Pharmacokinetic profile of a modified release formulation of trimetazidine (TMZ MR 35 mg) in the elderly and patients with renal failure
Objectives – To study the effect of age and renal function on the pharmacokinetic profile of a modified release tablet of trimetazidine (TMZ MR 35 mg) administered twice daily. Methods– Study 1: Twelve healthy elderly subjects (CLcreat 72±8 ml/min, 72±4 years mean±SD) and eight young volunteers (CLc...
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| Veröffentlicht in: | Biopharmaceutics & drug disposition 2003-05, Vol.24 (4), p.159-164 |
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| creator | Barré, J. Ledudal, P. Oosterhuis, B. Brakenhoff, J.P.G. Wilkens, G. Sollie, F.A.E. Tran, D. |
| description | Objectives – To study the effect of age and renal function on the pharmacokinetic profile of a modified release tablet of trimetazidine (TMZ MR 35 mg) administered twice daily.
Methods– Study 1: Twelve healthy elderly subjects (CLcreat 72±8 ml/min, 72±4 years mean±SD) and eight young volunteers (CLcreat 134±18 ml/min, 25±8 years) received TMZ MR 35 mg b.i.d. (eight doses). Study 2: eight patients with severe renal failure (CLcreat. 17±5 ml/min, 54±10 years), five patients with moderate renal failure (CLcreat. 39±6 ml/min, 54±15 years) and eight volunteers (CLcreat. 104±17 ml/min, 53±9 years) received TMZ MR 35 mg b.i.d. (patients: ten doses, volunteers: eight doses). Serial blood and urine samples were obtained following administration of the last dose in each study. TMZ plasma and urine concentrations were determined by gas chromatography (NPD‐detector). The resulting data were analysed using standard non‐compartmental pharmacokinetic methods.
Results– Study 1: Elimination half‐life of TMZ was significantly longer and renal clearance significantly lower in the elderly subjects. Study 2: In patients with either moderate or severe renal failure, exposure (AUC0–24) was significantly increased and renal clearance (CLR) was significantly decreased. Significant correlations were observed between CLcreat and CLR (r=0.94) and between CLcreat and AUC0–24 (r=−0.94).
Conclusion – With repeated administration of TMZ MR 35 mg b.i.d., a decrease in CLcreat is directly related to a decrease in CLR and results in an increase in exposure to TMZ. Copyright © 2003 John Wiley & Sons, Ltd. |
| doi_str_mv | 10.1002/bdd.350 |
| format | Article |
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Methods– Study 1: Twelve healthy elderly subjects (CLcreat 72±8 ml/min, 72±4 years mean±SD) and eight young volunteers (CLcreat 134±18 ml/min, 25±8 years) received TMZ MR 35 mg b.i.d. (eight doses). Study 2: eight patients with severe renal failure (CLcreat. 17±5 ml/min, 54±10 years), five patients with moderate renal failure (CLcreat. 39±6 ml/min, 54±15 years) and eight volunteers (CLcreat. 104±17 ml/min, 53±9 years) received TMZ MR 35 mg b.i.d. (patients: ten doses, volunteers: eight doses). Serial blood and urine samples were obtained following administration of the last dose in each study. TMZ plasma and urine concentrations were determined by gas chromatography (NPD‐detector). The resulting data were analysed using standard non‐compartmental pharmacokinetic methods.
Results– Study 1: Elimination half‐life of TMZ was significantly longer and renal clearance significantly lower in the elderly subjects. Study 2: In patients with either moderate or severe renal failure, exposure (AUC0–24) was significantly increased and renal clearance (CLR) was significantly decreased. Significant correlations were observed between CLcreat and CLR (r=0.94) and between CLcreat and AUC0–24 (r=−0.94).
Conclusion – With repeated administration of TMZ MR 35 mg b.i.d., a decrease in CLcreat is directly related to a decrease in CLR and results in an increase in exposure to TMZ. Copyright © 2003 John Wiley & Sons, Ltd.</description><identifier>ISSN: 0142-2782</identifier><identifier>EISSN: 1099-081X</identifier><identifier>DOI: 10.1002/bdd.350</identifier><identifier>PMID: 12698499</identifier><identifier>CODEN: BDDID8</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Adolescent ; Adult ; Age Factors ; Aged ; Aging - metabolism ; Antianginal agents. Coronary vasodilator agents ; Biological and medical sciences ; Cardiovascular system ; Delayed-Action Preparations ; Drug Administration Schedule ; elderly ; Female ; Humans ; Male ; Medical sciences ; Middle Aged ; pharmacokinetics ; Pharmacology. Drug treatments ; renal failure ; Renal Insufficiency - drug therapy ; Renal Insufficiency - physiopathology ; Tablets ; trimetazidine ; Trimetazidine - administration & dosage ; Trimetazidine - pharmacokinetics</subject><ispartof>Biopharmaceutics & drug disposition, 2003-05, Vol.24 (4), p.159-164</ispartof><rights>Copyright © 2003 John Wiley & Sons, Ltd.</rights><rights>2003 INIST-CNRS</rights><rights>Copyright 2003 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3810-e365778a34420ed6d29fbc3ed99ae1a7499e721d648e2909cc88549363bff9f3</citedby><cites>FETCH-LOGICAL-c3810-e365778a34420ed6d29fbc3ed99ae1a7499e721d648e2909cc88549363bff9f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fbdd.350$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fbdd.350$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14789341$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12698499$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Barré, J.</creatorcontrib><creatorcontrib>Ledudal, P.</creatorcontrib><creatorcontrib>Oosterhuis, B.</creatorcontrib><creatorcontrib>Brakenhoff, J.P.G.</creatorcontrib><creatorcontrib>Wilkens, G.</creatorcontrib><creatorcontrib>Sollie, F.A.E.</creatorcontrib><creatorcontrib>Tran, D.</creatorcontrib><title>Pharmacokinetic profile of a modified release formulation of trimetazidine (TMZ MR 35 mg) in the elderly and patients with renal failure</title><title>Biopharmaceutics & drug disposition</title><addtitle>Biopharm. Drug Dispos</addtitle><description>Objectives – To study the effect of age and renal function on the pharmacokinetic profile of a modified release tablet of trimetazidine (TMZ MR 35 mg) administered twice daily.
Methods– Study 1: Twelve healthy elderly subjects (CLcreat 72±8 ml/min, 72±4 years mean±SD) and eight young volunteers (CLcreat 134±18 ml/min, 25±8 years) received TMZ MR 35 mg b.i.d. (eight doses). Study 2: eight patients with severe renal failure (CLcreat. 17±5 ml/min, 54±10 years), five patients with moderate renal failure (CLcreat. 39±6 ml/min, 54±15 years) and eight volunteers (CLcreat. 104±17 ml/min, 53±9 years) received TMZ MR 35 mg b.i.d. (patients: ten doses, volunteers: eight doses). Serial blood and urine samples were obtained following administration of the last dose in each study. TMZ plasma and urine concentrations were determined by gas chromatography (NPD‐detector). The resulting data were analysed using standard non‐compartmental pharmacokinetic methods.
Results– Study 1: Elimination half‐life of TMZ was significantly longer and renal clearance significantly lower in the elderly subjects. Study 2: In patients with either moderate or severe renal failure, exposure (AUC0–24) was significantly increased and renal clearance (CLR) was significantly decreased. Significant correlations were observed between CLcreat and CLR (r=0.94) and between CLcreat and AUC0–24 (r=−0.94).
Conclusion – With repeated administration of TMZ MR 35 mg b.i.d., a decrease in CLcreat is directly related to a decrease in CLR and results in an increase in exposure to TMZ. Copyright © 2003 John Wiley & Sons, Ltd.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age Factors</subject><subject>Aged</subject><subject>Aging - metabolism</subject><subject>Antianginal agents. Coronary vasodilator agents</subject><subject>Biological and medical sciences</subject><subject>Cardiovascular system</subject><subject>Delayed-Action Preparations</subject><subject>Drug Administration Schedule</subject><subject>elderly</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>pharmacokinetics</subject><subject>Pharmacology. Drug treatments</subject><subject>renal failure</subject><subject>Renal Insufficiency - drug therapy</subject><subject>Renal Insufficiency - physiopathology</subject><subject>Tablets</subject><subject>trimetazidine</subject><subject>Trimetazidine - administration & dosage</subject><subject>Trimetazidine - pharmacokinetics</subject><issn>0142-2782</issn><issn>1099-081X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10c9u1DAQBnALgehSEG-AfOGfUIodZ2P7SFsoSC0gtBIVF2vWHrOmTrLYicryBDw2rrKiJ06-_OYbzWdCHnN2xBmrX6-dOxJLdocsONO6Yopf3iULxpu6qqWqD8iDnH8wxlrO-X1ywOtWq0brBfnzeQOpAztchR7HYOk2DT5EpIOnQLvBBR_Q0YQRISP1Q-qmCGMY-hsxptDhCL-DK9P0xeriG734QsWSdt9f0tDTcYMUo8MUdxR6R7dlEvsx0-swbkpoD5F6CHFK-JDc8xAzPtq_h2T17u3q5H11_unsw8mb88oKxVmFol1KqUA0Tc3Qta7Wfm0FOq0BOchyFMqau7ZRWGumrVVq2WjRirX32otD8myOLXf-nDCPpgvZYozQ4zBlIwXXbdEFPp-hTUPOCb3ZlmMh7Qxn5qZzUzo3pfMin-wjp3WH7tbtSy7g6R5AthB9gt6GfOsaqbRoeHGvZnddPmD3v33m-PR0XlvNOuQRf_3TkK5MK4Vcmq8fz4w8bjVXiplL8RfjRaY9</recordid><startdate>200305</startdate><enddate>200305</enddate><creator>Barré, J.</creator><creator>Ledudal, P.</creator><creator>Oosterhuis, B.</creator><creator>Brakenhoff, J.P.G.</creator><creator>Wilkens, G.</creator><creator>Sollie, F.A.E.</creator><creator>Tran, D.</creator><general>John Wiley & Sons, Ltd</general><general>Wiley</general><scope>BSCLL</scope><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>7X8</scope></search><sort><creationdate>200305</creationdate><title>Pharmacokinetic profile of a modified release formulation of trimetazidine (TMZ MR 35 mg) in the elderly and patients with renal failure</title><author>Barré, J. ; Ledudal, P. ; Oosterhuis, B. ; Brakenhoff, J.P.G. ; Wilkens, G. ; Sollie, F.A.E. ; Tran, D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3810-e365778a34420ed6d29fbc3ed99ae1a7499e721d648e2909cc88549363bff9f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age Factors</topic><topic>Aged</topic><topic>Aging - metabolism</topic><topic>Antianginal agents. Coronary vasodilator agents</topic><topic>Biological and medical sciences</topic><topic>Cardiovascular system</topic><topic>Delayed-Action Preparations</topic><topic>Drug Administration Schedule</topic><topic>elderly</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>pharmacokinetics</topic><topic>Pharmacology. Drug treatments</topic><topic>renal failure</topic><topic>Renal Insufficiency - drug therapy</topic><topic>Renal Insufficiency - physiopathology</topic><topic>Tablets</topic><topic>trimetazidine</topic><topic>Trimetazidine - administration & dosage</topic><topic>Trimetazidine - pharmacokinetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barré, J.</creatorcontrib><creatorcontrib>Ledudal, P.</creatorcontrib><creatorcontrib>Oosterhuis, B.</creatorcontrib><creatorcontrib>Brakenhoff, J.P.G.</creatorcontrib><creatorcontrib>Wilkens, G.</creatorcontrib><creatorcontrib>Sollie, F.A.E.</creatorcontrib><creatorcontrib>Tran, D.</creatorcontrib><collection>Istex</collection><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>MEDLINE - Academic</collection><jtitle>Biopharmaceutics & drug disposition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barré, J.</au><au>Ledudal, P.</au><au>Oosterhuis, B.</au><au>Brakenhoff, J.P.G.</au><au>Wilkens, G.</au><au>Sollie, F.A.E.</au><au>Tran, D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetic profile of a modified release formulation of trimetazidine (TMZ MR 35 mg) in the elderly and patients with renal failure</atitle><jtitle>Biopharmaceutics & drug disposition</jtitle><addtitle>Biopharm. Drug Dispos</addtitle><date>2003-05</date><risdate>2003</risdate><volume>24</volume><issue>4</issue><spage>159</spage><epage>164</epage><pages>159-164</pages><issn>0142-2782</issn><eissn>1099-081X</eissn><coden>BDDID8</coden><abstract>Objectives – To study the effect of age and renal function on the pharmacokinetic profile of a modified release tablet of trimetazidine (TMZ MR 35 mg) administered twice daily.
Methods– Study 1: Twelve healthy elderly subjects (CLcreat 72±8 ml/min, 72±4 years mean±SD) and eight young volunteers (CLcreat 134±18 ml/min, 25±8 years) received TMZ MR 35 mg b.i.d. (eight doses). Study 2: eight patients with severe renal failure (CLcreat. 17±5 ml/min, 54±10 years), five patients with moderate renal failure (CLcreat. 39±6 ml/min, 54±15 years) and eight volunteers (CLcreat. 104±17 ml/min, 53±9 years) received TMZ MR 35 mg b.i.d. (patients: ten doses, volunteers: eight doses). Serial blood and urine samples were obtained following administration of the last dose in each study. TMZ plasma and urine concentrations were determined by gas chromatography (NPD‐detector). The resulting data were analysed using standard non‐compartmental pharmacokinetic methods.
Results– Study 1: Elimination half‐life of TMZ was significantly longer and renal clearance significantly lower in the elderly subjects. Study 2: In patients with either moderate or severe renal failure, exposure (AUC0–24) was significantly increased and renal clearance (CLR) was significantly decreased. Significant correlations were observed between CLcreat and CLR (r=0.94) and between CLcreat and AUC0–24 (r=−0.94).
Conclusion – With repeated administration of TMZ MR 35 mg b.i.d., a decrease in CLcreat is directly related to a decrease in CLR and results in an increase in exposure to TMZ. Copyright © 2003 John Wiley & Sons, Ltd.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>12698499</pmid><doi>10.1002/bdd.350</doi><tpages>6</tpages></addata></record> |
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| subjects | Adolescent Adult Age Factors Aged Aging - metabolism Antianginal agents. Coronary vasodilator agents Biological and medical sciences Cardiovascular system Delayed-Action Preparations Drug Administration Schedule elderly Female Humans Male Medical sciences Middle Aged pharmacokinetics Pharmacology. Drug treatments renal failure Renal Insufficiency - drug therapy Renal Insufficiency - physiopathology Tablets trimetazidine Trimetazidine - administration & dosage Trimetazidine - pharmacokinetics |
| title | Pharmacokinetic profile of a modified release formulation of trimetazidine (TMZ MR 35 mg) in the elderly and patients with renal failure |
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