Effects of Menthol on the Pharmacokinetics of Triazolam and Phenytoin
We have previously shown that menthol attenuates the anticoagulant effect of warfarin by increasing the expression levels of CYP3A and CYP2C in the liver. This study evaluated the effects of menthol on the pharmacokinetics of the CYP3A substrate triazolam and the CYP2C substrate phenytoin. Menthol w...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 2015/03/01, Vol.38(3), pp.454-460 |
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| creator | Hoshino, Motohiro Ikarashi, Nobutomo Hirobe, Ryuta Hayashi, Mami Hiraoka, Hironori Yokobori, Kohsuke Ochiai, Takumi Kusunoki, Yoshiki Kon, Risako Tajima, Masataka Ochiai, Wataru Sugiyama, Kiyoshi |
| description | We have previously shown that menthol attenuates the anticoagulant effect of warfarin by increasing the expression levels of CYP3A and CYP2C in the liver. This study evaluated the effects of menthol on the pharmacokinetics of the CYP3A substrate triazolam and the CYP2C substrate phenytoin. Menthol was orally administered to mice for 7 d. Twenty-four hours after the administration of menthol, triazolam was orally administered, and the plasma concentration was measured. In addition, the CYP3A metabolic activity for triazolam and the CYP3A expression level in the liver were determined. The effects of menthol on the pharmacokinetics of phenytoin were assessed in the same manner. In the menthol-treated group, the area under the blood concentration–time curve (AUC) of triazolam was lower and its clearance was higher compared with the control group. The CYP3A metabolic activity and CYP3A expression level in the liver were significantly increased in the menthol-treated group compared with the control group. Similarly, the AUC of phenytoin was lower and the hepatic CYP2C expression level was higher in the menthol-treated group. Thus, menthol lowered the plasma concentrations of triazolam and phenytoin when concurrently administered. These effects may be attributed to an increased metabolic activity for these drugs due to the increased expression of CYP3A and CYP2C in the liver. |
| doi_str_mv | 10.1248/bpb.b14-00764 |
| format | Article |
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This study evaluated the effects of menthol on the pharmacokinetics of the CYP3A substrate triazolam and the CYP2C substrate phenytoin. Menthol was orally administered to mice for 7 d. Twenty-four hours after the administration of menthol, triazolam was orally administered, and the plasma concentration was measured. In addition, the CYP3A metabolic activity for triazolam and the CYP3A expression level in the liver were determined. The effects of menthol on the pharmacokinetics of phenytoin were assessed in the same manner. In the menthol-treated group, the area under the blood concentration–time curve (AUC) of triazolam was lower and its clearance was higher compared with the control group. The CYP3A metabolic activity and CYP3A expression level in the liver were significantly increased in the menthol-treated group compared with the control group. Similarly, the AUC of phenytoin was lower and the hepatic CYP2C expression level was higher in the menthol-treated group. Thus, menthol lowered the plasma concentrations of triazolam and phenytoin when concurrently administered. These effects may be attributed to an increased metabolic activity for these drugs due to the increased expression of CYP3A and CYP2C in the liver.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.b14-00764</identifier><identifier>PMID: 25757928</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>Animals ; CYP ; Cytochrome P-450 CYP3A - metabolism ; Cytochrome P-450 Enzyme System - metabolism ; Drug Interactions ; Flavoring Agents - pharmacology ; Lamiaceae - chemistry ; Male ; menthol ; Menthol - pharmacology ; Mice, Inbred ICR ; phenytoin ; Phenytoin - blood ; Phenytoin - pharmacokinetics ; Plant Extracts - pharmacology ; triazolam ; Triazolam - blood ; Triazolam - pharmacokinetics ; warfarin</subject><ispartof>Biological and Pharmaceutical Bulletin, 2015/03/01, Vol.38(3), pp.454-460</ispartof><rights>2015 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c702t-e4bb603b6615b7610fc84c0737d074822f5ec5086863fe50349ae01e1264844e3</citedby><cites>FETCH-LOGICAL-c702t-e4bb603b6615b7610fc84c0737d074822f5ec5086863fe50349ae01e1264844e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25757928$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hoshino, Motohiro</creatorcontrib><creatorcontrib>Ikarashi, Nobutomo</creatorcontrib><creatorcontrib>Hirobe, Ryuta</creatorcontrib><creatorcontrib>Hayashi, Mami</creatorcontrib><creatorcontrib>Hiraoka, Hironori</creatorcontrib><creatorcontrib>Yokobori, Kohsuke</creatorcontrib><creatorcontrib>Ochiai, Takumi</creatorcontrib><creatorcontrib>Kusunoki, Yoshiki</creatorcontrib><creatorcontrib>Kon, Risako</creatorcontrib><creatorcontrib>Tajima, Masataka</creatorcontrib><creatorcontrib>Ochiai, Wataru</creatorcontrib><creatorcontrib>Sugiyama, Kiyoshi</creatorcontrib><creatorcontrib>Hoshi University</creatorcontrib><creatorcontrib>Department of Clinical Pharmacokinetics</creatorcontrib><title>Effects of Menthol on the Pharmacokinetics of Triazolam and Phenytoin</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>We have previously shown that menthol attenuates the anticoagulant effect of warfarin by increasing the expression levels of CYP3A and CYP2C in the liver. This study evaluated the effects of menthol on the pharmacokinetics of the CYP3A substrate triazolam and the CYP2C substrate phenytoin. Menthol was orally administered to mice for 7 d. Twenty-four hours after the administration of menthol, triazolam was orally administered, and the plasma concentration was measured. In addition, the CYP3A metabolic activity for triazolam and the CYP3A expression level in the liver were determined. The effects of menthol on the pharmacokinetics of phenytoin were assessed in the same manner. In the menthol-treated group, the area under the blood concentration–time curve (AUC) of triazolam was lower and its clearance was higher compared with the control group. The CYP3A metabolic activity and CYP3A expression level in the liver were significantly increased in the menthol-treated group compared with the control group. Similarly, the AUC of phenytoin was lower and the hepatic CYP2C expression level was higher in the menthol-treated group. Thus, menthol lowered the plasma concentrations of triazolam and phenytoin when concurrently administered. These effects may be attributed to an increased metabolic activity for these drugs due to the increased expression of CYP3A and CYP2C in the liver.</description><subject>Animals</subject><subject>CYP</subject><subject>Cytochrome P-450 CYP3A - metabolism</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Drug Interactions</subject><subject>Flavoring Agents - pharmacology</subject><subject>Lamiaceae - chemistry</subject><subject>Male</subject><subject>menthol</subject><subject>Menthol - pharmacology</subject><subject>Mice, Inbred ICR</subject><subject>phenytoin</subject><subject>Phenytoin - blood</subject><subject>Phenytoin - pharmacokinetics</subject><subject>Plant Extracts - pharmacology</subject><subject>triazolam</subject><subject>Triazolam - blood</subject><subject>Triazolam - pharmacokinetics</subject><subject>warfarin</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkb2PEzEQxS0E4sJBSYtWoqHZw992ShSFA-kQFEdt2c4s2eC1g70pjr-eSXIEicZjaX567-kNIa8ZvWFc2vdhH24Ckz2lRssnZMGENL3iTD0lC7pkttdM2SvyorUdRYZy8ZxccWWUWXK7IOv1MECcW1eG7gvkeVtSV3I3b6H7tvV18rH8HDPMYzwh93X0v0vyU-fzBgnID3MZ80vybPCpwavHeU2-f1zfrz71d19vP68-3PURjeceZAiaiqAxUzCa0SFaGakRZkONtJwPCqKiVlstBlBUyKUHyoBxLa2UIK7Ju7PuvpZfB2izm8YWISWfoRyaY1pzLaw2CtG3_6G7cqgZ0zmGa6WMVkeqP1OxltYqDG5fx8nXB8eoO_brsF-H_bpTv8i_eVQ9hAk2F_pvoQjcngHcjtGnkhPW9887NhPGkorjlCkUFZYKd_pKhSZSUy6ZRjNUWp2Vdm32P-Bi5SseI8EpmLBOHJ9LwMs24vEcZPEHOwih5A</recordid><startdate>20150301</startdate><enddate>20150301</enddate><creator>Hoshino, Motohiro</creator><creator>Ikarashi, Nobutomo</creator><creator>Hirobe, Ryuta</creator><creator>Hayashi, Mami</creator><creator>Hiraoka, Hironori</creator><creator>Yokobori, Kohsuke</creator><creator>Ochiai, Takumi</creator><creator>Kusunoki, Yoshiki</creator><creator>Kon, Risako</creator><creator>Tajima, Masataka</creator><creator>Ochiai, Wataru</creator><creator>Sugiyama, Kiyoshi</creator><general>The Pharmaceutical Society of Japan</general><general>Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20150301</creationdate><title>Effects of Menthol on the Pharmacokinetics of Triazolam and Phenytoin</title><author>Hoshino, Motohiro ; Ikarashi, Nobutomo ; Hirobe, Ryuta ; Hayashi, Mami ; Hiraoka, Hironori ; Yokobori, Kohsuke ; Ochiai, Takumi ; Kusunoki, Yoshiki ; Kon, Risako ; Tajima, Masataka ; Ochiai, Wataru ; Sugiyama, Kiyoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c702t-e4bb603b6615b7610fc84c0737d074822f5ec5086863fe50349ae01e1264844e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>CYP</topic><topic>Cytochrome P-450 CYP3A - metabolism</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Drug Interactions</topic><topic>Flavoring Agents - pharmacology</topic><topic>Lamiaceae - chemistry</topic><topic>Male</topic><topic>menthol</topic><topic>Menthol - pharmacology</topic><topic>Mice, Inbred ICR</topic><topic>phenytoin</topic><topic>Phenytoin - blood</topic><topic>Phenytoin - pharmacokinetics</topic><topic>Plant Extracts - pharmacology</topic><topic>triazolam</topic><topic>Triazolam - blood</topic><topic>Triazolam - pharmacokinetics</topic><topic>warfarin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hoshino, Motohiro</creatorcontrib><creatorcontrib>Ikarashi, Nobutomo</creatorcontrib><creatorcontrib>Hirobe, Ryuta</creatorcontrib><creatorcontrib>Hayashi, Mami</creatorcontrib><creatorcontrib>Hiraoka, Hironori</creatorcontrib><creatorcontrib>Yokobori, Kohsuke</creatorcontrib><creatorcontrib>Ochiai, Takumi</creatorcontrib><creatorcontrib>Kusunoki, Yoshiki</creatorcontrib><creatorcontrib>Kon, Risako</creatorcontrib><creatorcontrib>Tajima, Masataka</creatorcontrib><creatorcontrib>Ochiai, Wataru</creatorcontrib><creatorcontrib>Sugiyama, Kiyoshi</creatorcontrib><creatorcontrib>Hoshi University</creatorcontrib><creatorcontrib>Department of Clinical Pharmacokinetics</creatorcontrib><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>Hoshino, Motohiro</au><au>Ikarashi, Nobutomo</au><au>Hirobe, Ryuta</au><au>Hayashi, Mami</au><au>Hiraoka, Hironori</au><au>Yokobori, Kohsuke</au><au>Ochiai, Takumi</au><au>Kusunoki, Yoshiki</au><au>Kon, Risako</au><au>Tajima, Masataka</au><au>Ochiai, Wataru</au><au>Sugiyama, Kiyoshi</au><aucorp>Hoshi University</aucorp><aucorp>Department of Clinical Pharmacokinetics</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Menthol on the Pharmacokinetics of Triazolam and Phenytoin</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>2015-03-01</date><risdate>2015</risdate><volume>38</volume><issue>3</issue><spage>454</spage><epage>460</epage><pages>454-460</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>We have previously shown that menthol attenuates the anticoagulant effect of warfarin by increasing the expression levels of CYP3A and CYP2C in the liver. This study evaluated the effects of menthol on the pharmacokinetics of the CYP3A substrate triazolam and the CYP2C substrate phenytoin. Menthol was orally administered to mice for 7 d. Twenty-four hours after the administration of menthol, triazolam was orally administered, and the plasma concentration was measured. In addition, the CYP3A metabolic activity for triazolam and the CYP3A expression level in the liver were determined. The effects of menthol on the pharmacokinetics of phenytoin were assessed in the same manner. In the menthol-treated group, the area under the blood concentration–time curve (AUC) of triazolam was lower and its clearance was higher compared with the control group. The CYP3A metabolic activity and CYP3A expression level in the liver were significantly increased in the menthol-treated group compared with the control group. Similarly, the AUC of phenytoin was lower and the hepatic CYP2C expression level was higher in the menthol-treated group. Thus, menthol lowered the plasma concentrations of triazolam and phenytoin when concurrently administered. These effects may be attributed to an increased metabolic activity for these drugs due to the increased expression of CYP3A and CYP2C in the liver.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>25757928</pmid><doi>10.1248/bpb.b14-00764</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals CYP Cytochrome P-450 CYP3A - metabolism Cytochrome P-450 Enzyme System - metabolism Drug Interactions Flavoring Agents - pharmacology Lamiaceae - chemistry Male menthol Menthol - pharmacology Mice, Inbred ICR phenytoin Phenytoin - blood Phenytoin - pharmacokinetics Plant Extracts - pharmacology triazolam Triazolam - blood Triazolam - pharmacokinetics warfarin |
| title | Effects of Menthol on the Pharmacokinetics of Triazolam and Phenytoin |
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