[Theory of statistical moments in pharmacokinetic studies: application to the bioavailability of propranolol].
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Biomedical subjects
Publications and source records attributed to L Lucchini.
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Fungal opportunistic infections are a danger for immunocompromised hosts, such as patients with malignancies, especially in a hospital environment. We studied a group of patients with solid tumors of the respiratory tract on admission and after twenty days of hospitalization. Colonization by moulds and/or yeasts was frequently found. Preventive measures should be applied to avoid colonization inside the hospital. The importance of overcrowding, sanitation and diet is pointed out.
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Eight normal male volunteers received 80 mg doses of propranolol by the oral and rectal routes and 2.2 mg by intravenous administration in a crossover fashion. Plasma concentrations of propranolol were measured by a gas chromatographic method using an electron capture detector. Individual subject concentration-time data were analysed and results indicated that the data fit a two compartment model with first order absorption. An approximately two-fold higher plasma propranolol concentration was observed after rectal administration as compared with oral dosing. Statistical analysis of the difference in the total AUCs indicates a significantly higher bioavailability of propranolol administered by the rectal route. The reduced bioavailability after oral administration indicates a substantial first pass effect but that it is possible to bypass the liver, at least partially, by giving the drug rectally to man.
The principal aims of the project financed by the Italian Ministry of University and Scientific and Technological Research were: to verify if at the current limit values early biological effects can be demonstrated; to identify the levels of internal dose that can cause early effects; to evaluate the non-occupational factors that can contribute to the levels of internal dose. In particular, the mercury intake derived from dental amalgams and fish consumption was considered. The internal dose was measured with the traditional biological indicators (urinary and blood mercury) and with the speciation of a large percentage of biological samples by ICP-MS. The central nervous system, neuroendocrine function, kidney and the immune system were considered as target organs and were examined using previously standardized indicators of effects. Two groups of subjects were included in the study: workers with occupational exposure to inorganic mercury in different industrial settings and control subjects identified from the general population. The first group was characterized by an exposure level to inorganic mercury clearly below the current limit values; whereas the HgU levels of a relevant number of control subjects were similar to those measured in the exposed subjects. The in vitro studies covered several issues: the percutaneous absorption of mercury using skin derived from human post-mortem samples in a standardized model; the release of the metal from dental amalgams in different physiological conditions of the oral cavity; the effects of increasing doses of mercury chloride on tubular renal cells. The project was realized with the cooperation of seven Research Units from six Italian Universities. Researchers belonging to Departments of Occupational Medicine, Industrial Hygiene, General Pathology, Biochemistry, Odontology, and Biostatistics were involved to achieve a multidisciplinary approach. The results of this research project are described and discussed in the following papers.
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