phys ; 66(4): 420-6, 1994 Apr.
Article de Anglais | MEDLINE | ID: mdl-8138408

RÉSUMÉ

The transfer coefficient of 110mAg to a range of sheep tissues and its biological half-life in these tissues has been determined. Liver was shown to be the major site of 110mAg deposition and retention, with a transfer coefficient of Ff 7.1 d kg-1 and a biological half-life of 79 d. These results also suggest that previous estimates of the transfer of silver to muscle were too high, although further work would be required to confirm this. There is a need for accurate data which can be used to predict the transfer of 110mAg to food-producing animals.


Sujet(s)
Radio-isotopes/pharmacocinétique , Ovis/métabolisme , Argent/pharmacocinétique , Animaux , Femelle , Distribution tissulaire
15.
Health Phys ; 57(4): 587-92, 1989 Oct.
Article de Anglais | MEDLINE | ID: mdl-2793474

RÉSUMÉ

Transfer coefficients for 137Cs from the Chernobyl accident were determined for milk (Fm) and meat (Ff) of cows and sheep in Hungary. Fm and Ff for both cows and sheep fed forage harvested within 1 mo of the accident were lower than results reported for worldwide fallout from weapons tests. Forage harvested 60 d or later after the accident produced an Fm similar to results from feeding soluble 134Cs. The results are interpreted to indicate three distinct categories of Fm about 2.0 X 10(-3), 4.0 X 10(-3) and 1.4 X 10(-2) d L-1, respectively, for Chernobyl fallout, worldwide fallout and soluble Cs isotopes or 137Cs contained in plants from soil uptake.


Sujet(s)
Accidents , Radio-isotopes du césium/analyse , Viande/analyse , Lait/analyse , Réacteurs nucléaires , Animaux , Bovins , Contamination radioactive des aliments , Hongrie , Retombées radioactives/analyse , Ovis , Ukraine
16.
Cancer Chemother Pharmacol ; 22(2): 104-8, 1988.
Article de Anglais | MEDLINE | ID: mdl-3136940

RÉSUMÉ

The pharmacokinetics of mitomycin (MMC) was studied in Wistar rats. Up to five half-lives, the plasma concentration-time curve was biphasic. The AUC changed linearly with increasing doses between 0.5 and 7.5 mg/kg, which corresponds to 0.2 and 3 times the LD50 value in rats. Most of the drug was metabolized, and only 1%-2% and 10%-15% of the dose was eliminated unchanged by biliary and urinary excretion, respectively. The AUC of MMC at the LD50 is slightly less than that reported for the human MTD. Inoculation of MMC together with 5-fluorouracil and doxorubicin did not change the terminal half-life of MMC but decreased the total body clearance and the volume of distribution. The lack of significant influence of phenobarbital and 3-methylcholanthrene pretreatment on the terminal elimination half-life suggests that microsomal drug-metabolizing enzymes inducible by these compounds do not play a decisive role in the in vivo biotransformation of MMC.


Sujet(s)
Microsomes du foie/effets des médicaments et des substances chimiques , Mitomycines/pharmacocinétique , Animaux , Interactions médicamenteuses , Période , Mâle , 1,2-Dihydro-méthyl-benzo[j]acéanthrylène/pharmacologie , Microsomes du foie/métabolisme , Mitomycine , Mitomycines/administration et posologie , Mitomycines/toxicité , Phénobarbital/pharmacologie , Rats , Lignées consanguines de rats
17.
Cancer Chemother Pharmacol ; 22(2): 109-13, 1988.
Article de Anglais | MEDLINE | ID: mdl-3409440

RÉSUMÉ

The pharmacokinetics of diacetyldianhydrogalactitol (DADAG) was compared in mice, rats, and humans. The ratios of human therapeutic dose (ThD) to the LD10 were 8 and 5 in mice and rats, respectively. The ratios of the corresponding AUCs of DADAG were 20 and 17, whereas those of dianhydrogalactitol (DAG), the main, active metabolite of DADAG, were 8 in both species. The lower human-to-rodent ratio for DAG was due to the fact that twice as much DAG was formed in the animals. Other factors contributing to the larger AUC in man were the 3-5 times smaller distribution volume found in humans as well as the lower hexitol sensitivity of human bone marrow cells. We conclude that in addition to the distance between the AUCs of the LD10 and of the human starting dose, interspecies pharmacokinetic differences should also be considered in planning the rate of dose escalation.


Sujet(s)
Dianhydro-galactitol/pharmacocinétique , Polyols/pharmacocinétique , Algorithmes , Animaux , Dianhydro-galactitol/administration et posologie , Dianhydro-galactitol/analogues et dérivés , Femelle , Humains , Mâle , Souris , Souris de lignée BALB C , Souris de lignée CBA , Rats , Lignées consanguines de rats
18.
Eur J Cancer Clin Oncol ; 22(2): 163-71, 1986 Feb.
Article de Anglais | MEDLINE | ID: mdl-3699079

RÉSUMÉ

Dianhydrogalactitol (DAG), labelled with 3H, was administered in single intravenous or oral doses to six patients (three in each group) with cancer. Kinetic parameters were calculated for the unchanged DAG and its biotransformation products. Elimination of the drug by metabolism and excretion was described by a catenary model. In order to elucidate the role of DAG as a mediator of the alkylating action of the cytostatic drug dibromodulcitol (DBD), the pharmacokinetic parameters of DAG and DBD were compared. The mean residence time for pharmacologically active molecules in the body was six times shorter for DAG (1.9 hr) than for DBD (11.4 hr). Alkylating action and metabolic degradation proceeded about 8-9 times faster for DAG than for DBD. The process of DBD alkylation implies a slow solvolytic conversion of the parent drug into the more reactive bromoepoxide and DAG. The preformed DAG would be rapidly consumed by intracellular alkylation and degradation, while unchanged DBD could form a depot in the cells and exert its cytostatic activity through the epoxides released in situ by solvolytic activation. Thus DBD entering the cells in unchanged form may have a more important role in its therapeutic effects than had been assumed earlier.


Sujet(s)
Dianhydro-galactitol/métabolisme , Mitolactol/métabolisme , Tumeurs/métabolisme , Polyols/métabolisme , Adulte , Sujet âgé , Alkylation , Biotransformation , Dianhydro-galactitol/sang , Dianhydro-galactitol/urine , Femelle , Humains , Cinétique , Mâle , Adulte d'âge moyen , Modèles biologiques , Tumeurs/sang , Tumeurs/urine , Épanchement pleural/métabolisme , Liaison aux protéines
19.
Cancer Chemother Pharmacol ; 16(3): 257-63, 1986.
Article de Anglais | MEDLINE | ID: mdl-3698167

RÉSUMÉ

Diacetyldianhydrogalactitol (DADAG), a new alkylating hexitol derivative, was given in 30-min infusions for 5 consecutive days or as a single high-dose administration. The parent drug was eliminated in a biphasic manner, with a terminal half-life of 30-40 h. Dianhydrogalactitol (DAG), the main, pharmacologically active metabolite, appeared after a lag time of about 0.2-0.6 h. Its peak concentration was reached 1-2 h after termination of the infusion. The terminal elimination of DAG followed that of the parent compound. During the 5-day schedule slight accumulation was observed, and the plasma concentrations of both compounds approached the steady state. Over a dose range of 75-1050 mg/m2 the daily mean plasma concentrations of DADAG increased by only about 3-4 times. Dose-dependent expansions of the distribution volumes of the drug (Vc, V lambda, Vss) were observed. The behavior of DADAG and DAG in the body could be adequately described by a three-compartment open model. After equilibration the plasma levels of the parent compound and its metabolite were determined by the rate of return of DADAG from the peripheral compartment and its conversion to DAG.


Sujet(s)
Agents alcoylants/métabolisme , Antinéoplasiques/métabolisme , Dianhydro-galactitol/métabolisme , Polyols/métabolisme , Adulte , Dianhydro-galactitol/analogues et dérivés , Relation dose-effet des médicaments , Évaluation de médicament , Humains , Cinétique , Taux de clairance métabolique , Adulte d'âge moyen , Prednisolone/métabolisme , Liaison aux protéines
20.
Cancer Chemother Pharmacol ; 16(3): 264-8, 1986.
Article de Anglais | MEDLINE | ID: mdl-3698168

RÉSUMÉ

Diacetyldianhydrogalactitol (DADAG), a new alkylating sugar alcohol derivative, was administered as single, 30-min infusions in doses ranging from 390 to 1200 mg/m2. The dose-limiting toxicity was myelosuppression. The median times to WBC nadir and regeneration were 16 and 21 days, and to platelet nadir and recovery 20 and 27, respectively. Nausea and vomiting occurred frequently and were of moderate severity. For phase II studies 900 mg/m2 DADAG given every 4-6 weeks is recommended. The area under the plasma concentration time curve (AUC) for DADAG did not increase in proportion with dose escalation; it changed only from 235.5 +/- 70.7 to 262.4 +/- 71.5 micrograms h ml-1 between doses of 690 and 1050 mg/m2. No correlations between the dose administered and the nadir values for haemoglobin concentration, WBC and platelet counts, or the number of episodes of vomiting were demonstrable in this dose range. Such an association was revealed, however, when the above biological variables were related to the individual AUC for DADAG.


Sujet(s)
Antimétabolites/toxicité , Antinéoplasiques/toxicité , Dianhydro-galactitol/toxicité , Polyols/toxicité , Adulte , Sujet âgé , Antimétabolites/sang , Antinéoplasiques/sang , Dianhydro-galactitol/analogues et dérivés , Dianhydro-galactitol/sang , Relation dose-effet des médicaments , Évaluation de médicament , Femelle , Cellules souches hématopoïétiques/effets des médicaments et des substances chimiques , Humains , Numération des leucocytes , Mâle , Adulte d'âge moyen , Numération des plaquettes , Vomissement/induit chimiquement
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