INHIBITORY EFFECT OF DILTIAZEM ON DIAZEPAM METABOLISM IN THE MOUSE HEPATIC MICROSOMES
In order to elucidate the drug interaction between diltiazem and diazepam, the effect of diltiazem on the N-demethylation of diazepam in the mouse hepatic microsomes was investigated. Kinetic study showed that diltiazem noncompetitively inhibited the N-demethylation of diazepam with inhibition const...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 1993/03/15, Vol.16(3), pp.331-333 |
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| container_title | Biological & pharmaceutical bulletin |
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| creator | IHARA, Norihiko KOKUFU, Takatoshi SUGIOKA, Nobuyuki OHTA, Toshio NOSAKA, Kazuto |
| description | In order to elucidate the drug interaction between diltiazem and diazepam, the effect of diltiazem on the N-demethylation of diazepam in the mouse hepatic microsomes was investigated. Kinetic study showed that diltiazem noncompetitively inhibited the N-demethylation of diazepam with inhibition constant(Ki) value of 247.8 μM, indicating that diltiazem exhibits an inhibitory effect on the hepatic oxidative metabolism of diazepam. It was therefore suggested that diltiazem may impair the metabolism of diazepam in vivo. |
| doi_str_mv | 10.1248/bpb.16.331 |
| format | Article |
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Kinetic study showed that diltiazem noncompetitively inhibited the N-demethylation of diazepam with inhibition constant(Ki) value of 247.8 μM, indicating that diltiazem exhibits an inhibitory effect on the hepatic oxidative metabolism of diazepam. It was therefore suggested that diltiazem may impair the metabolism of diazepam in vivo.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.16.331</identifier><identifier>PMID: 8364486</identifier><language>eng</language><publisher>Tokyo: The Pharmaceutical Society of Japan</publisher><subject>Animals ; Antianginal agents. Coronary vasodilator agents ; Biological and medical sciences ; Cardiovascular system ; cytochrome P-450 ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System ; diazepam ; Diazepam - metabolism ; Diazepam - pharmacokinetics ; diltiazem ; Diltiazem - pharmacology ; drug interaction ; enzyme inhibition ; In Vitro Techniques ; Male ; Medical sciences ; Mice ; Mice, Inbred Strains ; Microsomes, Liver - drug effects ; Microsomes, Liver - metabolism ; Nordazepam - metabolism ; Oxidoreductases, N-Demethylating - antagonists & inhibitors ; Pharmacology. 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Kinetic study showed that diltiazem noncompetitively inhibited the N-demethylation of diazepam with inhibition constant(Ki) value of 247.8 μM, indicating that diltiazem exhibits an inhibitory effect on the hepatic oxidative metabolism of diazepam. It was therefore suggested that diltiazem may impair the metabolism of diazepam in vivo.</description><subject>Animals</subject><subject>Antianginal agents. Coronary vasodilator agents</subject><subject>Biological and medical sciences</subject><subject>Cardiovascular system</subject><subject>cytochrome P-450</subject><subject>Cytochrome P-450 Enzyme Inhibitors</subject><subject>Cytochrome P-450 Enzyme System</subject><subject>diazepam</subject><subject>Diazepam - metabolism</subject><subject>Diazepam - pharmacokinetics</subject><subject>diltiazem</subject><subject>Diltiazem - pharmacology</subject><subject>drug interaction</subject><subject>enzyme inhibition</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred Strains</subject><subject>Microsomes, Liver - drug effects</subject><subject>Microsomes, Liver - metabolism</subject><subject>Nordazepam - metabolism</subject><subject>Oxidoreductases, N-Demethylating - antagonists & inhibitors</subject><subject>Pharmacology. 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Coronary vasodilator agents</topic><topic>Biological and medical sciences</topic><topic>Cardiovascular system</topic><topic>cytochrome P-450</topic><topic>Cytochrome P-450 Enzyme Inhibitors</topic><topic>Cytochrome P-450 Enzyme System</topic><topic>diazepam</topic><topic>Diazepam - metabolism</topic><topic>Diazepam - pharmacokinetics</topic><topic>diltiazem</topic><topic>Diltiazem - pharmacology</topic><topic>drug interaction</topic><topic>enzyme inhibition</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred Strains</topic><topic>Microsomes, Liver - drug effects</topic><topic>Microsomes, Liver - metabolism</topic><topic>Nordazepam - metabolism</topic><topic>Oxidoreductases, N-Demethylating - antagonists & inhibitors</topic><topic>Pharmacology. Drug treatments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>IHARA, Norihiko</creatorcontrib><creatorcontrib>KOKUFU, Takatoshi</creatorcontrib><creatorcontrib>SUGIOKA, Nobuyuki</creatorcontrib><creatorcontrib>OHTA, Toshio</creatorcontrib><creatorcontrib>NOSAKA, Kazuto</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biological & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>IHARA, Norihiko</au><au>KOKUFU, Takatoshi</au><au>SUGIOKA, Nobuyuki</au><au>OHTA, Toshio</au><au>NOSAKA, Kazuto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>INHIBITORY EFFECT OF DILTIAZEM ON DIAZEPAM METABOLISM IN THE MOUSE HEPATIC MICROSOMES</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>1993</date><risdate>1993</risdate><volume>16</volume><issue>3</issue><spage>331</spage><epage>333</epage><pages>331-333</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>In order to elucidate the drug interaction between diltiazem and diazepam, the effect of diltiazem on the N-demethylation of diazepam in the mouse hepatic microsomes was investigated. Kinetic study showed that diltiazem noncompetitively inhibited the N-demethylation of diazepam with inhibition constant(Ki) value of 247.8 μM, indicating that diltiazem exhibits an inhibitory effect on the hepatic oxidative metabolism of diazepam. It was therefore suggested that diltiazem may impair the metabolism of diazepam in vivo.</abstract><cop>Tokyo</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>8364486</pmid><doi>10.1248/bpb.16.331</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record> |
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| source | J-STAGE Free; MEDLINE; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Animals Antianginal agents. Coronary vasodilator agents Biological and medical sciences Cardiovascular system cytochrome P-450 Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 Enzyme System diazepam Diazepam - metabolism Diazepam - pharmacokinetics diltiazem Diltiazem - pharmacology drug interaction enzyme inhibition In Vitro Techniques Male Medical sciences Mice Mice, Inbred Strains Microsomes, Liver - drug effects Microsomes, Liver - metabolism Nordazepam - metabolism Oxidoreductases, N-Demethylating - antagonists & inhibitors Pharmacology. Drug treatments |
| title | INHIBITORY EFFECT OF DILTIAZEM ON DIAZEPAM METABOLISM IN THE MOUSE HEPATIC MICROSOMES |
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