Pharmacokinetics of a New Orodispersible Tablet Formulation of Vardenafil: Results of Three Clinical Trials
Background: Vardenafil is a potent and highly selective oral phosphodiesterase type 5 (PDE-5) inhibitor that has been shown in numerous clinical trials and post-marketing surveillance studies to be safe and effective for improving erectile function in men with erectile dysfunction (ED). Until recent...
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| Veröffentlicht in: | Clinical drug investigation 2011, Vol.31 (1), p.27-41 |
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| creator | Heinig, Roland Weimann, Boris Dietrich, Hartmut Böttcher, Michael-Friedrich |
| description | Background:
Vardenafil is a potent and highly selective oral phosphodiesterase type 5 (PDE-5) inhibitor that has been shown in numerous clinical trials and post-marketing surveillance studies to be safe and effective for improving erectile function in men with erectile dysfunction (ED). Until recently, the drug was only available as a film-coated tablet (FCT). A new orodispersible tablet (ODT) formulation of vardenafil has been developed that disintegrates in the subject’s mouth without the need for water or other liquids.
Objective:
To characterize the pharmacokinetics of a new 10 mg ODT formulation of vardenafil.
Methods:
Three clinical trials were conducted: (i) a randomized 4-fold crossover study to assess the effect of food and water on the pharmacokinetics of vardenafil ODT, compared with vardenafil FCT, in healthy men; (ii) a phase I study to assess single and multiple doses of vardenafil ODT, compared with a single dose of vardenafil FCT, in young and elderly men with ED; and (iii) a pharmacokinetic substudy of a phase III trial in men of broad age range with ED.
Results:
Vardenafil ODT was rapidly absorbed after oral administration without water, with a similar pharmacokinetic profile to vardenafil FCT, except that the ODT exhibited significantly greater bioavailability. After a single dose, the geometric mean area under the plasma concentration-time curve from time zero to infinity (AUC
∞
) of vardenafil ODT increased by 21–44% compared with the FCT. There was no consistent difference in geometric mean maximum vardenafil plasma concentration (C
max
) between the two formulations. Geometric mean AUC∞ and C
max
were increased by 41% and 24%, respectively, in men with ED aged ≥65 years compared with those aged |
| doi_str_mv | 10.2165/11584950-000000000-00000 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_cross</sourceid><recordid>TN_cdi_gale_infotracmisc_A241947523</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A241947523</galeid><sourcerecordid>A241947523</sourcerecordid><originalsourceid>FETCH-LOGICAL-c376t-e0bd55188dcec75aae05778d9eb7599a61a169670cfbebfc29d9eb2754618a173</originalsourceid><addsrcrecordid>eNqFkFFLwzAUhYMobk7_ghR87kyyJmkex3A6GM6H6WtI09uZ2TYj6RD_vZl1giCYC8mBe75L7kEoIXhMCWe3hLA8kwyn-Hh6dYKGhAiZEkny0y89SSnjkwG6CGGLMeGE03M0oFhSlmV0iBZPr9o32rg320JnTUhclejkEd6TlXelDTvwwRY1JGsd7y6ZO9_sa91Z1x6sL9qX0OrK1pforNJ1gKvvd4Se53fr2UO6XN0vZtNlaiaCdyngomSM5HlpwAimNWAmRF5KKASTUnOiCZdcYFMVUFSGykOLCpZxkuu40Ajd9HM3ugZl28p1XpvGBqOmNCMyE4xOomv8hytWCY01roX4Y_gN5D1gvAvBQ6V23jbafyiC1SF0dQxd_YTeq4he9-huXzRQ_oDHlKNB9oYQW-0GvNq6vW9jSv8P_wTkMowG</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Pharmacokinetics of a New Orodispersible Tablet Formulation of Vardenafil: Results of Three Clinical Trials</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Heinig, Roland ; Weimann, Boris ; Dietrich, Hartmut ; Böttcher, Michael-Friedrich</creator><creatorcontrib>Heinig, Roland ; Weimann, Boris ; Dietrich, Hartmut ; Böttcher, Michael-Friedrich</creatorcontrib><description>Background:
Vardenafil is a potent and highly selective oral phosphodiesterase type 5 (PDE-5) inhibitor that has been shown in numerous clinical trials and post-marketing surveillance studies to be safe and effective for improving erectile function in men with erectile dysfunction (ED). Until recently, the drug was only available as a film-coated tablet (FCT). A new orodispersible tablet (ODT) formulation of vardenafil has been developed that disintegrates in the subject’s mouth without the need for water or other liquids.
Objective:
To characterize the pharmacokinetics of a new 10 mg ODT formulation of vardenafil.
Methods:
Three clinical trials were conducted: (i) a randomized 4-fold crossover study to assess the effect of food and water on the pharmacokinetics of vardenafil ODT, compared with vardenafil FCT, in healthy men; (ii) a phase I study to assess single and multiple doses of vardenafil ODT, compared with a single dose of vardenafil FCT, in young and elderly men with ED; and (iii) a pharmacokinetic substudy of a phase III trial in men of broad age range with ED.
Results:
Vardenafil ODT was rapidly absorbed after oral administration without water, with a similar pharmacokinetic profile to vardenafil FCT, except that the ODT exhibited significantly greater bioavailability. After a single dose, the geometric mean area under the plasma concentration-time curve from time zero to infinity (AUC
∞
) of vardenafil ODT increased by 21–44% compared with the FCT. There was no consistent difference in geometric mean maximum vardenafil plasma concentration (C
max
) between the two formulations. Geometric mean AUC∞ and C
max
were increased by 41% and 24%, respectively, in men with ED aged ≥65 years compared with those aged <65 years. Multiple dosing or administration of vardenafil ODT with food had no meaningful effect on the pharmacokinetics of vardenafil. Vardenafil ODT was well tolerated.
Conclusion:
Vardenafil ODT should be taken without water. Partial absorption of vardenafil through the oral mucosa results in an unexpected extent of suprabioavailability of the ODT formulation. Vardenafil ODT is a convenient formulation, with pharmacokinetic and safety characteristics that are appropriate for the treatment of ED.</description><identifier>ISSN: 1173-2563</identifier><identifier>EISSN: 1179-1918</identifier><identifier>DOI: 10.2165/11584950-000000000-00000</identifier><identifier>PMID: 20925442</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject><![CDATA[Administration, Oral ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Drug therapy ; Humans ; Imidazoles - administration & dosage ; Imidazoles - adverse effects ; Imidazoles - pharmacokinetics ; Impotence ; Internal Medicine ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Original Research Article ; Pharmacokinetics ; Pharmacology/Toxicology ; Pharmacotherapy ; Phosphodiesterase 5 Inhibitors - administration & dosage ; Phosphodiesterase 5 Inhibitors - adverse effects ; Phosphodiesterase 5 Inhibitors - pharmacokinetics ; Piperazines - administration & dosage ; Piperazines - adverse effects ; Piperazines - pharmacokinetics ; Sulfones - administration & dosage ; Sulfones - adverse effects ; Sulfones - pharmacokinetics ; Tablets - administration & dosage ; Triazines - administration & dosage ; Triazines - adverse effects ; Triazines - pharmacokinetics ; Vardenafil Dihydrochloride]]></subject><ispartof>Clinical drug investigation, 2011, Vol.31 (1), p.27-41</ispartof><rights>Adis Data Information BV 2011</rights><rights>COPYRIGHT 2011 Wolters Kluwer Health, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c376t-e0bd55188dcec75aae05778d9eb7599a61a169670cfbebfc29d9eb2754618a173</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.2165/11584950-000000000-00000$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.2165/11584950-000000000-00000$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,4024,27923,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20925442$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Heinig, Roland</creatorcontrib><creatorcontrib>Weimann, Boris</creatorcontrib><creatorcontrib>Dietrich, Hartmut</creatorcontrib><creatorcontrib>Böttcher, Michael-Friedrich</creatorcontrib><title>Pharmacokinetics of a New Orodispersible Tablet Formulation of Vardenafil: Results of Three Clinical Trials</title><title>Clinical drug investigation</title><addtitle>Clin. Drug Investig</addtitle><addtitle>Clin Drug Investig</addtitle><description>Background:
Vardenafil is a potent and highly selective oral phosphodiesterase type 5 (PDE-5) inhibitor that has been shown in numerous clinical trials and post-marketing surveillance studies to be safe and effective for improving erectile function in men with erectile dysfunction (ED). Until recently, the drug was only available as a film-coated tablet (FCT). A new orodispersible tablet (ODT) formulation of vardenafil has been developed that disintegrates in the subject’s mouth without the need for water or other liquids.
Objective:
To characterize the pharmacokinetics of a new 10 mg ODT formulation of vardenafil.
Methods:
Three clinical trials were conducted: (i) a randomized 4-fold crossover study to assess the effect of food and water on the pharmacokinetics of vardenafil ODT, compared with vardenafil FCT, in healthy men; (ii) a phase I study to assess single and multiple doses of vardenafil ODT, compared with a single dose of vardenafil FCT, in young and elderly men with ED; and (iii) a pharmacokinetic substudy of a phase III trial in men of broad age range with ED.
Results:
Vardenafil ODT was rapidly absorbed after oral administration without water, with a similar pharmacokinetic profile to vardenafil FCT, except that the ODT exhibited significantly greater bioavailability. After a single dose, the geometric mean area under the plasma concentration-time curve from time zero to infinity (AUC
∞
) of vardenafil ODT increased by 21–44% compared with the FCT. There was no consistent difference in geometric mean maximum vardenafil plasma concentration (C
max
) between the two formulations. Geometric mean AUC∞ and C
max
were increased by 41% and 24%, respectively, in men with ED aged ≥65 years compared with those aged <65 years. Multiple dosing or administration of vardenafil ODT with food had no meaningful effect on the pharmacokinetics of vardenafil. Vardenafil ODT was well tolerated.
Conclusion:
Vardenafil ODT should be taken without water. Partial absorption of vardenafil through the oral mucosa results in an unexpected extent of suprabioavailability of the ODT formulation. Vardenafil ODT is a convenient formulation, with pharmacokinetic and safety characteristics that are appropriate for the treatment of ED.</description><subject>Administration, Oral</subject><subject>Adult</subject><subject>Age Factors</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Drug therapy</subject><subject>Humans</subject><subject>Imidazoles - administration & dosage</subject><subject>Imidazoles - adverse effects</subject><subject>Imidazoles - pharmacokinetics</subject><subject>Impotence</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Original Research Article</subject><subject>Pharmacokinetics</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacotherapy</subject><subject>Phosphodiesterase 5 Inhibitors - administration & dosage</subject><subject>Phosphodiesterase 5 Inhibitors - adverse effects</subject><subject>Phosphodiesterase 5 Inhibitors - pharmacokinetics</subject><subject>Piperazines - administration & dosage</subject><subject>Piperazines - adverse effects</subject><subject>Piperazines - pharmacokinetics</subject><subject>Sulfones - administration & dosage</subject><subject>Sulfones - adverse effects</subject><subject>Sulfones - pharmacokinetics</subject><subject>Tablets - administration & dosage</subject><subject>Triazines - administration & dosage</subject><subject>Triazines - adverse effects</subject><subject>Triazines - pharmacokinetics</subject><subject>Vardenafil Dihydrochloride</subject><issn>1173-2563</issn><issn>1179-1918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkFFLwzAUhYMobk7_ghR87kyyJmkex3A6GM6H6WtI09uZ2TYj6RD_vZl1giCYC8mBe75L7kEoIXhMCWe3hLA8kwyn-Hh6dYKGhAiZEkny0y89SSnjkwG6CGGLMeGE03M0oFhSlmV0iBZPr9o32rg320JnTUhclejkEd6TlXelDTvwwRY1JGsd7y6ZO9_sa91Z1x6sL9qX0OrK1pforNJ1gKvvd4Se53fr2UO6XN0vZtNlaiaCdyngomSM5HlpwAimNWAmRF5KKASTUnOiCZdcYFMVUFSGykOLCpZxkuu40Ajd9HM3ugZl28p1XpvGBqOmNCMyE4xOomv8hytWCY01roX4Y_gN5D1gvAvBQ6V23jbafyiC1SF0dQxd_YTeq4he9-huXzRQ_oDHlKNB9oYQW-0GvNq6vW9jSv8P_wTkMowG</recordid><startdate>2011</startdate><enddate>2011</enddate><creator>Heinig, Roland</creator><creator>Weimann, Boris</creator><creator>Dietrich, Hartmut</creator><creator>Böttcher, Michael-Friedrich</creator><general>Springer International Publishing</general><general>Wolters Kluwer Health, Inc</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></search><sort><creationdate>2011</creationdate><title>Pharmacokinetics of a New Orodispersible Tablet Formulation of Vardenafil</title><author>Heinig, Roland ; Weimann, Boris ; Dietrich, Hartmut ; Böttcher, Michael-Friedrich</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c376t-e0bd55188dcec75aae05778d9eb7599a61a169670cfbebfc29d9eb2754618a173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Administration, Oral</topic><topic>Adult</topic><topic>Age Factors</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Drug therapy</topic><topic>Humans</topic><topic>Imidazoles - administration & dosage</topic><topic>Imidazoles - adverse effects</topic><topic>Imidazoles - pharmacokinetics</topic><topic>Impotence</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Original Research Article</topic><topic>Pharmacokinetics</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacotherapy</topic><topic>Phosphodiesterase 5 Inhibitors - administration & dosage</topic><topic>Phosphodiesterase 5 Inhibitors - adverse effects</topic><topic>Phosphodiesterase 5 Inhibitors - pharmacokinetics</topic><topic>Piperazines - administration & dosage</topic><topic>Piperazines - adverse effects</topic><topic>Piperazines - pharmacokinetics</topic><topic>Sulfones - administration & dosage</topic><topic>Sulfones - adverse effects</topic><topic>Sulfones - pharmacokinetics</topic><topic>Tablets - administration & dosage</topic><topic>Triazines - administration & dosage</topic><topic>Triazines - adverse effects</topic><topic>Triazines - pharmacokinetics</topic><topic>Vardenafil Dihydrochloride</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Heinig, Roland</creatorcontrib><creatorcontrib>Weimann, Boris</creatorcontrib><creatorcontrib>Dietrich, Hartmut</creatorcontrib><creatorcontrib>Böttcher, Michael-Friedrich</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Clinical drug investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Heinig, Roland</au><au>Weimann, Boris</au><au>Dietrich, Hartmut</au><au>Böttcher, Michael-Friedrich</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetics of a New Orodispersible Tablet Formulation of Vardenafil: Results of Three Clinical Trials</atitle><jtitle>Clinical drug investigation</jtitle><stitle>Clin. Drug Investig</stitle><addtitle>Clin Drug Investig</addtitle><date>2011</date><risdate>2011</risdate><volume>31</volume><issue>1</issue><spage>27</spage><epage>41</epage><pages>27-41</pages><issn>1173-2563</issn><eissn>1179-1918</eissn><abstract>Background:
Vardenafil is a potent and highly selective oral phosphodiesterase type 5 (PDE-5) inhibitor that has been shown in numerous clinical trials and post-marketing surveillance studies to be safe and effective for improving erectile function in men with erectile dysfunction (ED). Until recently, the drug was only available as a film-coated tablet (FCT). A new orodispersible tablet (ODT) formulation of vardenafil has been developed that disintegrates in the subject’s mouth without the need for water or other liquids.
Objective:
To characterize the pharmacokinetics of a new 10 mg ODT formulation of vardenafil.
Methods:
Three clinical trials were conducted: (i) a randomized 4-fold crossover study to assess the effect of food and water on the pharmacokinetics of vardenafil ODT, compared with vardenafil FCT, in healthy men; (ii) a phase I study to assess single and multiple doses of vardenafil ODT, compared with a single dose of vardenafil FCT, in young and elderly men with ED; and (iii) a pharmacokinetic substudy of a phase III trial in men of broad age range with ED.
Results:
Vardenafil ODT was rapidly absorbed after oral administration without water, with a similar pharmacokinetic profile to vardenafil FCT, except that the ODT exhibited significantly greater bioavailability. After a single dose, the geometric mean area under the plasma concentration-time curve from time zero to infinity (AUC
∞
) of vardenafil ODT increased by 21–44% compared with the FCT. There was no consistent difference in geometric mean maximum vardenafil plasma concentration (C
max
) between the two formulations. Geometric mean AUC∞ and C
max
were increased by 41% and 24%, respectively, in men with ED aged ≥65 years compared with those aged <65 years. Multiple dosing or administration of vardenafil ODT with food had no meaningful effect on the pharmacokinetics of vardenafil. Vardenafil ODT was well tolerated.
Conclusion:
Vardenafil ODT should be taken without water. Partial absorption of vardenafil through the oral mucosa results in an unexpected extent of suprabioavailability of the ODT formulation. Vardenafil ODT is a convenient formulation, with pharmacokinetic and safety characteristics that are appropriate for the treatment of ED.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>20925442</pmid><doi>10.2165/11584950-000000000-00000</doi><tpages>15</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1173-2563 |
| ispartof | Clinical drug investigation, 2011, Vol.31 (1), p.27-41 |
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| language | eng |
| recordid | cdi_gale_infotracmisc_A241947523 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Administration, Oral Adult Age Factors Aged Aged, 80 and over Drug therapy Humans Imidazoles - administration & dosage Imidazoles - adverse effects Imidazoles - pharmacokinetics Impotence Internal Medicine Male Medicine Medicine & Public Health Middle Aged Original Research Article Pharmacokinetics Pharmacology/Toxicology Pharmacotherapy Phosphodiesterase 5 Inhibitors - administration & dosage Phosphodiesterase 5 Inhibitors - adverse effects Phosphodiesterase 5 Inhibitors - pharmacokinetics Piperazines - administration & dosage Piperazines - adverse effects Piperazines - pharmacokinetics Sulfones - administration & dosage Sulfones - adverse effects Sulfones - pharmacokinetics Tablets - administration & dosage Triazines - administration & dosage Triazines - adverse effects Triazines - pharmacokinetics Vardenafil Dihydrochloride |
| title | Pharmacokinetics of a New Orodispersible Tablet Formulation of Vardenafil: Results of Three Clinical Trials |
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