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Biomedical subjects

A Rescigno

Publications and source records attributed to A Rescigno.

16 recordsLinked to original sources

Bioequivalence.

The bioequivalence of two formulations of the same drug may be determined by evaluating the similarity of their respective plasma concentration curves. The similarity of two plasma concentration functions can be measured by an index called the bioequivalence index. This paper shows how such an index may be defined and calculated.

Chemistry, Pharmaceutical

Estimation of permanence time, exit time, dilution factor, and steady-state volume of distribution.

General solutions for exist time, permanence time, dilution factor, and volume of distribution at steady state are derived for compartmental and noncompartmental systems. These derivations require that the systems are linear and state-determined. Unique values for these parameters cannot be determined when the site of elimination is not known; in this case the parameters can be defined by a range. Interpretation of this range and its significance and use in clinical situations are illustrated with two examples.

Mathematics

Olive milling wastewater as a medium for growth of four Pleurotus species.

Four species of Pleurotus were adapted to grow on olive milling wastewater, and in certain conditions produced high yield of fruit bodies. Some biochemical transformations were observed in the olive milling wastewater owing to the growth of Pleurotus. In particular, the fungi actively excreted large amounts of laccase in the medium, and at the same time the concentration of phenolics and other toxic compounds significantly decreased, as revealed by HPLC analysis and toxicity tests on standard cultures of human cell lines.

Culture Media

Pharmacokinetics in patients of an anti-carcinoembryonic antigen antibody radiolabeled with indium-111 using a novel diethylenetriamine pentaacetic acid chelator.

The pharmacokinetics of the C110 anti-carcinoembryonic antigen antibody radiolabeled with 111In via a novel benzylisothiocyanate derivative of diethylenetriamine pentaacetic acid have been determined in 12 patients. The chelator was attached to the protein via a thiourea bond and in such a way that all 5 carboxymethyl arms were presumably able to participate in chelation. Patients with known or suspected colorectal carcinoma received between 5 and 20 mg of the IgG antibody labeled with 5 mCi of 111In. Individual organ radioactivity levels were quantitated, and serum and urine samples were analyzed, principally by size exclusion high-performance liquid chromatography (HPLC). Total urinary excretion averaged 0.18% of the injected dose/h with large patient to patient variation. At early times postadministration (less than 8 h) the predominant radiolabeled species in urine was free diethylenetriamine pentaacetic acid most probably administered as a small radiocontaminant in the injectate. Thereafter, radioactivity in urine was primarily present as a low molecular weight catabolic product. Analysis of serum by size exclusion HPLC occasionally showed 3 radioactivity peaks, 2 of which are due to circulating immune complexes and labeled antibody. The third peak is of low molecular weight and is due to one or more products of antibody catabolism. Transchelation of 111In to circulating transferrin was observed but at modest levels. Quantitation of organ radioactivity showed that 18 +/- 4 (SD)% of the injected dose was in the liver at 1 day postadministration and 1.4 +/- 1.1 and 1.2 +/- 0.9% was in the spleen and in both kidneys, respectively, at this time. The mean half-life for clearance of total injected radioactivity was fitted to a single exponential and was found to be 34 h (SD, 14 h; N = 13) and that for antibody alone, assessed by size exclusion HPLC analysis of serum samples, was calculated to be 22 h (SD, 8 h; N = 10). Neither of these values nor organ radioactivity levels were affected by antibody-loading dose.

Adult

Pharmacokinetic modeling of radiolabeled antibody distribution in man.

This paper describes a method for the interpretation of the pharmacokinetics in cancer patients of an anti-CEA monoclonal antibody labeled with 111In. To determine the fate of the radiolabeled antibody administered i.v. to ten colon patients, the radioactivity contained in liver, spleen, kidneys, bone marrow, and tumor was measured and serum samples were counted. In addition each serum and urine sample was also analyzed by HPLC. The labeled antibody and two other radioactive species were observed in serum: an immunocomplex and a catabolic product. The computer program SAAM was used to fit the data. Thus, the rate constants for a number of pharmacokinetic models were calculated using the time-dependent serum radioactivity curves for each of the three species and the time-dependent radioactivity contained in normal organs. We also computed the model parameters for different connections between different organs, and using noncompartmental methods, the transit time, permanence time, and yield of those organs. Our results suggest that the immunocomplexes are formed in the circulation between circulating antibody and antigen, and that the rate of uptake by the liver depends on the concentration of the antibody in blood and not of the immunocomplex. Following deposition in the liver, free antibody does not appear to reenter the circulation, but once there it is catabolized. All breakdown products are then cleared into urine via serum.

Antibodies, Monoclonal