Tacrolimus blood concentration increase depends on administration route when combined with voriconazole in pediatric stem cell transplant recipients
Background Understanding of TAC pharmacokinetics is required to avoid both overdosing and underdosing. VRCZ is known to increase the TAC blood concentration by inhibiting CYP3A4; however, detailed, practical information on pediatric cases is still scarce. Herein, we investigated the association betw...
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| Veröffentlicht in: | Pediatric transplantation 2020-02, Vol.24 (1), p.e13619-n/a |
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| container_title | Pediatric transplantation |
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| creator | Utano, Tomoyuki Kato, Motohiro Osumi, Tomoo Shioda, Yoko Kiyotani, Chikako Terashima, Keita Tomizawa, Daisuke Matsumoto, Kimikazu Yamatani, Akimasa |
| description | Background
Understanding of TAC pharmacokinetics is required to avoid both overdosing and underdosing. VRCZ is known to increase the TAC blood concentration by inhibiting CYP3A4; however, detailed, practical information on pediatric cases is still scarce. Herein, we investigated the association between the TAC blood concentration and dosage focusing on the administration route and concomitant use of VRCZ in children.
Methods
In total, 38 children who received TAC during stem cell transplantation at our hospital between January 2013 and April 2018 were included. The ratio of the TAC blood concentration (ng/mL) to dosage (mg/kg/day) (C/D) was calculated at the last continuous intravenous infusion (C/Div) and after switching to oral administration (C/Dpo).
Results
Patients with VRCZ (n = 14) showed a higher C/D regardless of administration route (median C/Div: with VRCZ/without VRCZ = 832/643, median C/Dpo: with VRCZ/without VRCZ = 339/45). Additionally, the (C/Div)/(C/Dpo) was about one‐fourth in cases with VRCZ; the median (C/Div)/(C/Dpo) was 3.3 for cases with VRCZ and 13.5 for cases without VRCZ. Interestingly, the increase in the TAC blood concentration due to VRCZ was higher when TAC was administered orally, especially in adolescent patients.
Conclusions
To obtain an optimal TAC blood concentration, dose adjustment based on multiple factors, such as administration route, concomitant use of VRCZ, and age, is required. |
| doi_str_mv | 10.1111/petr.13619 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2344056998</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2344056998</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3579-b38987ecc6153f4d9aa72c096a7241a5742c9690e8167ef54d54a130dfd369373</originalsourceid><addsrcrecordid>eNp9kU1LxDAQhoMofqxe_AES8CZUkyZNm6OIXyAosp5LNplipE1qkrro7_AHm3XVo7lMGJ55BuZF6JCSU5rf2QgpnFImqNxAu5RJWTDCxeb3vy4Y5eUO2ovxhRAqeMO30Q6jTUkqVu2iz7nSwfd2mCJe9N4brL3T4FJQyXqHrdMBVARsYARnIs49ZQbrbPxFgp8S4OUzuDw7LKwDg5c2PeM3H2y2qQ_fQxbhEYxVKfdwTDBgDX2Ps8TFsVcu4QDajjavjvtoq1N9hIOfOkNPV5fzi5vi7v769uL8rtCsqmWxYI1satBa0Ip13Eil6lITKXLhVFU1L7UUkkBDRQ1dxU3FFWXEdIYJyWo2Q8dr7xj86wQxtS9-Ci6vbEvGOamElE2mTtZUPlSMAbp2DHZQ4b2lpF0F0K4CaL8DyPDRj3JaDGD-0N-LZ4CugaXt4f0fVftwOX9cS78AGOqUaA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2344056998</pqid></control><display><type>article</type><title>Tacrolimus blood concentration increase depends on administration route when combined with voriconazole in pediatric stem cell transplant recipients</title><source>MEDLINE</source><source>Wiley Journals</source><creator>Utano, Tomoyuki ; Kato, Motohiro ; Osumi, Tomoo ; Shioda, Yoko ; Kiyotani, Chikako ; Terashima, Keita ; Tomizawa, Daisuke ; Matsumoto, Kimikazu ; Yamatani, Akimasa</creator><creatorcontrib>Utano, Tomoyuki ; Kato, Motohiro ; Osumi, Tomoo ; Shioda, Yoko ; Kiyotani, Chikako ; Terashima, Keita ; Tomizawa, Daisuke ; Matsumoto, Kimikazu ; Yamatani, Akimasa</creatorcontrib><description>Background
Understanding of TAC pharmacokinetics is required to avoid both overdosing and underdosing. VRCZ is known to increase the TAC blood concentration by inhibiting CYP3A4; however, detailed, practical information on pediatric cases is still scarce. Herein, we investigated the association between the TAC blood concentration and dosage focusing on the administration route and concomitant use of VRCZ in children.
Methods
In total, 38 children who received TAC during stem cell transplantation at our hospital between January 2013 and April 2018 were included. The ratio of the TAC blood concentration (ng/mL) to dosage (mg/kg/day) (C/D) was calculated at the last continuous intravenous infusion (C/Div) and after switching to oral administration (C/Dpo).
Results
Patients with VRCZ (n = 14) showed a higher C/D regardless of administration route (median C/Div: with VRCZ/without VRCZ = 832/643, median C/Dpo: with VRCZ/without VRCZ = 339/45). Additionally, the (C/Div)/(C/Dpo) was about one‐fourth in cases with VRCZ; the median (C/Div)/(C/Dpo) was 3.3 for cases with VRCZ and 13.5 for cases without VRCZ. Interestingly, the increase in the TAC blood concentration due to VRCZ was higher when TAC was administered orally, especially in adolescent patients.
Conclusions
To obtain an optimal TAC blood concentration, dose adjustment based on multiple factors, such as administration route, concomitant use of VRCZ, and age, is required.</description><identifier>ISSN: 1397-3142</identifier><identifier>EISSN: 1399-3046</identifier><identifier>DOI: 10.1111/petr.13619</identifier><identifier>PMID: 31820535</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>Administration, Oral ; Adolescent ; Antifungal agents ; Blood levels ; Child ; Child, Preschool ; Children ; Dosage ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; drug interaction ; Drug Therapy, Combination ; Female ; Graft Rejection - prevention & control ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunosuppressive Agents - administration & dosage ; Immunosuppressive Agents - blood ; Immunosuppressive Agents - pharmacokinetics ; Immunosuppressive Agents - therapeutic use ; Infant ; Infusions, Intravenous ; Intravenous administration ; Linear Models ; Male ; Oral administration ; Patients ; Pediatrics ; Pharmacokinetics ; Retrospective Studies ; Stem cell transplantation ; Stem cells ; Tacrolimus ; Tacrolimus - administration & dosage ; Tacrolimus - blood ; Tacrolimus - pharmacokinetics ; Tacrolimus - therapeutic use ; Transplants & implants ; Voriconazole ; Voriconazole - administration & dosage ; Voriconazole - blood ; Voriconazole - pharmacokinetics ; Voriconazole - therapeutic use</subject><ispartof>Pediatric transplantation, 2020-02, Vol.24 (1), p.e13619-n/a</ispartof><rights>2019 Wiley Periodicals, Inc.</rights><rights>2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3579-b38987ecc6153f4d9aa72c096a7241a5742c9690e8167ef54d54a130dfd369373</citedby><cites>FETCH-LOGICAL-c3579-b38987ecc6153f4d9aa72c096a7241a5742c9690e8167ef54d54a130dfd369373</cites><orcidid>0000-0003-1520-7007 ; 0000-0003-1373-9122</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fpetr.13619$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fpetr.13619$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31820535$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Utano, Tomoyuki</creatorcontrib><creatorcontrib>Kato, Motohiro</creatorcontrib><creatorcontrib>Osumi, Tomoo</creatorcontrib><creatorcontrib>Shioda, Yoko</creatorcontrib><creatorcontrib>Kiyotani, Chikako</creatorcontrib><creatorcontrib>Terashima, Keita</creatorcontrib><creatorcontrib>Tomizawa, Daisuke</creatorcontrib><creatorcontrib>Matsumoto, Kimikazu</creatorcontrib><creatorcontrib>Yamatani, Akimasa</creatorcontrib><title>Tacrolimus blood concentration increase depends on administration route when combined with voriconazole in pediatric stem cell transplant recipients</title><title>Pediatric transplantation</title><addtitle>Pediatr Transplant</addtitle><description>Background
Understanding of TAC pharmacokinetics is required to avoid both overdosing and underdosing. VRCZ is known to increase the TAC blood concentration by inhibiting CYP3A4; however, detailed, practical information on pediatric cases is still scarce. Herein, we investigated the association between the TAC blood concentration and dosage focusing on the administration route and concomitant use of VRCZ in children.
Methods
In total, 38 children who received TAC during stem cell transplantation at our hospital between January 2013 and April 2018 were included. The ratio of the TAC blood concentration (ng/mL) to dosage (mg/kg/day) (C/D) was calculated at the last continuous intravenous infusion (C/Div) and after switching to oral administration (C/Dpo).
Results
Patients with VRCZ (n = 14) showed a higher C/D regardless of administration route (median C/Div: with VRCZ/without VRCZ = 832/643, median C/Dpo: with VRCZ/without VRCZ = 339/45). Additionally, the (C/Div)/(C/Dpo) was about one‐fourth in cases with VRCZ; the median (C/Div)/(C/Dpo) was 3.3 for cases with VRCZ and 13.5 for cases without VRCZ. Interestingly, the increase in the TAC blood concentration due to VRCZ was higher when TAC was administered orally, especially in adolescent patients.
Conclusions
To obtain an optimal TAC blood concentration, dose adjustment based on multiple factors, such as administration route, concomitant use of VRCZ, and age, is required.</description><subject>Administration, Oral</subject><subject>Adolescent</subject><subject>Antifungal agents</subject><subject>Blood levels</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Dosage</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Administration Schedule</subject><subject>drug interaction</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>Graft Rejection - prevention & control</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Humans</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Immunosuppressive Agents - blood</subject><subject>Immunosuppressive Agents - pharmacokinetics</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Infant</subject><subject>Infusions, Intravenous</subject><subject>Intravenous administration</subject><subject>Linear Models</subject><subject>Male</subject><subject>Oral administration</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Pharmacokinetics</subject><subject>Retrospective Studies</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Tacrolimus</subject><subject>Tacrolimus - administration & dosage</subject><subject>Tacrolimus - blood</subject><subject>Tacrolimus - pharmacokinetics</subject><subject>Tacrolimus - therapeutic use</subject><subject>Transplants & implants</subject><subject>Voriconazole</subject><subject>Voriconazole - administration & dosage</subject><subject>Voriconazole - blood</subject><subject>Voriconazole - pharmacokinetics</subject><subject>Voriconazole - therapeutic use</subject><issn>1397-3142</issn><issn>1399-3046</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1LxDAQhoMofqxe_AES8CZUkyZNm6OIXyAosp5LNplipE1qkrro7_AHm3XVo7lMGJ55BuZF6JCSU5rf2QgpnFImqNxAu5RJWTDCxeb3vy4Y5eUO2ovxhRAqeMO30Q6jTUkqVu2iz7nSwfd2mCJe9N4brL3T4FJQyXqHrdMBVARsYARnIs49ZQbrbPxFgp8S4OUzuDw7LKwDg5c2PeM3H2y2qQ_fQxbhEYxVKfdwTDBgDX2Ps8TFsVcu4QDajjavjvtoq1N9hIOfOkNPV5fzi5vi7v769uL8rtCsqmWxYI1satBa0Ip13Eil6lITKXLhVFU1L7UUkkBDRQ1dxU3FFWXEdIYJyWo2Q8dr7xj86wQxtS9-Ci6vbEvGOamElE2mTtZUPlSMAbp2DHZQ4b2lpF0F0K4CaL8DyPDRj3JaDGD-0N-LZ4CugaXt4f0fVftwOX9cS78AGOqUaA</recordid><startdate>202002</startdate><enddate>202002</enddate><creator>Utano, Tomoyuki</creator><creator>Kato, Motohiro</creator><creator>Osumi, Tomoo</creator><creator>Shioda, Yoko</creator><creator>Kiyotani, Chikako</creator><creator>Terashima, Keita</creator><creator>Tomizawa, Daisuke</creator><creator>Matsumoto, Kimikazu</creator><creator>Yamatani, Akimasa</creator><general>Wiley Subscription Services, 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><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><orcidid>https://orcid.org/0000-0003-1520-7007</orcidid><orcidid>https://orcid.org/0000-0003-1373-9122</orcidid></search><sort><creationdate>202002</creationdate><title>Tacrolimus blood concentration increase depends on administration route when combined with voriconazole in pediatric stem cell transplant recipients</title><author>Utano, Tomoyuki ; Kato, Motohiro ; Osumi, Tomoo ; Shioda, Yoko ; Kiyotani, Chikako ; Terashima, Keita ; Tomizawa, Daisuke ; Matsumoto, Kimikazu ; Yamatani, Akimasa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3579-b38987ecc6153f4d9aa72c096a7241a5742c9690e8167ef54d54a130dfd369373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Administration, Oral</topic><topic>Adolescent</topic><topic>Antifungal agents</topic><topic>Blood levels</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Children</topic><topic>Dosage</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Administration Schedule</topic><topic>drug interaction</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>Graft Rejection - prevention & control</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Humans</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Immunosuppressive Agents - blood</topic><topic>Immunosuppressive Agents - pharmacokinetics</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Infant</topic><topic>Infusions, Intravenous</topic><topic>Intravenous administration</topic><topic>Linear Models</topic><topic>Male</topic><topic>Oral administration</topic><topic>Patients</topic><topic>Pediatrics</topic><topic>Pharmacokinetics</topic><topic>Retrospective Studies</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Tacrolimus</topic><topic>Tacrolimus - administration & dosage</topic><topic>Tacrolimus - blood</topic><topic>Tacrolimus - pharmacokinetics</topic><topic>Tacrolimus - therapeutic use</topic><topic>Transplants & implants</topic><topic>Voriconazole</topic><topic>Voriconazole - administration & dosage</topic><topic>Voriconazole - blood</topic><topic>Voriconazole - pharmacokinetics</topic><topic>Voriconazole - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Utano, Tomoyuki</creatorcontrib><creatorcontrib>Kato, Motohiro</creatorcontrib><creatorcontrib>Osumi, Tomoo</creatorcontrib><creatorcontrib>Shioda, Yoko</creatorcontrib><creatorcontrib>Kiyotani, Chikako</creatorcontrib><creatorcontrib>Terashima, Keita</creatorcontrib><creatorcontrib>Tomizawa, Daisuke</creatorcontrib><creatorcontrib>Matsumoto, Kimikazu</creatorcontrib><creatorcontrib>Yamatani, Akimasa</creatorcontrib><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><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Pediatric transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Utano, Tomoyuki</au><au>Kato, Motohiro</au><au>Osumi, Tomoo</au><au>Shioda, Yoko</au><au>Kiyotani, Chikako</au><au>Terashima, Keita</au><au>Tomizawa, Daisuke</au><au>Matsumoto, Kimikazu</au><au>Yamatani, Akimasa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tacrolimus blood concentration increase depends on administration route when combined with voriconazole in pediatric stem cell transplant recipients</atitle><jtitle>Pediatric transplantation</jtitle><addtitle>Pediatr Transplant</addtitle><date>2020-02</date><risdate>2020</risdate><volume>24</volume><issue>1</issue><spage>e13619</spage><epage>n/a</epage><pages>e13619-n/a</pages><issn>1397-3142</issn><eissn>1399-3046</eissn><abstract>Background
Understanding of TAC pharmacokinetics is required to avoid both overdosing and underdosing. VRCZ is known to increase the TAC blood concentration by inhibiting CYP3A4; however, detailed, practical information on pediatric cases is still scarce. Herein, we investigated the association between the TAC blood concentration and dosage focusing on the administration route and concomitant use of VRCZ in children.
Methods
In total, 38 children who received TAC during stem cell transplantation at our hospital between January 2013 and April 2018 were included. The ratio of the TAC blood concentration (ng/mL) to dosage (mg/kg/day) (C/D) was calculated at the last continuous intravenous infusion (C/Div) and after switching to oral administration (C/Dpo).
Results
Patients with VRCZ (n = 14) showed a higher C/D regardless of administration route (median C/Div: with VRCZ/without VRCZ = 832/643, median C/Dpo: with VRCZ/without VRCZ = 339/45). Additionally, the (C/Div)/(C/Dpo) was about one‐fourth in cases with VRCZ; the median (C/Div)/(C/Dpo) was 3.3 for cases with VRCZ and 13.5 for cases without VRCZ. Interestingly, the increase in the TAC blood concentration due to VRCZ was higher when TAC was administered orally, especially in adolescent patients.
Conclusions
To obtain an optimal TAC blood concentration, dose adjustment based on multiple factors, such as administration route, concomitant use of VRCZ, and age, is required.</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31820535</pmid><doi>10.1111/petr.13619</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0003-1520-7007</orcidid><orcidid>https://orcid.org/0000-0003-1373-9122</orcidid></addata></record> |
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| subjects | Administration, Oral Adolescent Antifungal agents Blood levels Child Child, Preschool Children Dosage Dose-Response Relationship, Drug Drug Administration Schedule drug interaction Drug Therapy, Combination Female Graft Rejection - prevention & control Hematopoietic Stem Cell Transplantation Humans Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - blood Immunosuppressive Agents - pharmacokinetics Immunosuppressive Agents - therapeutic use Infant Infusions, Intravenous Intravenous administration Linear Models Male Oral administration Patients Pediatrics Pharmacokinetics Retrospective Studies Stem cell transplantation Stem cells Tacrolimus Tacrolimus - administration & dosage Tacrolimus - blood Tacrolimus - pharmacokinetics Tacrolimus - therapeutic use Transplants & implants Voriconazole Voriconazole - administration & dosage Voriconazole - blood Voriconazole - pharmacokinetics Voriconazole - therapeutic use |
| title | Tacrolimus blood concentration increase depends on administration route when combined with voriconazole in pediatric stem cell transplant recipients |
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