Study of blood and brain lithium pharmacokinetics in the rat according to three different modalities of poisoning
Lithium-induced neurotoxicity may be life threatening. Three patterns have been described, including acute, acute-on-chronic, and chronic poisoning, with unexplained discrepancies in the relationship between clinical features and plasma lithium concentrations. Our objective was to investigate differ...
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| Veröffentlicht in: | Toxicological Sciences 2015-01, Vol.143 (1), p.185-195 |
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| creator | Hanak, Anne-Sophie Chevillard, Lucie El Balkhi, Souleiman Risède, Patricia Peoc'h, Katell Mégarbane, Bruno |
| description | Lithium-induced neurotoxicity may be life threatening. Three patterns have been described, including acute, acute-on-chronic, and chronic poisoning, with unexplained discrepancies in the relationship between clinical features and plasma lithium concentrations. Our objective was to investigate differences in plasma, erythrocyte, cerebrospinal fluid, and brain lithium pharmacokinetics using a multicompartmental approach in rat models mimicking the three human intoxication patterns. We developed acute (intraperitoneal administration of 185 mg/kg Li₂CO₃ in naive rats), acute-on-chronic (intraperitoneal administration of 185 mg/kg Li₂CO₃ in rats receiving 800 mg/l Li₂CO₃ in water during 28 days), and chronic poisoning models (intraperitoneal administration of 74 mg/kg Li₂CO₃ during 5 days in rats with 15 mg/kg K₂Cr₂O₇-induced renal failure). Delayed absorption (4.03 vs 0.31 h), increased plasma elimination (0.65 vs 0.37 l/kg/h) and shorter half-life (1.75 vs 2.68 h) were observed in acute-on-chronically compared with acutely poisoned rats. Erythrocyte and cerebrospinal fluid kinetics paralleled plasma kinetics in both models. Brain lithium distribution was rapid (as early as 15 min), inhomogeneous and with delayed elimination (over 78 h). However, brain lithium accumulation was more marked in acute-on-chronically than acutely poisoned rats [area-under-the-curve of brain concentrations (379 ± 41 vs 295 ± 26, P |
| doi_str_mv | 10.1093/toxsci/kfu224 |
| format | Article |
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Three patterns have been described, including acute, acute-on-chronic, and chronic poisoning, with unexplained discrepancies in the relationship between clinical features and plasma lithium concentrations. Our objective was to investigate differences in plasma, erythrocyte, cerebrospinal fluid, and brain lithium pharmacokinetics using a multicompartmental approach in rat models mimicking the three human intoxication patterns. We developed acute (intraperitoneal administration of 185 mg/kg Li₂CO₃ in naive rats), acute-on-chronic (intraperitoneal administration of 185 mg/kg Li₂CO₃ in rats receiving 800 mg/l Li₂CO₃ in water during 28 days), and chronic poisoning models (intraperitoneal administration of 74 mg/kg Li₂CO₃ during 5 days in rats with 15 mg/kg K₂Cr₂O₇-induced renal failure). Delayed absorption (4.03 vs 0.31 h), increased plasma elimination (0.65 vs 0.37 l/kg/h) and shorter half-life (1.75 vs 2.68 h) were observed in acute-on-chronically compared with acutely poisoned rats. Erythrocyte and cerebrospinal fluid kinetics paralleled plasma kinetics in both models. Brain lithium distribution was rapid (as early as 15 min), inhomogeneous and with delayed elimination (over 78 h). However, brain lithium accumulation was more marked in acute-on-chronically than acutely poisoned rats [area-under-the-curve of brain concentrations (379 ± 41 vs 295 ± 26, P < .05) and brain-to-plasma ratio (45 ± 10 vs 8 ± 2, P < .0001) at 54 h]. Moreover, brain lithium distribution was increased in chronically compared with acute-on-chronically poisoned rats (brain-to-plasma ratio: 9 ± 1 vs 3 ± 0, P < .01). In conclusion, prolonged rat exposure results in brain lithium accumulation, which is more marked in the presence of renal failure. Our data suggest that differences in plasma and brain kinetics may at least partially explain the observed variability between human intoxication patterns.</description><identifier>ISSN: 1096-6080</identifier><identifier>EISSN: 1096-0929</identifier><identifier>EISSN: 1096-6099</identifier><identifier>DOI: 10.1093/toxsci/kfu224</identifier><identifier>PMID: 25354763</identifier><language>eng</language><publisher>United States: Oxford University Press (OUP)</publisher><subject>Acute Disease ; Animals ; Area Under Curve ; Brain - metabolism ; Chronic Disease ; Disease Models, Animal ; Drug Administration Schedule ; Erythrocytes - metabolism ; Half-Life ; Injections, Intraperitoneal ; Life Sciences ; Lithium Carbonate - administration & dosage ; Lithium Carbonate - blood ; Lithium Carbonate - cerebrospinal fluid ; Lithium Carbonate - pharmacokinetics ; Lithium Carbonate - toxicity ; Male ; Metabolic Clearance Rate ; Models, Biological ; Neurotoxicity Syndromes - blood ; Neurotoxicity Syndromes - cerebrospinal fluid ; Neurotoxicity Syndromes - etiology ; Neurotoxicity Syndromes - metabolism ; Poisoning - blood ; Poisoning - cerebrospinal fluid ; Poisoning - metabolism ; Potassium Dichromate ; Rats, Sprague-Dawley ; Renal Insufficiency - chemically induced ; Renal Insufficiency - metabolism ; Toxicology</subject><ispartof>Toxicological Sciences, 2015-01, Vol.143 (1), p.185-195</ispartof><rights>The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c432t-b08b45ffc746043f215daf578484d842d4579eaa7cdb94a84adb1c9968bdde293</citedby><cites>FETCH-LOGICAL-c432t-b08b45ffc746043f215daf578484d842d4579eaa7cdb94a84adb1c9968bdde293</cites><orcidid>0000-0002-2522-2764 ; 0000-0003-2910-9117</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25354763$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03822968$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Hanak, Anne-Sophie</creatorcontrib><creatorcontrib>Chevillard, Lucie</creatorcontrib><creatorcontrib>El Balkhi, Souleiman</creatorcontrib><creatorcontrib>Risède, Patricia</creatorcontrib><creatorcontrib>Peoc'h, Katell</creatorcontrib><creatorcontrib>Mégarbane, Bruno</creatorcontrib><title>Study of blood and brain lithium pharmacokinetics in the rat according to three different modalities of poisoning</title><title>Toxicological Sciences</title><addtitle>Toxicol Sci</addtitle><description>Lithium-induced neurotoxicity may be life threatening. Three patterns have been described, including acute, acute-on-chronic, and chronic poisoning, with unexplained discrepancies in the relationship between clinical features and plasma lithium concentrations. Our objective was to investigate differences in plasma, erythrocyte, cerebrospinal fluid, and brain lithium pharmacokinetics using a multicompartmental approach in rat models mimicking the three human intoxication patterns. We developed acute (intraperitoneal administration of 185 mg/kg Li₂CO₃ in naive rats), acute-on-chronic (intraperitoneal administration of 185 mg/kg Li₂CO₃ in rats receiving 800 mg/l Li₂CO₃ in water during 28 days), and chronic poisoning models (intraperitoneal administration of 74 mg/kg Li₂CO₃ during 5 days in rats with 15 mg/kg K₂Cr₂O₇-induced renal failure). Delayed absorption (4.03 vs 0.31 h), increased plasma elimination (0.65 vs 0.37 l/kg/h) and shorter half-life (1.75 vs 2.68 h) were observed in acute-on-chronically compared with acutely poisoned rats. Erythrocyte and cerebrospinal fluid kinetics paralleled plasma kinetics in both models. Brain lithium distribution was rapid (as early as 15 min), inhomogeneous and with delayed elimination (over 78 h). However, brain lithium accumulation was more marked in acute-on-chronically than acutely poisoned rats [area-under-the-curve of brain concentrations (379 ± 41 vs 295 ± 26, P < .05) and brain-to-plasma ratio (45 ± 10 vs 8 ± 2, P < .0001) at 54 h]. Moreover, brain lithium distribution was increased in chronically compared with acute-on-chronically poisoned rats (brain-to-plasma ratio: 9 ± 1 vs 3 ± 0, P < .01). In conclusion, prolonged rat exposure results in brain lithium accumulation, which is more marked in the presence of renal failure. Our data suggest that differences in plasma and brain kinetics may at least partially explain the observed variability between human intoxication patterns.</description><subject>Acute Disease</subject><subject>Animals</subject><subject>Area Under Curve</subject><subject>Brain - metabolism</subject><subject>Chronic Disease</subject><subject>Disease Models, Animal</subject><subject>Drug Administration Schedule</subject><subject>Erythrocytes - metabolism</subject><subject>Half-Life</subject><subject>Injections, Intraperitoneal</subject><subject>Life Sciences</subject><subject>Lithium Carbonate - administration & dosage</subject><subject>Lithium Carbonate - blood</subject><subject>Lithium Carbonate - cerebrospinal fluid</subject><subject>Lithium Carbonate - pharmacokinetics</subject><subject>Lithium Carbonate - toxicity</subject><subject>Male</subject><subject>Metabolic Clearance Rate</subject><subject>Models, Biological</subject><subject>Neurotoxicity Syndromes - blood</subject><subject>Neurotoxicity Syndromes - cerebrospinal fluid</subject><subject>Neurotoxicity Syndromes - etiology</subject><subject>Neurotoxicity Syndromes - metabolism</subject><subject>Poisoning - blood</subject><subject>Poisoning - cerebrospinal fluid</subject><subject>Poisoning - metabolism</subject><subject>Potassium Dichromate</subject><subject>Rats, Sprague-Dawley</subject><subject>Renal Insufficiency - chemically induced</subject><subject>Renal Insufficiency - metabolism</subject><subject>Toxicology</subject><issn>1096-6080</issn><issn>1096-0929</issn><issn>1096-6099</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kDtPwzAURi0EoqUwsiKvDKGO7Tw8VhVQpEoMwBz5SUyTONgOov-eVCmd7tV3z_2GA8Btih5SxMgyut8g7XJnBozpGZiPYZ4ghtn5cc9RiWbgKoQvhNI0R-wSzHBGMlrkZA6-3-Kg9tAZKBrnFOSdgsJz28HGxtoOLexr7lsu3c52OloZ4HiLtYaeR8ildF7Z7hNGN4Zea6isMdrrLsLWKT6WWB0O9b2zwXUjeg0uDG-CvjnOBfh4enxfb5Lt6_PLerVNJCU4JgKVgmbGyILmiBKD00xxkxUlLakqKVY0K5jmvJBKMMpLypVIJWN5KZTSmJEFuJ96a95Uvbct9_vKcVttVtvqkCFSYjzyP-nIJhMrvQvBa3N6SFF10FxNmqtJ88jfTXw_iFarE_3vlfwBmb585Q</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Hanak, Anne-Sophie</creator><creator>Chevillard, Lucie</creator><creator>El Balkhi, Souleiman</creator><creator>Risède, Patricia</creator><creator>Peoc'h, Katell</creator><creator>Mégarbane, Bruno</creator><general>Oxford University Press (OUP)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-2522-2764</orcidid><orcidid>https://orcid.org/0000-0003-2910-9117</orcidid></search><sort><creationdate>20150101</creationdate><title>Study of blood and brain lithium pharmacokinetics in the rat according to three different modalities of poisoning</title><author>Hanak, Anne-Sophie ; Chevillard, Lucie ; El Balkhi, Souleiman ; Risède, Patricia ; Peoc'h, Katell ; Mégarbane, Bruno</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c432t-b08b45ffc746043f215daf578484d842d4579eaa7cdb94a84adb1c9968bdde293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Acute Disease</topic><topic>Animals</topic><topic>Area Under Curve</topic><topic>Brain - metabolism</topic><topic>Chronic Disease</topic><topic>Disease Models, Animal</topic><topic>Drug Administration Schedule</topic><topic>Erythrocytes - metabolism</topic><topic>Half-Life</topic><topic>Injections, Intraperitoneal</topic><topic>Life Sciences</topic><topic>Lithium Carbonate - administration & dosage</topic><topic>Lithium Carbonate - blood</topic><topic>Lithium Carbonate - cerebrospinal fluid</topic><topic>Lithium Carbonate - pharmacokinetics</topic><topic>Lithium Carbonate - toxicity</topic><topic>Male</topic><topic>Metabolic Clearance Rate</topic><topic>Models, Biological</topic><topic>Neurotoxicity Syndromes - blood</topic><topic>Neurotoxicity Syndromes - cerebrospinal fluid</topic><topic>Neurotoxicity Syndromes - etiology</topic><topic>Neurotoxicity Syndromes - metabolism</topic><topic>Poisoning - blood</topic><topic>Poisoning - cerebrospinal fluid</topic><topic>Poisoning - metabolism</topic><topic>Potassium Dichromate</topic><topic>Rats, Sprague-Dawley</topic><topic>Renal Insufficiency - chemically induced</topic><topic>Renal Insufficiency - metabolism</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hanak, Anne-Sophie</creatorcontrib><creatorcontrib>Chevillard, Lucie</creatorcontrib><creatorcontrib>El Balkhi, Souleiman</creatorcontrib><creatorcontrib>Risède, Patricia</creatorcontrib><creatorcontrib>Peoc'h, Katell</creatorcontrib><creatorcontrib>Mégarbane, Bruno</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Toxicological Sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hanak, Anne-Sophie</au><au>Chevillard, Lucie</au><au>El Balkhi, Souleiman</au><au>Risède, Patricia</au><au>Peoc'h, Katell</au><au>Mégarbane, Bruno</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Study of blood and brain lithium pharmacokinetics in the rat according to three different modalities of poisoning</atitle><jtitle>Toxicological Sciences</jtitle><addtitle>Toxicol Sci</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>143</volume><issue>1</issue><spage>185</spage><epage>195</epage><pages>185-195</pages><issn>1096-6080</issn><eissn>1096-0929</eissn><eissn>1096-6099</eissn><abstract>Lithium-induced neurotoxicity may be life threatening. Three patterns have been described, including acute, acute-on-chronic, and chronic poisoning, with unexplained discrepancies in the relationship between clinical features and plasma lithium concentrations. Our objective was to investigate differences in plasma, erythrocyte, cerebrospinal fluid, and brain lithium pharmacokinetics using a multicompartmental approach in rat models mimicking the three human intoxication patterns. We developed acute (intraperitoneal administration of 185 mg/kg Li₂CO₃ in naive rats), acute-on-chronic (intraperitoneal administration of 185 mg/kg Li₂CO₃ in rats receiving 800 mg/l Li₂CO₃ in water during 28 days), and chronic poisoning models (intraperitoneal administration of 74 mg/kg Li₂CO₃ during 5 days in rats with 15 mg/kg K₂Cr₂O₇-induced renal failure). Delayed absorption (4.03 vs 0.31 h), increased plasma elimination (0.65 vs 0.37 l/kg/h) and shorter half-life (1.75 vs 2.68 h) were observed in acute-on-chronically compared with acutely poisoned rats. Erythrocyte and cerebrospinal fluid kinetics paralleled plasma kinetics in both models. Brain lithium distribution was rapid (as early as 15 min), inhomogeneous and with delayed elimination (over 78 h). However, brain lithium accumulation was more marked in acute-on-chronically than acutely poisoned rats [area-under-the-curve of brain concentrations (379 ± 41 vs 295 ± 26, P < .05) and brain-to-plasma ratio (45 ± 10 vs 8 ± 2, P < .0001) at 54 h]. Moreover, brain lithium distribution was increased in chronically compared with acute-on-chronically poisoned rats (brain-to-plasma ratio: 9 ± 1 vs 3 ± 0, P < .01). In conclusion, prolonged rat exposure results in brain lithium accumulation, which is more marked in the presence of renal failure. Our data suggest that differences in plasma and brain kinetics may at least partially explain the observed variability between human intoxication patterns.</abstract><cop>United States</cop><pub>Oxford University Press (OUP)</pub><pmid>25354763</pmid><doi>10.1093/toxsci/kfu224</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-2522-2764</orcidid><orcidid>https://orcid.org/0000-0003-2910-9117</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elsevier ScienceDirect Journals; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Acute Disease Animals Area Under Curve Brain - metabolism Chronic Disease Disease Models, Animal Drug Administration Schedule Erythrocytes - metabolism Half-Life Injections, Intraperitoneal Life Sciences Lithium Carbonate - administration & dosage Lithium Carbonate - blood Lithium Carbonate - cerebrospinal fluid Lithium Carbonate - pharmacokinetics Lithium Carbonate - toxicity Male Metabolic Clearance Rate Models, Biological Neurotoxicity Syndromes - blood Neurotoxicity Syndromes - cerebrospinal fluid Neurotoxicity Syndromes - etiology Neurotoxicity Syndromes - metabolism Poisoning - blood Poisoning - cerebrospinal fluid Poisoning - metabolism Potassium Dichromate Rats, Sprague-Dawley Renal Insufficiency - chemically induced Renal Insufficiency - metabolism Toxicology |
| title | Study of blood and brain lithium pharmacokinetics in the rat according to three different modalities of poisoning |
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