Reduced Elimination of Cyclosporine A in Elderly (>65 Years) Kidney Transplant Recipients
Physiologic functions that may affect pharmacokinetics of drugs are altered in elderly patients. The current study was performed to elucidate the effect of age on cyclosporine A (CsA) pharmacokinetics in renal transplant recipients. Twenty-five renal transplant recipients on CsA treatment were inclu...
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| Veröffentlicht in: | Transplantation 2008-11, Vol.86 (10), p.1379-1383 |
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| creator | FALCK, Pal ASBERG, Anders BYBERG, Karen-Therese BREMER, Sara BERGAN, Stein REUBSAET, Jan L. E MIDTVEDT, Karsten |
| description | Physiologic functions that may affect pharmacokinetics of drugs are altered in elderly patients. The current study was performed to elucidate the effect of age on cyclosporine A (CsA) pharmacokinetics in renal transplant recipients.
Twenty-five renal transplant recipients on CsA treatment were included in the study. CsA doses were adjusted by C2 monitoring. The patients were divided into two groups based on age; elderly: more than 65 years (n=11, mean 73 years) and younger: 18 to 64 years (n=14, mean 43 years). A full 12-hr pharmacokinetic profile was performed during stable phase. CsA whole blood and intracellular T-lymphocytes concentrations (first 6 hr) were measured. Genotyping of the CYP3A5*1/*3 and ABCB1 (C1236T, G2677T, C3435T) polymorphisms and quantification of whole blood mRNA ABCB1 expression were performed in all patients.
Elderly patients achieved target C2 levels with lower CsA doses than the younger patients (4.3+/-0.8 vs. 6.1+/-2.1 mg/day/kg, P=0.025) because of lower clearance of CsA (22.7+/-5.1 vs. 30.5+/-11.1 L/hr, P=0.031). Elderly patients also showed 44% higher intracellular-to-whole blood CsA ratio than younger patients (P=0.02). Neither the CYP3A5*1, the ABCB1 genotypes nor mRNA ABCB1 expression revealed any significant influence on CsA pharmacokinetics.
The clearance of CsA decreased with increasing age. In addition, elderly patients had a significant larger proportion of the whole blood CsA concentration located at the site of action (within T lymphocytes). This indicates that in elderly recipients it might be safe to aim for an even lower whole blood target levels than current guidelines propose. |
| doi_str_mv | 10.1097/TP.0b013e31818aa4b6 |
| format | Article |
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Twenty-five renal transplant recipients on CsA treatment were included in the study. CsA doses were adjusted by C2 monitoring. The patients were divided into two groups based on age; elderly: more than 65 years (n=11, mean 73 years) and younger: 18 to 64 years (n=14, mean 43 years). A full 12-hr pharmacokinetic profile was performed during stable phase. CsA whole blood and intracellular T-lymphocytes concentrations (first 6 hr) were measured. Genotyping of the CYP3A5*1/*3 and ABCB1 (C1236T, G2677T, C3435T) polymorphisms and quantification of whole blood mRNA ABCB1 expression were performed in all patients.
Elderly patients achieved target C2 levels with lower CsA doses than the younger patients (4.3+/-0.8 vs. 6.1+/-2.1 mg/day/kg, P=0.025) because of lower clearance of CsA (22.7+/-5.1 vs. 30.5+/-11.1 L/hr, P=0.031). Elderly patients also showed 44% higher intracellular-to-whole blood CsA ratio than younger patients (P=0.02). Neither the CYP3A5*1, the ABCB1 genotypes nor mRNA ABCB1 expression revealed any significant influence on CsA pharmacokinetics.
The clearance of CsA decreased with increasing age. In addition, elderly patients had a significant larger proportion of the whole blood CsA concentration located at the site of action (within T lymphocytes). This indicates that in elderly recipients it might be safe to aim for an even lower whole blood target levels than current guidelines propose.</description><identifier>ISSN: 0041-1337</identifier><identifier>EISSN: 1534-6080</identifier><identifier>DOI: 10.1097/TP.0b013e31818aa4b6</identifier><identifier>PMID: 19034006</identifier><identifier>CODEN: TRPLAU</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adolescent ; Adult ; Aged ; Aryl Hydrocarbon Hydroxylases - genetics ; ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics ; Biological and medical sciences ; Cyclosporine - adverse effects ; Cyclosporine - blood ; Cyclosporine - pharmacokinetics ; Cyclosporine - therapeutic use ; Cytochrome P-450 CYP2A6 ; Drug Administration Schedule ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Gene Expression Regulation ; Genotype ; Humans ; Immunosuppressive Agents - adverse effects ; Immunosuppressive Agents - blood ; Immunosuppressive Agents - pharmacokinetics ; Immunosuppressive Agents - therapeutic use ; Kidney Transplantation - immunology ; Kidney Transplantation - physiology ; Medical sciences ; Metabolic Clearance Rate ; Middle Aged ; Pilot Projects ; Prospective Studies ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; T-Lymphocytes - immunology ; Tissue, organ and graft immunology ; Young Adult</subject><ispartof>Transplantation, 2008-11, Vol.86 (10), p.1379-1383</ispartof><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-f9fdd02b50566c56a40a5900e75aac41f0ca50536bc80c7fda9120554743b5463</citedby><cites>FETCH-LOGICAL-c459t-f9fdd02b50566c56a40a5900e75aac41f0ca50536bc80c7fda9120554743b5463</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20904132$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19034006$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>FALCK, Pal</creatorcontrib><creatorcontrib>ASBERG, Anders</creatorcontrib><creatorcontrib>BYBERG, Karen-Therese</creatorcontrib><creatorcontrib>BREMER, Sara</creatorcontrib><creatorcontrib>BERGAN, Stein</creatorcontrib><creatorcontrib>REUBSAET, Jan L. E</creatorcontrib><creatorcontrib>MIDTVEDT, Karsten</creatorcontrib><title>Reduced Elimination of Cyclosporine A in Elderly (>65 Years) Kidney Transplant Recipients</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>Physiologic functions that may affect pharmacokinetics of drugs are altered in elderly patients. The current study was performed to elucidate the effect of age on cyclosporine A (CsA) pharmacokinetics in renal transplant recipients.
Twenty-five renal transplant recipients on CsA treatment were included in the study. CsA doses were adjusted by C2 monitoring. The patients were divided into two groups based on age; elderly: more than 65 years (n=11, mean 73 years) and younger: 18 to 64 years (n=14, mean 43 years). A full 12-hr pharmacokinetic profile was performed during stable phase. CsA whole blood and intracellular T-lymphocytes concentrations (first 6 hr) were measured. Genotyping of the CYP3A5*1/*3 and ABCB1 (C1236T, G2677T, C3435T) polymorphisms and quantification of whole blood mRNA ABCB1 expression were performed in all patients.
Elderly patients achieved target C2 levels with lower CsA doses than the younger patients (4.3+/-0.8 vs. 6.1+/-2.1 mg/day/kg, P=0.025) because of lower clearance of CsA (22.7+/-5.1 vs. 30.5+/-11.1 L/hr, P=0.031). Elderly patients also showed 44% higher intracellular-to-whole blood CsA ratio than younger patients (P=0.02). Neither the CYP3A5*1, the ABCB1 genotypes nor mRNA ABCB1 expression revealed any significant influence on CsA pharmacokinetics.
The clearance of CsA decreased with increasing age. In addition, elderly patients had a significant larger proportion of the whole blood CsA concentration located at the site of action (within T lymphocytes). This indicates that in elderly recipients it might be safe to aim for an even lower whole blood target levels than current guidelines propose.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aryl Hydrocarbon Hydroxylases - genetics</subject><subject>ATP Binding Cassette Transporter, Sub-Family B</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - genetics</subject><subject>Biological and medical sciences</subject><subject>Cyclosporine - adverse effects</subject><subject>Cyclosporine - blood</subject><subject>Cyclosporine - pharmacokinetics</subject><subject>Cyclosporine - therapeutic use</subject><subject>Cytochrome P-450 CYP2A6</subject><subject>Drug Administration Schedule</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Gene Expression Regulation</subject><subject>Genotype</subject><subject>Humans</subject><subject>Immunosuppressive Agents - adverse effects</subject><subject>Immunosuppressive Agents - blood</subject><subject>Immunosuppressive Agents - pharmacokinetics</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Kidney Transplantation - immunology</subject><subject>Kidney Transplantation - physiology</subject><subject>Medical sciences</subject><subject>Metabolic Clearance Rate</subject><subject>Middle Aged</subject><subject>Pilot Projects</subject><subject>Prospective Studies</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>T-Lymphocytes - immunology</subject><subject>Tissue, organ and graft immunology</subject><subject>Young Adult</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkctKxDAUhoMoOo4-gSDZKLroeNJc2m6EYRgvOOAw1MWsSpqmEOnNpF307Y1MUXB1Fuf7fw7fQeiKwIJAEj2k2wXkQKimJCaxlCwXR2hGOGWBgBiO0QyAkYBQGp2hc-c-AYDTKDpFZyQBygDEDO13uhiULvC6MrVpZG_aBrclXo2qal3XWtNovMSm8UChbTXiu0fB8V5L6-7xmykaPeLUysZ1lWx6vNPKdEY3vbtAJ6WsnL6c5hx9PK3T1UuweX9-XS03gWI86YMyKYsCwpwDF0JxIRlIngDoiEupGClBSb-jIlcxqKgsZEJC4JxFjOacCTpHt4fezrZfg3Z9VhundOXP0e3gshCoEIxzD9IDqGzrnNVl1llTSztmBLIfo1m6zf4b9anrqX7Ia138ZSaFHriZAOmUrErvQhn3y4WQ-C_QkH4D-EZ-OQ</recordid><startdate>20081127</startdate><enddate>20081127</enddate><creator>FALCK, Pal</creator><creator>ASBERG, Anders</creator><creator>BYBERG, Karen-Therese</creator><creator>BREMER, Sara</creator><creator>BERGAN, Stein</creator><creator>REUBSAET, Jan L. 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Psychology</topic><topic>Fundamental immunology</topic><topic>Gene Expression Regulation</topic><topic>Genotype</topic><topic>Humans</topic><topic>Immunosuppressive Agents - adverse effects</topic><topic>Immunosuppressive Agents - blood</topic><topic>Immunosuppressive Agents - pharmacokinetics</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Kidney Transplantation - immunology</topic><topic>Kidney Transplantation - physiology</topic><topic>Medical sciences</topic><topic>Metabolic Clearance Rate</topic><topic>Middle Aged</topic><topic>Pilot Projects</topic><topic>Prospective Studies</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>T-Lymphocytes - immunology</topic><topic>Tissue, organ and graft immunology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>FALCK, Pal</creatorcontrib><creatorcontrib>ASBERG, Anders</creatorcontrib><creatorcontrib>BYBERG, Karen-Therese</creatorcontrib><creatorcontrib>BREMER, Sara</creatorcontrib><creatorcontrib>BERGAN, Stein</creatorcontrib><creatorcontrib>REUBSAET, Jan L. E</creatorcontrib><creatorcontrib>MIDTVEDT, Karsten</creatorcontrib><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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>FALCK, Pal</au><au>ASBERG, Anders</au><au>BYBERG, Karen-Therese</au><au>BREMER, Sara</au><au>BERGAN, Stein</au><au>REUBSAET, Jan L. E</au><au>MIDTVEDT, Karsten</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reduced Elimination of Cyclosporine A in Elderly (>65 Years) Kidney Transplant Recipients</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2008-11-27</date><risdate>2008</risdate><volume>86</volume><issue>10</issue><spage>1379</spage><epage>1383</epage><pages>1379-1383</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><coden>TRPLAU</coden><abstract>Physiologic functions that may affect pharmacokinetics of drugs are altered in elderly patients. The current study was performed to elucidate the effect of age on cyclosporine A (CsA) pharmacokinetics in renal transplant recipients.
Twenty-five renal transplant recipients on CsA treatment were included in the study. CsA doses were adjusted by C2 monitoring. The patients were divided into two groups based on age; elderly: more than 65 years (n=11, mean 73 years) and younger: 18 to 64 years (n=14, mean 43 years). A full 12-hr pharmacokinetic profile was performed during stable phase. CsA whole blood and intracellular T-lymphocytes concentrations (first 6 hr) were measured. Genotyping of the CYP3A5*1/*3 and ABCB1 (C1236T, G2677T, C3435T) polymorphisms and quantification of whole blood mRNA ABCB1 expression were performed in all patients.
Elderly patients achieved target C2 levels with lower CsA doses than the younger patients (4.3+/-0.8 vs. 6.1+/-2.1 mg/day/kg, P=0.025) because of lower clearance of CsA (22.7+/-5.1 vs. 30.5+/-11.1 L/hr, P=0.031). Elderly patients also showed 44% higher intracellular-to-whole blood CsA ratio than younger patients (P=0.02). Neither the CYP3A5*1, the ABCB1 genotypes nor mRNA ABCB1 expression revealed any significant influence on CsA pharmacokinetics.
The clearance of CsA decreased with increasing age. In addition, elderly patients had a significant larger proportion of the whole blood CsA concentration located at the site of action (within T lymphocytes). This indicates that in elderly recipients it might be safe to aim for an even lower whole blood target levels than current guidelines propose.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>19034006</pmid><doi>10.1097/TP.0b013e31818aa4b6</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Aryl Hydrocarbon Hydroxylases - genetics ATP Binding Cassette Transporter, Sub-Family B ATP-Binding Cassette, Sub-Family B, Member 1 - genetics Biological and medical sciences Cyclosporine - adverse effects Cyclosporine - blood Cyclosporine - pharmacokinetics Cyclosporine - therapeutic use Cytochrome P-450 CYP2A6 Drug Administration Schedule Fundamental and applied biological sciences. Psychology Fundamental immunology Gene Expression Regulation Genotype Humans Immunosuppressive Agents - adverse effects Immunosuppressive Agents - blood Immunosuppressive Agents - pharmacokinetics Immunosuppressive Agents - therapeutic use Kidney Transplantation - immunology Kidney Transplantation - physiology Medical sciences Metabolic Clearance Rate Middle Aged Pilot Projects Prospective Studies Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases T-Lymphocytes - immunology Tissue, organ and graft immunology Young Adult |
| title | Reduced Elimination of Cyclosporine A in Elderly (>65 Years) Kidney Transplant Recipients |
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