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1990 Fiscal Year Final Research Report Summary

Metabolism of Lidcaine : Metabolic Pathway and P-450 Selectivity, Relation with Drug and Disease

Research Project

Project/Area Number 63480352
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 麻酔学
Research InstitutionOsaka City University

Principal Investigator

NISHI Shin-ichi  Oska City University Medical School, Research Associate, 医学部, 助手 (20189244)

Co-Investigator(Kenkyū-buntansha) ASADA Akira  Osaka City University Medical School, Assistant Professor, 医学部, 助教授 (00047367)
Project Period (FY) 1988 – 1990
KeywordsLidocaine / Human liver microsome / Cytochrome P-450 / P-450_<NF> / P-450_<PA> / P-450_<MP>
Research Abstract

The metabolism of lidocaine by human heptic microsome and purified human hepatic cytochrome P-450 (P-450) isozymes, P-450_<NF> , P-450_<PA> and P-450_<MP> was studied. Microsome was prepared from normal hepatic tissue around the hepatoma cells that was obtained during hepatic surgery.Content of P-450, NADPH cytochrome P-450 reductase and cytochrome b_5 was lower than those of rat hepatic microsome, and strong interindividual variance was detected. Human hepatic microsome produced N-dealkylated metabolite, monoethylglycinexylidide (MEGX) and ring hydroxylated one (3-OH LID). There was not any relationship between the content of P-450, formation rate of these metabolites and preoperatively administered drugs like diuretics, antihypertesive drugs. By Western blotting technique, P-450_<NF> was proved to be the major isozyme of human hepatic microsome and strong correlation was detected between the content of P-450_<NF> and formation rate of MEGX, rate of nifedipine oxidation and testosterone 16B-hydroxylation. This suggests that these reactions were catalyzed by selectively P-450_<NF>. In a reconstituted system with dilauroylphosehatidylcholine. MEGX was produced by each isozyme of P-450, but most effectively by P-450_<NF> and 3-OH LID was selectively by P-450_<PA>. Formation rate of MEGX was inhibited approximately by 40% by antibody raised against P-450X_<nf> in white rabbit. These results indicates that P-450_<nf> is the major isozyme of P-450 which is involved in the metabolism of lidocaine in human liver.

  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] 小田 裕: "局所麻酔薬リドカインのチトクロ-ムPー450による代謝" 麻酔薬代謝と肝腎障害. 9. 57-60 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 榎本 小弓: "ヒト肝ミクロゾ-ムによるリドカイン代謝" 麻酔薬代謝と肝腎障害. 10. 1-4 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oda,Yutaka: "Metabolism of lidocalne by purified rat liver microsomal cytochrome pー450 Isozymes" Biochemical Pharmacology. 38. 4439-4444 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 吉田 範子: "Pentobarhitcl 大寮法前後における Diphenylhydantoln の血中洸反の維移と Vmax,Km の変化について" 麻酔薬代謝と臓器障害. 11. 5-8 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小田 裕: "ヒト肝ミクロゾ-ムによるメピハカインの代謝について" 麻酔薬代謝と臓器障害. 11. 9-12 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imacka,Susamo: "Lidocaine metabolism by human cytochrome Pー450_s purified from hepatic microsmes: comparison of those with that heqatic cytochromes Pー450_S" Jcurnal of Pharmacology and Experimental Therajeatics. 255. 1385-1391 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] ODA, Y et al: "Metabolism of lidocaine by rat liver cytochrome P-450" Hiroshima J Anesth. 24suppl.57-60 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] ENOMOTO, K et al: "Metabolism of lidocaine by human liver microsomal cytochrome P-450" Hiroshima J Anesth. 25suppl.1-4 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] ODA, Y et al: "Metabolism of lidocaine by purified rat liver microsomal cytochrome p-450 isozymes" Biochem Pharmacol. 38. 4439-4444 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] ODA, Y et al: "Metabolism of mepivacaine by rat liver microsomes" Hiroshima J Anesth. 26suppl.9-12 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] IMAOKA, S et al: "Lidocaine metabolism by human liver cytochrome P-450s purified from hepatic microsomes : comparison of those with rat hepatic cytochrome P-450s" J Pharmacol Exp Ther. 255. 1385-1391 (1990)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-08-12  

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