P-GLYCOPROTEIN SYSTEM AS A DETERMINANT OF DRUG INTERACTIONS: THE CASE OF DIGOXIN–VERAPAMIL
Digoxin, which has a very narrow therapeutic window, is one of the most commonly prescribed drugs in the treatment of congestive heart failure. In some cases of atrial fibrillation digoxin is used in combination with verapamil. Verapamil can increase the plasma concentration of digoxin up to 60–90%....
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| Veröffentlicht in: | Pharmacological research 1999-10, Vol.40 (4), p.301-306 |
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| creator | VERSCHRAAGEN, M. KOKS, C.H.W. SCHELLENS, J.H.M. BEIJNEN, J.H |
| description | Digoxin, which has a very narrow therapeutic window, is one of the most commonly prescribed drugs in the treatment of congestive heart failure. In some cases of atrial fibrillation digoxin is used in combination with verapamil. Verapamil can increase the plasma concentration of digoxin up to 60–90%. So far the precise mechanism of this pharmacokinetic drug–drug interaction is not known. Many studies suggest that verapamil reduces the renal clearance of digoxin. The energy-dependent membrane-bound transport enzyme, P-glycoprotein, may also be involved. Reports from oncology research show that verapamil can interact with P-glycoprotein as a modulator. Also taking into account that digoxin, like many anticancer drugs, is a substrate for P-glycoprotein, it is likely that P-glycoprotein modulation accounts for the digoxin–verapamil interaction. Current knowledge suggest that the non-competitive digoxin–verapamil interaction is due to inhibition of P-glycoprotein activity by verapamil resulting in a decreased renal tubular elimination of digoxin. |
| doi_str_mv | 10.1006/phrs.1999.0535 |
| format | Article |
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In some cases of atrial fibrillation digoxin is used in combination with verapamil. Verapamil can increase the plasma concentration of digoxin up to 60–90%. So far the precise mechanism of this pharmacokinetic drug–drug interaction is not known. Many studies suggest that verapamil reduces the renal clearance of digoxin. The energy-dependent membrane-bound transport enzyme, P-glycoprotein, may also be involved. Reports from oncology research show that verapamil can interact with P-glycoprotein as a modulator. Also taking into account that digoxin, like many anticancer drugs, is a substrate for P-glycoprotein, it is likely that P-glycoprotein modulation accounts for the digoxin–verapamil interaction. 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In some cases of atrial fibrillation digoxin is used in combination with verapamil. Verapamil can increase the plasma concentration of digoxin up to 60–90%. So far the precise mechanism of this pharmacokinetic drug–drug interaction is not known. Many studies suggest that verapamil reduces the renal clearance of digoxin. The energy-dependent membrane-bound transport enzyme, P-glycoprotein, may also be involved. Reports from oncology research show that verapamil can interact with P-glycoprotein as a modulator. Also taking into account that digoxin, like many anticancer drugs, is a substrate for P-glycoprotein, it is likely that P-glycoprotein modulation accounts for the digoxin–verapamil interaction. Current knowledge suggest that the non-competitive digoxin–verapamil interaction is due to inhibition of P-glycoprotein activity by verapamil resulting in a decreased renal tubular elimination of digoxin.</description><subject>Animals</subject><subject>Anti-Arrhythmia Agents - pharmacokinetics</subject><subject>Anti-Arrhythmia Agents - therapeutic use</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - drug effects</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism</subject><subject>Cardiotonic Agents - pharmacokinetics</subject><subject>Cardiotonic Agents - therapeutic use</subject><subject>Digoxin - blood</subject><subject>Digoxin - pharmacokinetics</subject><subject>Digoxin - therapeutic use</subject><subject>digoxin, verapamil, P-glycoprotein, interaction, multidrug resistance</subject><subject>Drug Interactions - physiology</subject><subject>Drug Resistance, Multiple - physiology</subject><subject>Heart Failure - drug therapy</subject><subject>Humans</subject><subject>Verapamil - pharmacokinetics</subject><subject>Verapamil - therapeutic use</subject><issn>1043-6618</issn><issn>1096-1186</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMFOg0AQhjdGY2v16tHsC4CzsLuw3gillIRCU9DYxGRDlyVirG2gmnjzHXxDn0QQD148zWTm-yeTD6FLAiYB4Nf7x6Y1iRDCBGazIzQmILhBiMuP-57aBufEHaGztn0CAEEJnKIRAWY5nMIYPSyNMF776XKV5kGU4Gyd5cECexn28DTIg9UiSrwkx-kMT1e3IY6Sbub5eZQm2Q3O5wH2vSz4WUdheh8lXx-fdx2x9BZRfI5OquK51Re_dYLyWZD7cyNOw8j3YkPZFA6Go91SFbawWAFcgWU7jGhVCKtilSCaEUZVAUwwyi1CBS8pL6hjg1XxzUa59gSZw1nV7Nq20ZXcN_W2aN4lAdlbkr0l2VuSvaUucDUE9q-brS7_4IOWDnAHQHdfv9W6ka2q9YvSZd1odZDlrv7v9jc8dm7y</recordid><startdate>19991001</startdate><enddate>19991001</enddate><creator>VERSCHRAAGEN, M.</creator><creator>KOKS, C.H.W.</creator><creator>SCHELLENS, J.H.M.</creator><creator>BEIJNEN, J.H</creator><general>Elsevier Ltd</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>19991001</creationdate><title>P-GLYCOPROTEIN SYSTEM AS A DETERMINANT OF DRUG INTERACTIONS: THE CASE OF DIGOXIN–VERAPAMIL</title><author>VERSCHRAAGEN, M. ; KOKS, C.H.W. ; SCHELLENS, J.H.M. ; BEIJNEN, J.H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c340t-7e8dca3925a06c023751eca92f5f91e5154ca05954621496d46a47302f6bbc83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Anti-Arrhythmia Agents - pharmacokinetics</topic><topic>Anti-Arrhythmia Agents - therapeutic use</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - drug effects</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism</topic><topic>Cardiotonic Agents - pharmacokinetics</topic><topic>Cardiotonic Agents - therapeutic use</topic><topic>Digoxin - blood</topic><topic>Digoxin - pharmacokinetics</topic><topic>Digoxin - therapeutic use</topic><topic>digoxin, verapamil, P-glycoprotein, interaction, multidrug resistance</topic><topic>Drug Interactions - physiology</topic><topic>Drug Resistance, Multiple - physiology</topic><topic>Heart Failure - drug therapy</topic><topic>Humans</topic><topic>Verapamil - pharmacokinetics</topic><topic>Verapamil - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>VERSCHRAAGEN, M.</creatorcontrib><creatorcontrib>KOKS, C.H.W.</creatorcontrib><creatorcontrib>SCHELLENS, J.H.M.</creatorcontrib><creatorcontrib>BEIJNEN, J.H</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Pharmacological research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>VERSCHRAAGEN, M.</au><au>KOKS, C.H.W.</au><au>SCHELLENS, J.H.M.</au><au>BEIJNEN, J.H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>P-GLYCOPROTEIN SYSTEM AS A DETERMINANT OF DRUG INTERACTIONS: THE CASE OF DIGOXIN–VERAPAMIL</atitle><jtitle>Pharmacological research</jtitle><addtitle>Pharmacol Res</addtitle><date>1999-10-01</date><risdate>1999</risdate><volume>40</volume><issue>4</issue><spage>301</spage><epage>306</epage><pages>301-306</pages><issn>1043-6618</issn><eissn>1096-1186</eissn><abstract>Digoxin, which has a very narrow therapeutic window, is one of the most commonly prescribed drugs in the treatment of congestive heart failure. In some cases of atrial fibrillation digoxin is used in combination with verapamil. Verapamil can increase the plasma concentration of digoxin up to 60–90%. So far the precise mechanism of this pharmacokinetic drug–drug interaction is not known. Many studies suggest that verapamil reduces the renal clearance of digoxin. The energy-dependent membrane-bound transport enzyme, P-glycoprotein, may also be involved. Reports from oncology research show that verapamil can interact with P-glycoprotein as a modulator. Also taking into account that digoxin, like many anticancer drugs, is a substrate for P-glycoprotein, it is likely that P-glycoprotein modulation accounts for the digoxin–verapamil interaction. Current knowledge suggest that the non-competitive digoxin–verapamil interaction is due to inhibition of P-glycoprotein activity by verapamil resulting in a decreased renal tubular elimination of digoxin.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>10527640</pmid><doi>10.1006/phrs.1999.0535</doi><tpages>6</tpages></addata></record> |
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| ispartof | Pharmacological research, 1999-10, Vol.40 (4), p.301-306 |
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| language | eng |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Animals Anti-Arrhythmia Agents - pharmacokinetics Anti-Arrhythmia Agents - therapeutic use ATP-Binding Cassette, Sub-Family B, Member 1 - drug effects ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism Cardiotonic Agents - pharmacokinetics Cardiotonic Agents - therapeutic use Digoxin - blood Digoxin - pharmacokinetics Digoxin - therapeutic use digoxin, verapamil, P-glycoprotein, interaction, multidrug resistance Drug Interactions - physiology Drug Resistance, Multiple - physiology Heart Failure - drug therapy Humans Verapamil - pharmacokinetics Verapamil - therapeutic use |
| title | P-GLYCOPROTEIN SYSTEM AS A DETERMINANT OF DRUG INTERACTIONS: THE CASE OF DIGOXIN–VERAPAMIL |
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