The Experts below are selected from a list of 183 Experts worldwide ranked by ideXlab platform
Elmar Richter - One of the best experts on this subject based on the ideXlab platform.
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Tissue distribution and excretion of myosmine after i.v. administration to Long–Evans rats using quantitative Whole-Body Autoradiography
Archives of Toxicology, 2007Co-Authors: Susanna Glas, Stefan Tyroller, Wolfgang Zwickenpflug, Kurt Steiner, Gudrun Kiefer, Elmar RichterAbstract:Occurrence of the tobacco alkaloid myosmine has been proven in various staple foods, vegetables and fruits. Myosmine can be easily activated by nitrosation yielding 4-hydroxy-1-(3-pyridyl)-butanone (HPB) and the esophageal carcinogen N ′-nitrosonornicotine. Most of the reaction products after myosmine peroxidation were also identified as urinary metabolites after oral administration to rats. Whole-Body Autoradiography with freeze dried or multiple solvent extracted tissue sections was used to trace [2′-^14C]myosmine (0.1 mCi/kg bw) 0.1, 0.25, 1, 4 and 24 h after i.v. injection in Long–Evans rats. In addition, in vitro binding of radioactivity to esophageal and eye tissue was determined and excretion of radioactivity via urine and feces was quantified. Radioactivity is rapidly eliminated by renal excretion. Approximately 30% of the administered radioactivity was recovered in urine within the first 4 h and excretion with urine (72%) and feces (15%) was nearly complete after 24 h. A rapid concentration of radioactivity can be seen in the stomach and in the salivary and lachrymal glands. Rats killed 1 and 4 h after treatment showed by far the highest labeling in the accessory genital gland. High levels of nonextractable radioactivity were present in esophageal tissue and melanin. The half lives for the disappearance of radioactivity from various tissues are in the order of about 1 h. Eye and esophagus sections both showed nonextractable labeling after in vitro incubation with ^14C-myosmine. In conclusion, the toxicological significance of myosmine accumulation in esophagus and accessory genital gland requires further investigations. Hair analysis might be applicable for myosmine biomonitoring, because of possible enrichment in melanin containing tissues.
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tissue distribution and excretion of myosmine after i v administration to long evans rats using quantitative Whole Body Autoradiography
Archives of Toxicology, 2007Co-Authors: Susanna Glas, Stefan Tyroller, Wolfgang Zwickenpflug, Kurt Steiner, Gudrun Kiefer, Elmar RichterAbstract:Occurrence of the tobacco alkaloid myosmine has been proven in various staple foods, vegetables and fruits. Myosmine can be easily activated by nitrosation yielding 4-hydroxy-1-(3-pyridyl)-butanone (HPB) and the esophageal carcinogen N′-nitrosonornicotine. Most of the reaction products after myosmine peroxidation were also identified as urinary metabolites after oral administration to rats. Whole-Body Autoradiography with freeze dried or multiple solvent extracted tissue sections was used to trace [2′-14C]myosmine (0.1 mCi/kg bw) 0.1, 0.25, 1, 4 and 24 h after i.v. injection in Long–Evans rats. In addition, in vitro binding of radioactivity to esophageal and eye tissue was determined and excretion of radioactivity via urine and feces was quantified. Radioactivity is rapidly eliminated by renal excretion. Approximately 30% of the administered radioactivity was recovered in urine within the first 4 h and excretion with urine (72%) and feces (15%) was nearly complete after 24 h. A rapid concentration of radioactivity can be seen in the stomach and in the salivary and lachrymal glands. Rats killed 1 and 4 h after treatment showed by far the highest labeling in the accessory genital gland. High levels of nonextractable radioactivity were present in esophageal tissue and melanin. The half lives for the disappearance of radioactivity from various tissues are in the order of about 1 h. Eye and esophagus sections both showed nonextractable labeling after in vitro incubation with 14C-myosmine. In conclusion, the toxicological significance of myosmine accumulation in esophagus and accessory genital gland requires further investigations. Hair analysis might be applicable for myosmine biomonitoring, because of possible enrichment in melanin containing tissues.
Peter J Weina - One of the best experts on this subject based on the ideXlab platform.
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the distribution pattern of intravenous 14c artesunate in rat tissues by quantitative Whole Body Autoradiography and tissue dissection techniques
Journal of Pharmaceutical and Biomedical Analysis, 2008Co-Authors: Qigui Li, Jing Zhang, Peter J WeinaAbstract:Abstract Quantitative Whole-Body Autoradiography (QWBA) and liquid scintillation counting (LSC) have been conducted to determine the metabolic profiles and tissue distribution of [ 14 C] labeled artesunate (AS) injection in rats. The QWBA technique showed more accurate results in the quantification of radioactivity in 40 organs and tissues, compared to 19 organs with the LSC technique. The benefit of QWBA was especially apparent on measurements of bile, bone marrow, and gland organs; however, the LSC method produced more relevant findings than QWBA. Particularly, the LSC method allowed access to the following distribution patterns that were unavailable via QWBA performance: such as pharmacokinetic evaluation of radiolabeled AS in blood and plasma, tissue/plasma partition coefficients, conversion pathway of AS to dihydroartemisinin (DHA, an active and major metabolite of AS), unchanged AS and DHA in plasma, mass balance assessment, urinary and faecal eliminations, drug pathway with conjugation, [ 14 C] AS binding with RBC and plasma protein, and metabolites identification. Even though the each method has its own advantages, common profiles were obtained from the two processes as shown in the results of the biliary metabolism, long-lasting metabolites, tissue distribution profiles, and multiple concentration peaks, which indicate a [ 14 C] AS enterohepatic circulation.
Claire Henson - One of the best experts on this subject based on the ideXlab platform.
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quantitative Whole Body Autoradiography past present and future
Bioanalysis, 2015Co-Authors: Andrew Mcewen, Claire HensonAbstract:Traditional bioanalytical measurements determine concentrations of drug and metabolites in plasma; however, most drugs exert their effects in defined target tissues. As there is no clear relation between concentrations in plasma and those in tissue, alternative methods must be employed to study the absorption, distribution, metabolism and excretion properties of new therapeutic agents. Quantitative Whole-Body Autoradiography is used in the drug development process to determine the distribution and concentrations of radiolabeled test compounds in laboratory animals. Quantitative Whole-Body Autoradiography can provide information on tissue PKs, penetration, accumulation and retention. Although the technique is considered the industry standard for performing preclinical tissue distribution studies, it is perhaps timely, 60 years after the first reported use of the method, to re-assess the technique against modern alternatives.
Lori Kraus - One of the best experts on this subject based on the ideXlab platform.
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quantitative Whole Body Autoradiography in the pharmaceutical industry survey results on study design methods and regulatory compliance
Journal of Pharmacological and Toxicological Methods, 2001Co-Authors: Eric Solon, Lori KrausAbstract:Introduction: Quantitative Whole-Body Autoradiography (QWBA) is a technique used to determine the tissue distribution of radiolabeled compounds in laboratory animals. This relatively new technique is quickly replacing wet-tissue dissection techniques, which, up to now, have been used by the pharmaceutical industry when performing tissue distribution studies to develop new drugs and to address regulatory compliance needs. In an effort to harmonize QWBA procedures across the pharmaceutical industry, the Society for Whole Body Autoradiography (SWBA) surveyed its membership to gain insight into the procedures and practices being used to perform tissue distribution studies conducted in support of drug development. Methods: The survey polled 29 respondents, who represent pharmaceutical companies in the United States, Europe, and Asia. Participants answered approximately 50 questions related to study design, applications, Autoradiography methods, tissue quantitation, and regulatory compliance. Results: The survey revealed general consistencies and inconsistencies among the labs that responded. Consistencies were related to: isotope use and doses of radioactivity, number of animals per time point, exsanguination of animals, freezing methods, section thickness, tissue collection lists, section lyophilization, imaging technology, blood and calibration standards, tissues and sections sampled for quantitation, use of QWBA data for human dosimetry, and QWBA method validation. Inconsistencies were related to: number of time points used, euthanasia methods, carcass freezing time, microtome calibration, section thickness verification, sample collection, validation of commercial standards, use of background measurements during calibration, definition of limits of quantitation, reporting of extrapolated values, reexposure of section to determine low levels, computer system validation, definitions of raw data, audit trail documentation, studies performed under Good Laboratory Practices (GLP) vs. non-GLP conditions. Discussion: The survey indicated that most labs are now using QWBA to perform their tissue distribution studies and that these data have been submitted and accepted by regulatory authorities around the world. Procedures and practices involved in the design of these studies appear to vary somewhat. An important inconsistency found related to the number of time points used to determine the pharmacokinetic (PK) parameters for tissues, which may effect the reliability of these parameters for use in predicting human exposure to radioactivity during human radiolabeled studies. Survey results regarding QWBA methods indicated that there is a lot of consistency across surveyed labs; however, there are some inconsistent areas that raise regulatory compliance issues and these are related to the verification of section thickness, validation of commercial standards and their use in quantitation, definitions of limits of quantitation, and consideration of background measurements during quantitation. This survey provides autoradiographers, managers, and regulators with an important reference on the state-of-the art of QWBA and shows that the technique has gained wide acceptance across the pharmaceutical industry. However, it also shows that there are some key areas, such as inconsistencies in the procedures used for quantitation, that investigators may want to probe further to assure that the highest quality and most useful studies are performed.
Brian Whitby - One of the best experts on this subject based on the ideXlab platform.
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the distribution pattern of radioactivity across different tissues in quantitative Whole Body Autoradiography qwba studies
European Journal of Pharmaceutical Sciences, 2006Co-Authors: Wolfgang F Richter, Volkmar Starke, Brian WhitbyAbstract:Abstract This study explored whether common rules exist for the distribution patterns across tissues in tissue distribution studies. To investigate this we tested whether tissue:plasma partition coefficients (PCs) of radioactivity are correlated with muscle:plasma PCs. The relationships between PCs of radioactivity in muscle and those in other tissues were investigated in 25 tissues for 20 structurally unrelated drug candidates. Tissue distribution data were obtained by quantitative Whole-Body Autoradiography. Linear regression analysis was performed for each tissue. Radioactivity from basic and acidic/neutral compounds was analyzed separately. Results for acidic/neutral compounds: for the majority of the tissues investigated, the tissue:plasma PCs were well correlated with muscle:plasma PCs (R2 > 0.7). Correlations were worse (R2
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The distribution pattern of radioactivity across different tissues in quantitative Whole-Body Autoradiography (QWBA) studies.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2006Co-Authors: Wolfgang F Richter, Volkmar Starke, Brian WhitbyAbstract:This study explored whether common rules exist for the distribution patterns across tissues in tissue distribution studies. To investigate this we tested whether tissue:plasma partition coefficients (PCs) of radioactivity are correlated with muscle:plasma PCs. The relationships between PCs of radioactivity in muscle and those in other tissues were investigated in 25 tissues for 20 structurally unrelated drug candidates. Tissue distribution data were obtained by quantitative Whole-Body Autoradiography. Linear regression analysis was performed for each tissue. Radioactivity from basic and acidic/neutral compounds was analyzed separately. Results for acidic/neutral compounds: for the majority of the tissues investigated, the tissue:plasma PCs were well correlated with muscle:plasma PCs (R2 > 0.7). Correlations were worse (R2 < 0.7) in blood, white fat, excretory organs and tissues protected by a penetration barrier (e.g. brain). Slope factors for the regression ranged from 0.2 (blood) to 3.8 (Harderian gland) and were correlated with neutral lipid contents in tissues. Results for basic compounds: in most tissues, slope factors appeared to be higher than for acidic/neutral compounds. Correlations, however, were poorer than for acidic/neutral compounds. Overall, the present study demonstrates that muscle:plasma PCs are indicative of the overall tissue distribution of drug-related material, as they are well correlated with tissue:plasma PCs in most other tissues. Correlations for acidic/neutral compounds differ from those for basic compounds. The found PC relationships provide an explanation for the distribution pattern across tissues usually seen in tissue distribution studies.
