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Influence of menthol on caffeine disposition and pharmacodynamics in healthy female volunteers
The present study was undertaken to determine whether a single oral dose of menthol affects the metabolism of caffeine, a cytochrome P(450) 1A2 (CYP1A2) substrate, and pharmacological responses to caffeine in people. Eleven healthy female subjects participated in a randomized, double-blind, two-way...
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| Published in: | European journal of clinical pharmacology 2003-09, Vol.59 (5-6), p.417-422 |
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| container_end_page | 422 |
| container_issue | 5-6 |
| container_start_page | 417 |
| container_title | European journal of clinical pharmacology |
| container_volume | 59 |
| creator | GELAL, Ayse GUVEN, Hulya BALKAN, Dilara ARTOK, Levent BENOWITZ, Neal L |
| description | The present study was undertaken to determine whether a single oral dose of menthol affects the metabolism of caffeine, a cytochrome P(450) 1A2 (CYP1A2) substrate, and pharmacological responses to caffeine in people.
Eleven healthy female subjects participated in a randomized, double-blind, two-way crossover study, comparing the kinetics and effects of a single oral dose of caffeine (200 mg) in coffee taken together with a single oral dose of menthol (100 mg) or placebo capsules. Serum caffeine concentrations and cardiovascular and subjective parameters were measured throughout the study.
Co-administration of menthol resulted in an increase of caffeine t(max) values from 43.6+/-20.6 min (mean+/-SD) to 76.4+/-28.0 min ( P |
| doi_str_mv | 10.1007/s00228-003-0631-1 |
| format | article |
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Eleven healthy female subjects participated in a randomized, double-blind, two-way crossover study, comparing the kinetics and effects of a single oral dose of caffeine (200 mg) in coffee taken together with a single oral dose of menthol (100 mg) or placebo capsules. Serum caffeine concentrations and cardiovascular and subjective parameters were measured throughout the study.
Co-administration of menthol resulted in an increase of caffeine t(max) values from 43.6+/-20.6 min (mean+/-SD) to 76.4+/-28.0 min ( P<0.05). The C(max) values of caffeine were lower in the menthol phase than in the placebo phase, but this effect was not statistically significant ( P=0.06). (AUC)(0-24), (AUC)(0- infinity ), terminal half-life and oral clearance were not affected by menthol. Only nine subjects' cardiovascular data were included in the analysis because of technical problems during the measurements. After caffeine, heart rate decreased in both treatment phases. The maximum decrease in heart rate was less in the menthol phase (-8.9+/-3.9 beats/min) than in the placebo phase (-13.1+/-2.1 beats/min) ( P=0.024). There were no statistically significant differences in systolic and diastolic blood pressures between the two treatments.
We conclude that a single oral dose of pure menthol (100 mg) delays caffeine absorption and blunts the heart-rate slowing effect of caffeine, but does not affect caffeine metabolism. The possibility that menthol slows the absorption of other drugs should be considered.</description><identifier>ISSN: 0031-6970</identifier><identifier>EISSN: 1432-1041</identifier><identifier>DOI: 10.1007/s00228-003-0631-1</identifier><identifier>PMID: 12915954</identifier><language>eng</language><publisher>Heidelberg: Springer</publisher><subject>Administration, Oral ; Adolescent ; Adult ; Area Under Curve ; Biological and medical sciences ; Caffeine - blood ; Caffeine - pharmacokinetics ; Caffeine - pharmacology ; Coffee ; Cross-Over Studies ; Cytochrome P-450 CYP1A2 - metabolism ; Double-Blind Method ; Drug Interactions ; Female ; General pharmacology ; Half-Life ; Heart Rate - drug effects ; Humans ; Medical sciences ; Menthol - administration & dosage ; Menthol - pharmacology ; Middle Aged ; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions ; Pharmacology. Drug treatments ; Time Factors</subject><ispartof>European journal of clinical pharmacology, 2003-09, Vol.59 (5-6), p.417-422</ispartof><rights>2004 INIST-CNRS</rights><rights>Copyright Springer-Verlag 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c420t-b774b08e1fff0f8ada033f43ef57969e363530f7b3bdf45aa40e7af614e893fc3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15155845$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12915954$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GELAL, Ayse</creatorcontrib><creatorcontrib>GUVEN, Hulya</creatorcontrib><creatorcontrib>BALKAN, Dilara</creatorcontrib><creatorcontrib>ARTOK, Levent</creatorcontrib><creatorcontrib>BENOWITZ, Neal L</creatorcontrib><title>Influence of menthol on caffeine disposition and pharmacodynamics in healthy female volunteers</title><title>European journal of clinical pharmacology</title><addtitle>Eur J Clin Pharmacol</addtitle><description>The present study was undertaken to determine whether a single oral dose of menthol affects the metabolism of caffeine, a cytochrome P(450) 1A2 (CYP1A2) substrate, and pharmacological responses to caffeine in people.
Eleven healthy female subjects participated in a randomized, double-blind, two-way crossover study, comparing the kinetics and effects of a single oral dose of caffeine (200 mg) in coffee taken together with a single oral dose of menthol (100 mg) or placebo capsules. Serum caffeine concentrations and cardiovascular and subjective parameters were measured throughout the study.
Co-administration of menthol resulted in an increase of caffeine t(max) values from 43.6+/-20.6 min (mean+/-SD) to 76.4+/-28.0 min ( P<0.05). The C(max) values of caffeine were lower in the menthol phase than in the placebo phase, but this effect was not statistically significant ( P=0.06). (AUC)(0-24), (AUC)(0- infinity ), terminal half-life and oral clearance were not affected by menthol. Only nine subjects' cardiovascular data were included in the analysis because of technical problems during the measurements. After caffeine, heart rate decreased in both treatment phases. The maximum decrease in heart rate was less in the menthol phase (-8.9+/-3.9 beats/min) than in the placebo phase (-13.1+/-2.1 beats/min) ( P=0.024). There were no statistically significant differences in systolic and diastolic blood pressures between the two treatments.
We conclude that a single oral dose of pure menthol (100 mg) delays caffeine absorption and blunts the heart-rate slowing effect of caffeine, but does not affect caffeine metabolism. The possibility that menthol slows the absorption of other drugs should be considered.</description><subject>Administration, Oral</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Area Under Curve</subject><subject>Biological and medical sciences</subject><subject>Caffeine - blood</subject><subject>Caffeine - pharmacokinetics</subject><subject>Caffeine - pharmacology</subject><subject>Coffee</subject><subject>Cross-Over Studies</subject><subject>Cytochrome P-450 CYP1A2 - metabolism</subject><subject>Double-Blind Method</subject><subject>Drug Interactions</subject><subject>Female</subject><subject>General pharmacology</subject><subject>Half-Life</subject><subject>Heart Rate - drug effects</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Menthol - administration & dosage</subject><subject>Menthol - pharmacology</subject><subject>Middle Aged</subject><subject>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</subject><subject>Pharmacology. Drug treatments</subject><subject>Time Factors</subject><issn>0031-6970</issn><issn>1432-1041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNpFkMFq3DAQhkVoSTZpHiCXIgo9Op2xJMs-lpC2gUAv7bVClmdYB1vaSnZh374Ou5DTDDPfPwOfEHcI9whgvxSAum4rAFVBo7DCC7FDreoKQeM7sdsWWDWdhStxXcoLAJoO1KW4wrrbWqN34s9T5GmlGEgmljPFZZ8mmaIMnpnGSHIYyyGVcRm3oY-DPOx9nn1IwzH6eQxFjlHuyU_L_iiZZj-R_JemNS5EuXwQ79lPhW7P9Ub8_vb46-FH9fzz-9PD1-cq6BqWqrdW99ASMjNw6wcPSrFWxMZ2TUeqUUYB2171A2vjvQaynhvU1HaKg7oRn053Dzn9Xaks7iWtOW4vXY1a27Zu7AbhCQo5lZKJ3SGPs89Hh-BehbqTULd5c69CHW6Zj-fDaz_T8JY4G9yAz2fAl-Anzj6GsbxxBo1ptVH_AVO_fwc</recordid><startdate>20030901</startdate><enddate>20030901</enddate><creator>GELAL, Ayse</creator><creator>GUVEN, Hulya</creator><creator>BALKAN, Dilara</creator><creator>ARTOK, Levent</creator><creator>BENOWITZ, Neal L</creator><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20030901</creationdate><title>Influence of menthol on caffeine disposition and pharmacodynamics in healthy female volunteers</title><author>GELAL, Ayse ; GUVEN, Hulya ; BALKAN, Dilara ; ARTOK, Levent ; BENOWITZ, Neal L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c420t-b774b08e1fff0f8ada033f43ef57969e363530f7b3bdf45aa40e7af614e893fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Administration, Oral</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Area Under Curve</topic><topic>Biological and medical sciences</topic><topic>Caffeine - blood</topic><topic>Caffeine - pharmacokinetics</topic><topic>Caffeine - pharmacology</topic><topic>Coffee</topic><topic>Cross-Over Studies</topic><topic>Cytochrome P-450 CYP1A2 - metabolism</topic><topic>Double-Blind Method</topic><topic>Drug Interactions</topic><topic>Female</topic><topic>General pharmacology</topic><topic>Half-Life</topic><topic>Heart Rate - drug effects</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Menthol - administration & dosage</topic><topic>Menthol - pharmacology</topic><topic>Middle Aged</topic><topic>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</topic><topic>Pharmacology. Drug treatments</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GELAL, Ayse</creatorcontrib><creatorcontrib>GUVEN, Hulya</creatorcontrib><creatorcontrib>BALKAN, Dilara</creatorcontrib><creatorcontrib>ARTOK, Levent</creatorcontrib><creatorcontrib>BENOWITZ, Neal L</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>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>European journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GELAL, Ayse</au><au>GUVEN, Hulya</au><au>BALKAN, Dilara</au><au>ARTOK, Levent</au><au>BENOWITZ, Neal L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of menthol on caffeine disposition and pharmacodynamics in healthy female volunteers</atitle><jtitle>European journal of clinical pharmacology</jtitle><addtitle>Eur J Clin Pharmacol</addtitle><date>2003-09-01</date><risdate>2003</risdate><volume>59</volume><issue>5-6</issue><spage>417</spage><epage>422</epage><pages>417-422</pages><issn>0031-6970</issn><eissn>1432-1041</eissn><abstract>The present study was undertaken to determine whether a single oral dose of menthol affects the metabolism of caffeine, a cytochrome P(450) 1A2 (CYP1A2) substrate, and pharmacological responses to caffeine in people.
Eleven healthy female subjects participated in a randomized, double-blind, two-way crossover study, comparing the kinetics and effects of a single oral dose of caffeine (200 mg) in coffee taken together with a single oral dose of menthol (100 mg) or placebo capsules. Serum caffeine concentrations and cardiovascular and subjective parameters were measured throughout the study.
Co-administration of menthol resulted in an increase of caffeine t(max) values from 43.6+/-20.6 min (mean+/-SD) to 76.4+/-28.0 min ( P<0.05). The C(max) values of caffeine were lower in the menthol phase than in the placebo phase, but this effect was not statistically significant ( P=0.06). (AUC)(0-24), (AUC)(0- infinity ), terminal half-life and oral clearance were not affected by menthol. Only nine subjects' cardiovascular data were included in the analysis because of technical problems during the measurements. After caffeine, heart rate decreased in both treatment phases. The maximum decrease in heart rate was less in the menthol phase (-8.9+/-3.9 beats/min) than in the placebo phase (-13.1+/-2.1 beats/min) ( P=0.024). There were no statistically significant differences in systolic and diastolic blood pressures between the two treatments.
We conclude that a single oral dose of pure menthol (100 mg) delays caffeine absorption and blunts the heart-rate slowing effect of caffeine, but does not affect caffeine metabolism. The possibility that menthol slows the absorption of other drugs should be considered.</abstract><cop>Heidelberg</cop><cop>Berlin</cop><pub>Springer</pub><pmid>12915954</pmid><doi>10.1007/s00228-003-0631-1</doi><tpages>6</tpages></addata></record> |
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| ispartof | European journal of clinical pharmacology, 2003-09, Vol.59 (5-6), p.417-422 |
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| source | Springer Nature:Jisc Collections:Springer Nature Read and Publish 2023-2025: Springer Reading List |
| subjects | Administration, Oral Adolescent Adult Area Under Curve Biological and medical sciences Caffeine - blood Caffeine - pharmacokinetics Caffeine - pharmacology Coffee Cross-Over Studies Cytochrome P-450 CYP1A2 - metabolism Double-Blind Method Drug Interactions Female General pharmacology Half-Life Heart Rate - drug effects Humans Medical sciences Menthol - administration & dosage Menthol - pharmacology Middle Aged Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions Pharmacology. Drug treatments Time Factors |
| title | Influence of menthol on caffeine disposition and pharmacodynamics in healthy female volunteers |
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