The pharmacokinetics of dronedarone in normolipidemic and hyperlipidemic rats
The objectives of the current study were to characterize the pharmacokinetic profile of dronedarone in the rat, and to examine the effect of hyperlipidemia on its pharmacokinetics. Single doses of dronedarone were administered to rats intravenously (4 mg/kg), orally (55 mg/kg) and intraperitoneally...
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| Veröffentlicht in: | Biopharmaceutics & drug disposition 2016-09, Vol.37 (6), p.345-351 |
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| creator | Jardan, Yousef A. Bin Brocks, Dion R. |
| description | The objectives of the current study were to characterize the pharmacokinetic profile of dronedarone in the rat, and to examine the effect of hyperlipidemia on its pharmacokinetics. Single doses of dronedarone were administered to rats intravenously (4 mg/kg), orally (55 mg/kg) and intraperitoneally (65 mg/kg). To induce hyperlipidemia, some of the rats were administered intraperitoneal doses of poloxamer 407 before giving an oral dose of dronedarone. After intravenous doses of 4 mg/kg dronedarone, plasma clearance and volume of distribution at steady‐state were 25.1 ± 8.09 mL/min/kg and 10.8 ± 4.77 L/kg, respectively. After oral doses the maximum plasma concentrations (Cmax) and their median time of attainment (tmax) were 1.87 ± 1.65 mg/mL and 3.5 h, respectively. Intraperitoneal administration of 65 mg/kg dronedarone base yielded plasma Cmax and median tmax of 0.816 ± 0.611 mg/mL and 3 h, respectively. Protein binding was high in NL and HL plasma. Dronedarone is extensively distributed with high volume of distribution in the rat. The drug showed poor bioavailability ( |
| doi_str_mv | 10.1002/bdd.2016 |
| format | Article |
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Bin ; Brocks, Dion R.</creator><creatorcontrib>Jardan, Yousef A. Bin ; Brocks, Dion R.</creatorcontrib><description>The objectives of the current study were to characterize the pharmacokinetic profile of dronedarone in the rat, and to examine the effect of hyperlipidemia on its pharmacokinetics. Single doses of dronedarone were administered to rats intravenously (4 mg/kg), orally (55 mg/kg) and intraperitoneally (65 mg/kg). To induce hyperlipidemia, some of the rats were administered intraperitoneal doses of poloxamer 407 before giving an oral dose of dronedarone. After intravenous doses of 4 mg/kg dronedarone, plasma clearance and volume of distribution at steady‐state were 25.1 ± 8.09 mL/min/kg and 10.8 ± 4.77 L/kg, respectively. After oral doses the maximum plasma concentrations (Cmax) and their median time of attainment (tmax) were 1.87 ± 1.65 mg/mL and 3.5 h, respectively. Intraperitoneal administration of 65 mg/kg dronedarone base yielded plasma Cmax and median tmax of 0.816 ± 0.611 mg/mL and 3 h, respectively. Protein binding was high in NL and HL plasma. Dronedarone is extensively distributed with high volume of distribution in the rat. The drug showed poor bioavailability (<20%) after oral and intraperitoneal administration. The increased plasma concentrations after oral dosing to hyperlipidemic rats appears to be attributable to a direct effect on metabolizing enzymes or transport proteins. 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Bin</creatorcontrib><creatorcontrib>Brocks, Dion R.</creatorcontrib><title>The pharmacokinetics of dronedarone in normolipidemic and hyperlipidemic rats</title><title>Biopharmaceutics & drug disposition</title><addtitle>Biopharm. Drug Dispos</addtitle><description>The objectives of the current study were to characterize the pharmacokinetic profile of dronedarone in the rat, and to examine the effect of hyperlipidemia on its pharmacokinetics. Single doses of dronedarone were administered to rats intravenously (4 mg/kg), orally (55 mg/kg) and intraperitoneally (65 mg/kg). To induce hyperlipidemia, some of the rats were administered intraperitoneal doses of poloxamer 407 before giving an oral dose of dronedarone. After intravenous doses of 4 mg/kg dronedarone, plasma clearance and volume of distribution at steady‐state were 25.1 ± 8.09 mL/min/kg and 10.8 ± 4.77 L/kg, respectively. After oral doses the maximum plasma concentrations (Cmax) and their median time of attainment (tmax) were 1.87 ± 1.65 mg/mL and 3.5 h, respectively. Intraperitoneal administration of 65 mg/kg dronedarone base yielded plasma Cmax and median tmax of 0.816 ± 0.611 mg/mL and 3 h, respectively. Protein binding was high in NL and HL plasma. Dronedarone is extensively distributed with high volume of distribution in the rat. The drug showed poor bioavailability (<20%) after oral and intraperitoneal administration. The increased plasma concentrations after oral dosing to hyperlipidemic rats appears to be attributable to a direct effect on metabolizing enzymes or transport proteins. Copyright © 2016 John Wiley & Sons, Ltd.</description><subject>absolute bioavailability</subject><subject>Administration, Intravenous</subject><subject>Administration, Oral</subject><subject>amiodarone</subject><subject>Amiodarone - administration & dosage</subject><subject>Amiodarone - analogs & derivatives</subject><subject>Amiodarone - blood</subject><subject>Amiodarone - pharmacokinetics</subject><subject>Animals</subject><subject>Anti-Arrhythmia Agents - administration & dosage</subject><subject>Anti-Arrhythmia Agents - blood</subject><subject>Anti-Arrhythmia Agents - pharmacokinetics</subject><subject>antiarrhythmic</subject><subject>Area Under Curve</subject><subject>Benzofuran</subject><subject>Biological Availability</subject><subject>Hyperlipidemias - chemically induced</subject><subject>Hyperlipidemias - metabolism</subject><subject>Injections, Intraperitoneal</subject><subject>Male</subject><subject>Poloxamer</subject><subject>poloxamer 407</subject><subject>Protein Binding</subject><subject>Rats, Sprague-Dawley</subject><issn>0142-2782</issn><issn>1099-081X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10F1LHDEYhuFQlLrVQn9BGfCkJ6N5k0wyc6jrRwU_ULR6FpLJO2x0ZjJNdrH77zuLq4LgSQLh4iY8hPwAugeUsn3r3B6jIL-QCdCqymkJDxtkQkGwnKmSbZFvKT1SSiUAfCVbTEEleKUm5OJ2htkwM7EzdXjyPc59nbLQZC6GHp1ZnZnvsz7ELrR-8A47X2emd9lsOWB8f4pmnnbIZmPahN_X9za5Ozm-nf7Oz69Oz6YH53nNSyVzCVZB0VhnWVFzKGQjQJUlGluzSlQowKkSG8us4dIxZoByR22hGobCsJJvk18v3SGGvwtMc935VGPbmh7DImkoQVEhRVWNdPcDfQyL2I-_WylZSFCCvwfrGFKK2Ogh-s7EpQaqVxPrcWK9mnikP9fBhe3QvcHXTUeQv4Bn3-Ly05A-PDpaB9fepzn-e_MmPmmpuCr0_eWpZifTw-ubKdd_-H8h6JNV</recordid><startdate>201609</startdate><enddate>201609</enddate><creator>Jardan, Yousef A. 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Bin ; Brocks, Dion R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3876-61b715fbdb25c3156f41788eabc2949e41d78efb2ba36d22a103d0b57f2e4a283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>absolute bioavailability</topic><topic>Administration, Intravenous</topic><topic>Administration, Oral</topic><topic>amiodarone</topic><topic>Amiodarone - administration & dosage</topic><topic>Amiodarone - analogs & derivatives</topic><topic>Amiodarone - blood</topic><topic>Amiodarone - pharmacokinetics</topic><topic>Animals</topic><topic>Anti-Arrhythmia Agents - administration & dosage</topic><topic>Anti-Arrhythmia Agents - blood</topic><topic>Anti-Arrhythmia Agents - pharmacokinetics</topic><topic>antiarrhythmic</topic><topic>Area Under Curve</topic><topic>Benzofuran</topic><topic>Biological Availability</topic><topic>Hyperlipidemias - chemically induced</topic><topic>Hyperlipidemias - metabolism</topic><topic>Injections, Intraperitoneal</topic><topic>Male</topic><topic>Poloxamer</topic><topic>poloxamer 407</topic><topic>Protein Binding</topic><topic>Rats, Sprague-Dawley</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jardan, Yousef A. 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Bin</au><au>Brocks, Dion R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The pharmacokinetics of dronedarone in normolipidemic and hyperlipidemic rats</atitle><jtitle>Biopharmaceutics & drug disposition</jtitle><addtitle>Biopharm. Drug Dispos</addtitle><date>2016-09</date><risdate>2016</risdate><volume>37</volume><issue>6</issue><spage>345</spage><epage>351</epage><pages>345-351</pages><issn>0142-2782</issn><eissn>1099-081X</eissn><coden>BDDID8</coden><abstract>The objectives of the current study were to characterize the pharmacokinetic profile of dronedarone in the rat, and to examine the effect of hyperlipidemia on its pharmacokinetics. Single doses of dronedarone were administered to rats intravenously (4 mg/kg), orally (55 mg/kg) and intraperitoneally (65 mg/kg). To induce hyperlipidemia, some of the rats were administered intraperitoneal doses of poloxamer 407 before giving an oral dose of dronedarone. After intravenous doses of 4 mg/kg dronedarone, plasma clearance and volume of distribution at steady‐state were 25.1 ± 8.09 mL/min/kg and 10.8 ± 4.77 L/kg, respectively. After oral doses the maximum plasma concentrations (Cmax) and their median time of attainment (tmax) were 1.87 ± 1.65 mg/mL and 3.5 h, respectively. Intraperitoneal administration of 65 mg/kg dronedarone base yielded plasma Cmax and median tmax of 0.816 ± 0.611 mg/mL and 3 h, respectively. Protein binding was high in NL and HL plasma. Dronedarone is extensively distributed with high volume of distribution in the rat. The drug showed poor bioavailability (<20%) after oral and intraperitoneal administration. The increased plasma concentrations after oral dosing to hyperlipidemic rats appears to be attributable to a direct effect on metabolizing enzymes or transport proteins. Copyright © 2016 John Wiley & Sons, Ltd.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>27194397</pmid><doi>10.1002/bdd.2016</doi><tpages>7</tpages></addata></record> |
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| subjects | absolute bioavailability Administration, Intravenous Administration, Oral amiodarone Amiodarone - administration & dosage Amiodarone - analogs & derivatives Amiodarone - blood Amiodarone - pharmacokinetics Animals Anti-Arrhythmia Agents - administration & dosage Anti-Arrhythmia Agents - blood Anti-Arrhythmia Agents - pharmacokinetics antiarrhythmic Area Under Curve Benzofuran Biological Availability Hyperlipidemias - chemically induced Hyperlipidemias - metabolism Injections, Intraperitoneal Male Poloxamer poloxamer 407 Protein Binding Rats, Sprague-Dawley |
| title | The pharmacokinetics of dronedarone in normolipidemic and hyperlipidemic rats |
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