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• W2133849435 endingPage "43" @default.
• W2133849435 startingPage "17" @default.
• W2133849435 abstract "Mass balance excretion studies in laboratory animals and humans using radiolabeled compounds represent a standard part of the development process for new drugs. From these studies, the total fate of drug-related material is obtained: mass balance, routes of excretion, and, with additional analyses, metabolic pathways. However, rarely does the mass balance in radiolabeled excretion studies truly achieve 100% recovery. Many definitions of cutoff criteria for mass balance that identify acceptable versus unacceptable recovery have been presented as ad hoc statements without a strong rationale. To address this, a retrospective analysis was undertaken to explore the overall performance of mass balance studies in both laboratory animal species and humans using data for 27 proprietary compounds within Pfizer and extensive review of published studies. The review has examined variation in recovery and the question of whether low recovery was a cause for concern in terms of drug safety. Overall, mean recovery was greater in rats and dogs than in humans. When the circulating half-life of total radioactivity is greater than 50 h, the recovery tends to be lower. Excretion data from the literature were queried as to whether drugs linked with toxicities associated with sequestration in tissues or covalent binding exhibit low mass balance. This was not the case, unless the sequestration led to a long elimination half-life of drug-related material. In the vast majority of cases, sequestration or concentration of drug-related material in an organ or tissue was without deleterious effect and, in some cases, was related to the pharmacological mechanism of action. Overall, from these data, recovery of radiolabel would normally be equal to or greater than 90%, 85%, and 80% in rat, dog, and human, respectively. Since several technical limitations can underlie a lack of mass balance and since mass balance data are not sensitive indicators of the potential for toxicity arising via tissue sequestration, absolute recovery in humans should not be used as a major decision criteria as to whether a radiolabeled study has met its objectives. Instead, the study should be seen as an integral part of drug development answering four principal questions: 1) Is the proposed clearance mechanism sufficiently supported by the identities of the drug-related materials in excreta, so as to provide a complete understanding of clearance and potential contributors to interpatient variability and drug-drug interactions? 2) What are the drug-related entities present in circulation that are the active principals contributing to primary and secondary pharmacology? 3) Are there findings (low extraction recovery of radiolabel from plasma, metabolite structures indicative of chemically reactive intermediates) that suggest potential safety issues requiring further risk assessment? 4) Do questions 2 and 3 have appropriate preclinical support in terms of pharmacology, safety pharmacology, and toxicology? Only if one or more of these four questions remain unanswered should additional mass balance studies be considered." @default.
• W2133849435 created "2016-06-24" @default.
• W2133849435 creator A5002542670 @default.
• W2133849435 creator A5027820159 @default.
• W2133849435 creator A5033271632 @default.
• W2133849435 creator A5085384943 @default.
• W2133849435 date "2007-01-01" @default.
• W2133849435 modified "2023-10-06" @default.
• W2133849435 title "What is the Objective of the Mass Balance Study? A Retrospective Analysis of Data in Animal and Human Excretion Studies Employing Radiolabeled Drugs" @default.
• W2133849435 cites W1485654772 @default.
• W2133849435 cites W1499225310 @default.
• W2133849435 cites W1518881239 @default.
• W2133849435 cites W152943885 @default.
• W2133849435 cites W1569963755 @default.
• W2133849435 cites W1788352485 @default.
• W2133849435 cites W1795186414 @default.
• W2133849435 cites W1855359827 @default.
• W2133849435 cites W1891945058 @default.
• W2133849435 cites W1910891420 @default.
• W2133849435 cites W1929872811 @default.
• W2133849435 cites W1964023467 @default.
• W2133849435 cites W1964822853 @default.
• W2133849435 cites W1965244035 @default.
• W2133849435 cites W1965965888 @default.
• W2133849435 cites W1967299205 @default.
• W2133849435 cites W1970722169 @default.
• W2133849435 cites W1971687708 @default.
• W2133849435 cites W1976044726 @default.
• W2133849435 cites W1976911376 @default.
• W2133849435 cites W1977685047 @default.
• W2133849435 cites W1977886913 @default.
• W2133849435 cites W1977996473 @default.
• W2133849435 cites W1978032928 @default.
• W2133849435 cites W1979827269 @default.
• W2133849435 cites W1981932605 @default.
• W2133849435 cites W1982888645 @default.
• W2133849435 cites W1983541140 @default.
• W2133849435 cites W1986269273 @default.
• W2133849435 cites W1988399857 @default.
• W2133849435 cites W1990168476 @default.
• W2133849435 cites W1990424351 @default.
• W2133849435 cites W1996091559 @default.
• W2133849435 cites W1996253623 @default.
• W2133849435 cites W1997277260 @default.
• W2133849435 cites W1998686052 @default.
• W2133849435 cites W1999058630 @default.
• W2133849435 cites W1999531425 @default.
• W2133849435 cites W2000796720 @default.
• W2133849435 cites W2003303784 @default.
• W2133849435 cites W2005079569 @default.
• W2133849435 cites W2006961439 @default.
• W2133849435 cites W2010705502 @default.
• W2133849435 cites W2010802924 @default.
• W2133849435 cites W2014213574 @default.
• W2133849435 cites W2014323502 @default.
• W2133849435 cites W2016029871 @default.
• W2133849435 cites W2017040916 @default.
• W2133849435 cites W2017542496 @default.
• W2133849435 cites W2019147271 @default.
• W2133849435 cites W2019259561 @default.
• W2133849435 cites W2020055953 @default.
• W2133849435 cites W2021845189 @default.
• W2133849435 cites W2022507089 @default.
• W2133849435 cites W2025111977 @default.
• W2133849435 cites W2025814760 @default.
• W2133849435 cites W2029136939 @default.
• W2133849435 cites W2029951339 @default.
• W2133849435 cites W2035787557 @default.
• W2133849435 cites W2035918126 @default.
• W2133849435 cites W2036168912 @default.
• W2133849435 cites W2038979944 @default.
• W2133849435 cites W2044245258 @default.
• W2133849435 cites W2044592304 @default.
• W2133849435 cites W2049912063 @default.
• W2133849435 cites W2051377562 @default.
• W2133849435 cites W2051654560 @default.
• W2133849435 cites W2052432365 @default.
• W2133849435 cites W2055761249 @default.
• W2133849435 cites W2057085148 @default.
• W2133849435 cites W2057804045 @default.
• W2133849435 cites W2060163930 @default.
• W2133849435 cites W2062439332 @default.
• W2133849435 cites W2062918215 @default.
• W2133849435 cites W2064954514 @default.
• W2133849435 cites W2065941911 @default.
• W2133849435 cites W2068140107 @default.
• W2133849435 cites W2071820805 @default.
• W2133849435 cites W2074492931 @default.
• W2133849435 cites W2074852633 @default.
• W2133849435 cites W2079617949 @default.
• W2133849435 cites W2080040682 @default.
• W2133849435 cites W2080279782 @default.
• W2133849435 cites W2082277309 @default.
• W2133849435 cites W2082371704 @default.
• W2133849435 cites W2083092785 @default.
• W2133849435 cites W2083894069 @default.
• W2133849435 cites W2083976911 @default.
• W2133849435 cites W2083980783 @default.

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