Effects of Atazanavir/Ritonavir or Fosamprenavir/Ritonavir on the Pharmacokinetics of Rosuvastatin
BACKGROUND:Rosuvastatin (RSV) is a potent statin with a lower potential for drug interactions. However, recent data have revealed unexpected increases in RSV concentrations with lopinavir/ritonavir. The objective is to study the pharmacokinetic interaction of RSV with atazanavir/ritonavir (ATV/RTV)...
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| Veröffentlicht in: | Journal of cardiovascular pharmacology 2008-06, Vol.51 (6), p.605-610 |
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| container_title | Journal of cardiovascular pharmacology |
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| creator | Busti, Anthony J Bain, Amy M Hall, Ronald G Bedimo, Roger G Leff, Richard D Meek, Claudia Mehvar, Reza |
| description | BACKGROUND:Rosuvastatin (RSV) is a potent statin with a lower potential for drug interactions. However, recent data have revealed unexpected increases in RSV concentrations with lopinavir/ritonavir. The objective is to study the pharmacokinetic interaction of RSV with atazanavir/ritonavir (ATV/RTV) or fosamprenavir/ritonavir (FPV/RTV).
METHODS:In a prospective pharmacokinetic drug interaction study, six HIV-seronegative, healthy adult volunteers received single 10-mg doses of RSV at baseline and after 6 days of ATV/RTV and FPV/RTV, with 6-day washout periods. Plasma concentrations of RSV and its metabolites, N-desmethyl-RSV and RSV-lactone, were measured by using a internally validated tandem mass spectrometric (LC-MS/MS) method over 24 hours.
RESULTS:Compared to baseline, the area under the plasma concentration-time curve (AUC0-24h) and maximum plasma concentration (Cmax) of RSV increased by 213% and 600%, respectively, and the time to reach Cmax was shorter (1.75 h vs. 2.91 h) when given with ATV/RTV (P < 0.05). However, coadministration with FPV/RTV did not significantly affect the pharmacokinetics of RSV. The AUC0-24h of N-desmethyl-RSV was not significantly affected by either combinations, but that of RSV-lactone increased (P < 0.05) by 61% and 76% after coadministration with ATV/RTV and FPV/RTV, respectively.
CONCLUSION:ATV/RTV significantly increases the plasma concentrations of rosuvastatin, most likely by increasing rosuvastatinʼs oral bioavailability. Dose limitations of RSV with ATV/RTV may be needed. |
| doi_str_mv | 10.1097/FJC.0b013e31817b5b5a |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1097_FJC_0b013e31817b5b5a</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>18520949</sourcerecordid><originalsourceid>FETCH-LOGICAL-c466a-542ec68c29f4317e01de098a189148fe7bd01e029d940775d24b1024ef7953463</originalsourceid><addsrcrecordid>eNp9kNtKw0AURQdRbK3-gUh-IO2ZWybzWErrhYJS9DlMkjMkNmnKzLRFv97aFgQFn86Gs9d-WITcUhhS0Go0e5oMIQfKkdOUqlzm0pyRPpWcxwIYPyd9oAnETIikR668fwegQqrkkvRoKhloofskn1qLRfBRZ6NxMJ9mZba1Gy3q0B1S1Llo1nnTrh3-ea2iUGH0UhnXmqJb1isMdXGYWnR-szU-mFCvrsmFNY3Hm9MdkLfZ9HXyEM-f7x8n43lciCQxsRQMiyQtmLaCU4VASwSdGppqKlKLKi-BIjBdagFKyZKJnAITaJWWXCR8QMRxt3Cd9w5ttnZ1a9xHRiH7VpbtlWW_le2xuyO23uQtlj_QydG-kB4Lu64J6Pyy2ezQZRWaJlT_b38B2n97vQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Effects of Atazanavir/Ritonavir or Fosamprenavir/Ritonavir on the Pharmacokinetics of Rosuvastatin</title><source>MEDLINE</source><source>Journals@Ovid LWW Legacy Archive</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Journals@Ovid Complete</source><creator>Busti, Anthony J ; Bain, Amy M ; Hall, Ronald G ; Bedimo, Roger G ; Leff, Richard D ; Meek, Claudia ; Mehvar, Reza</creator><creatorcontrib>Busti, Anthony J ; Bain, Amy M ; Hall, Ronald G ; Bedimo, Roger G ; Leff, Richard D ; Meek, Claudia ; Mehvar, Reza</creatorcontrib><description>BACKGROUND:Rosuvastatin (RSV) is a potent statin with a lower potential for drug interactions. However, recent data have revealed unexpected increases in RSV concentrations with lopinavir/ritonavir. The objective is to study the pharmacokinetic interaction of RSV with atazanavir/ritonavir (ATV/RTV) or fosamprenavir/ritonavir (FPV/RTV).
METHODS:In a prospective pharmacokinetic drug interaction study, six HIV-seronegative, healthy adult volunteers received single 10-mg doses of RSV at baseline and after 6 days of ATV/RTV and FPV/RTV, with 6-day washout periods. Plasma concentrations of RSV and its metabolites, N-desmethyl-RSV and RSV-lactone, were measured by using a internally validated tandem mass spectrometric (LC-MS/MS) method over 24 hours.
RESULTS:Compared to baseline, the area under the plasma concentration-time curve (AUC0-24h) and maximum plasma concentration (Cmax) of RSV increased by 213% and 600%, respectively, and the time to reach Cmax was shorter (1.75 h vs. 2.91 h) when given with ATV/RTV (P < 0.05). However, coadministration with FPV/RTV did not significantly affect the pharmacokinetics of RSV. The AUC0-24h of N-desmethyl-RSV was not significantly affected by either combinations, but that of RSV-lactone increased (P < 0.05) by 61% and 76% after coadministration with ATV/RTV and FPV/RTV, respectively.
CONCLUSION:ATV/RTV significantly increases the plasma concentrations of rosuvastatin, most likely by increasing rosuvastatinʼs oral bioavailability. Dose limitations of RSV with ATV/RTV may be needed.</description><identifier>ISSN: 0160-2446</identifier><identifier>EISSN: 1533-4023</identifier><identifier>DOI: 10.1097/FJC.0b013e31817b5b5a</identifier><identifier>PMID: 18520949</identifier><language>eng</language><publisher>United States: Lippincott Williams & Wilkins, Inc</publisher><subject>Adult ; Anti-HIV Agents - pharmacology ; Area Under Curve ; Atazanavir Sulfate ; Carbamates - pharmacology ; Drug Combinations ; Drug Interactions ; Female ; Fluorobenzenes - blood ; Fluorobenzenes - pharmacokinetics ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - blood ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics ; Male ; Oligopeptides - pharmacology ; Organophosphates - pharmacology ; Prospective Studies ; Pyridines - pharmacology ; Pyrimidines - blood ; Pyrimidines - pharmacokinetics ; Ritonavir - pharmacology ; Rosuvastatin Calcium ; Sulfonamides - blood ; Sulfonamides - pharmacokinetics ; Sulfonamides - pharmacology</subject><ispartof>Journal of cardiovascular pharmacology, 2008-06, Vol.51 (6), p.605-610</ispartof><rights>2008 Lippincott Williams & Wilkins, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c466a-542ec68c29f4317e01de098a189148fe7bd01e029d940775d24b1024ef7953463</citedby><cites>FETCH-LOGICAL-c466a-542ec68c29f4317e01de098a189148fe7bd01e029d940775d24b1024ef7953463</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18520949$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Busti, Anthony J</creatorcontrib><creatorcontrib>Bain, Amy M</creatorcontrib><creatorcontrib>Hall, Ronald G</creatorcontrib><creatorcontrib>Bedimo, Roger G</creatorcontrib><creatorcontrib>Leff, Richard D</creatorcontrib><creatorcontrib>Meek, Claudia</creatorcontrib><creatorcontrib>Mehvar, Reza</creatorcontrib><title>Effects of Atazanavir/Ritonavir or Fosamprenavir/Ritonavir on the Pharmacokinetics of Rosuvastatin</title><title>Journal of cardiovascular pharmacology</title><addtitle>J Cardiovasc Pharmacol</addtitle><description>BACKGROUND:Rosuvastatin (RSV) is a potent statin with a lower potential for drug interactions. However, recent data have revealed unexpected increases in RSV concentrations with lopinavir/ritonavir. The objective is to study the pharmacokinetic interaction of RSV with atazanavir/ritonavir (ATV/RTV) or fosamprenavir/ritonavir (FPV/RTV).
METHODS:In a prospective pharmacokinetic drug interaction study, six HIV-seronegative, healthy adult volunteers received single 10-mg doses of RSV at baseline and after 6 days of ATV/RTV and FPV/RTV, with 6-day washout periods. Plasma concentrations of RSV and its metabolites, N-desmethyl-RSV and RSV-lactone, were measured by using a internally validated tandem mass spectrometric (LC-MS/MS) method over 24 hours.
RESULTS:Compared to baseline, the area under the plasma concentration-time curve (AUC0-24h) and maximum plasma concentration (Cmax) of RSV increased by 213% and 600%, respectively, and the time to reach Cmax was shorter (1.75 h vs. 2.91 h) when given with ATV/RTV (P < 0.05). However, coadministration with FPV/RTV did not significantly affect the pharmacokinetics of RSV. The AUC0-24h of N-desmethyl-RSV was not significantly affected by either combinations, but that of RSV-lactone increased (P < 0.05) by 61% and 76% after coadministration with ATV/RTV and FPV/RTV, respectively.
CONCLUSION:ATV/RTV significantly increases the plasma concentrations of rosuvastatin, most likely by increasing rosuvastatinʼs oral bioavailability. Dose limitations of RSV with ATV/RTV may be needed.</description><subject>Adult</subject><subject>Anti-HIV Agents - pharmacology</subject><subject>Area Under Curve</subject><subject>Atazanavir Sulfate</subject><subject>Carbamates - pharmacology</subject><subject>Drug Combinations</subject><subject>Drug Interactions</subject><subject>Female</subject><subject>Fluorobenzenes - blood</subject><subject>Fluorobenzenes - pharmacokinetics</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - blood</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics</subject><subject>Male</subject><subject>Oligopeptides - pharmacology</subject><subject>Organophosphates - pharmacology</subject><subject>Prospective Studies</subject><subject>Pyridines - pharmacology</subject><subject>Pyrimidines - blood</subject><subject>Pyrimidines - pharmacokinetics</subject><subject>Ritonavir - pharmacology</subject><subject>Rosuvastatin Calcium</subject><subject>Sulfonamides - blood</subject><subject>Sulfonamides - pharmacokinetics</subject><subject>Sulfonamides - pharmacology</subject><issn>0160-2446</issn><issn>1533-4023</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kNtKw0AURQdRbK3-gUh-IO2ZWybzWErrhYJS9DlMkjMkNmnKzLRFv97aFgQFn86Gs9d-WITcUhhS0Go0e5oMIQfKkdOUqlzm0pyRPpWcxwIYPyd9oAnETIikR668fwegQqrkkvRoKhloofskn1qLRfBRZ6NxMJ9mZba1Gy3q0B1S1Llo1nnTrh3-ea2iUGH0UhnXmqJb1isMdXGYWnR-szU-mFCvrsmFNY3Hm9MdkLfZ9HXyEM-f7x8n43lciCQxsRQMiyQtmLaCU4VASwSdGppqKlKLKi-BIjBdagFKyZKJnAITaJWWXCR8QMRxt3Cd9w5ttnZ1a9xHRiH7VpbtlWW_le2xuyO23uQtlj_QydG-kB4Lu64J6Pyy2ezQZRWaJlT_b38B2n97vQ</recordid><startdate>200806</startdate><enddate>200806</enddate><creator>Busti, Anthony J</creator><creator>Bain, Amy M</creator><creator>Hall, Ronald G</creator><creator>Bedimo, Roger G</creator><creator>Leff, Richard D</creator><creator>Meek, Claudia</creator><creator>Mehvar, Reza</creator><general>Lippincott Williams & Wilkins, 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>200806</creationdate><title>Effects of Atazanavir/Ritonavir or Fosamprenavir/Ritonavir on the Pharmacokinetics of Rosuvastatin</title><author>Busti, Anthony J ; Bain, Amy M ; Hall, Ronald G ; Bedimo, Roger G ; Leff, Richard D ; Meek, Claudia ; Mehvar, Reza</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c466a-542ec68c29f4317e01de098a189148fe7bd01e029d940775d24b1024ef7953463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adult</topic><topic>Anti-HIV Agents - pharmacology</topic><topic>Area Under Curve</topic><topic>Atazanavir Sulfate</topic><topic>Carbamates - pharmacology</topic><topic>Drug Combinations</topic><topic>Drug Interactions</topic><topic>Female</topic><topic>Fluorobenzenes - blood</topic><topic>Fluorobenzenes - pharmacokinetics</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - blood</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics</topic><topic>Male</topic><topic>Oligopeptides - pharmacology</topic><topic>Organophosphates - pharmacology</topic><topic>Prospective Studies</topic><topic>Pyridines - pharmacology</topic><topic>Pyrimidines - blood</topic><topic>Pyrimidines - pharmacokinetics</topic><topic>Ritonavir - pharmacology</topic><topic>Rosuvastatin Calcium</topic><topic>Sulfonamides - blood</topic><topic>Sulfonamides - pharmacokinetics</topic><topic>Sulfonamides - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Busti, Anthony J</creatorcontrib><creatorcontrib>Bain, Amy M</creatorcontrib><creatorcontrib>Hall, Ronald G</creatorcontrib><creatorcontrib>Bedimo, Roger G</creatorcontrib><creatorcontrib>Leff, Richard D</creatorcontrib><creatorcontrib>Meek, Claudia</creatorcontrib><creatorcontrib>Mehvar, Reza</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of cardiovascular pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Busti, Anthony J</au><au>Bain, Amy M</au><au>Hall, Ronald G</au><au>Bedimo, Roger G</au><au>Leff, Richard D</au><au>Meek, Claudia</au><au>Mehvar, Reza</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Atazanavir/Ritonavir or Fosamprenavir/Ritonavir on the Pharmacokinetics of Rosuvastatin</atitle><jtitle>Journal of cardiovascular pharmacology</jtitle><addtitle>J Cardiovasc Pharmacol</addtitle><date>2008-06</date><risdate>2008</risdate><volume>51</volume><issue>6</issue><spage>605</spage><epage>610</epage><pages>605-610</pages><issn>0160-2446</issn><eissn>1533-4023</eissn><abstract>BACKGROUND:Rosuvastatin (RSV) is a potent statin with a lower potential for drug interactions. However, recent data have revealed unexpected increases in RSV concentrations with lopinavir/ritonavir. The objective is to study the pharmacokinetic interaction of RSV with atazanavir/ritonavir (ATV/RTV) or fosamprenavir/ritonavir (FPV/RTV).
METHODS:In a prospective pharmacokinetic drug interaction study, six HIV-seronegative, healthy adult volunteers received single 10-mg doses of RSV at baseline and after 6 days of ATV/RTV and FPV/RTV, with 6-day washout periods. Plasma concentrations of RSV and its metabolites, N-desmethyl-RSV and RSV-lactone, were measured by using a internally validated tandem mass spectrometric (LC-MS/MS) method over 24 hours.
RESULTS:Compared to baseline, the area under the plasma concentration-time curve (AUC0-24h) and maximum plasma concentration (Cmax) of RSV increased by 213% and 600%, respectively, and the time to reach Cmax was shorter (1.75 h vs. 2.91 h) when given with ATV/RTV (P < 0.05). However, coadministration with FPV/RTV did not significantly affect the pharmacokinetics of RSV. The AUC0-24h of N-desmethyl-RSV was not significantly affected by either combinations, but that of RSV-lactone increased (P < 0.05) by 61% and 76% after coadministration with ATV/RTV and FPV/RTV, respectively.
CONCLUSION:ATV/RTV significantly increases the plasma concentrations of rosuvastatin, most likely by increasing rosuvastatinʼs oral bioavailability. Dose limitations of RSV with ATV/RTV may be needed.</abstract><cop>United States</cop><pub>Lippincott Williams & Wilkins, Inc</pub><pmid>18520949</pmid><doi>10.1097/FJC.0b013e31817b5b5a</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0160-2446 |
| ispartof | Journal of cardiovascular pharmacology, 2008-06, Vol.51 (6), p.605-610 |
| issn | 0160-2446 1533-4023 |
| language | eng |
| recordid | cdi_crossref_primary_10_1097_FJC_0b013e31817b5b5a |
| source | MEDLINE; Journals@Ovid LWW Legacy Archive; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete |
| subjects | Adult Anti-HIV Agents - pharmacology Area Under Curve Atazanavir Sulfate Carbamates - pharmacology Drug Combinations Drug Interactions Female Fluorobenzenes - blood Fluorobenzenes - pharmacokinetics Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - blood Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics Male Oligopeptides - pharmacology Organophosphates - pharmacology Prospective Studies Pyridines - pharmacology Pyrimidines - blood Pyrimidines - pharmacokinetics Ritonavir - pharmacology Rosuvastatin Calcium Sulfonamides - blood Sulfonamides - pharmacokinetics Sulfonamides - pharmacology |
| title | Effects of Atazanavir/Ritonavir or Fosamprenavir/Ritonavir on the Pharmacokinetics of Rosuvastatin |
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