A Simple Novel Technique to Estimate Tacrolimus Dosages During the Early Post Kidney Transplantation Period
Abstract Background Tacrolimus pharmacokinetics prediction by CYP3A5 genotyping is not available in many Asian resource-limited settings. Therefore, an alternative technique is needed to estimate the dose of tacrolimus perioperatively. The 12-hour level after the first dose (C12-0) is an alternative...
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| Veröffentlicht in: | Transplantation proceedings 2015-10, Vol.47 (8), p.2433-2438 |
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| creator | Townamchai, N Chancharoenthana, W Vadcharavivad, S Chariyavilaskul, P Pongpirul, K Leelahavanichkul, A Watanatorn, S Avihingsanon, Y Praditpornsilpa, K Srisawat, N |
| description | Abstract Background Tacrolimus pharmacokinetics prediction by CYP3A5 genotyping is not available in many Asian resource-limited settings. Therefore, an alternative technique is needed to estimate the dose of tacrolimus perioperatively. The 12-hour level after the first dose (C12-0) is an alternative technique for estimating the dose of tacrolimus. This simple and inexpensive calculation technique can be used by any transplantation center. Methods A prospective study on a cohort of 57 incident post-kidney transplant recipients was conducted. The whole-blood tacrolimus trough level (C12-0) was measured at 12 hours after the first dose (0.1 mg/kg) of orally administered tacrolimus during transplantation. Concomitant medications with CYP3A5 inhibitors/inducers were not allowed. Genotyping for CYP3A5 expression was carried out by reverse transcription polymerase chain reaction. The dosages and trough levels of tacrolimus at postoperative day 7 and postoperative months 1 to 3 were measured and analyzed for the dose requirements for therapeutic levels (mg/kg/d). Results The doses of tacrolimus were widely diverse, ranging from 0.049 to 0.260 mg/kg/d and 0.031 to 0.298 mg/kg/d at day 7 and months 1 to 3, respectively. There were 9, 28, and 20 patients (15.8%, 49.1%, and 35.1%) with CYP3A5 *1/*1 , *1/*3 , and *3/*3 , respectively. The CYP3A5 genotypes were significantly correlated with the target tacrolimus dose at day 7 (r2 = 0.307) and the stable dose at months 1 to 3 (r2 = 0.337). The C12-0 level also was significantly correlated with the dose of tacrolimus at day 7 (r2 = 0.546) and the stable dose at months 1 to 3 (r2 = 0.406). Conclusions There were strong correlations between the C12-0 level and the tacrolimus doses during the perioperative period at day 7 and the stable period at 1 to 3 months. Countries with limited resources for genotype testing can use the C12-0 level as an alternative to estimate the tacrolimus dose. |
| doi_str_mv | 10.1016/j.transproceed.2015.08.013 |
| format | Article |
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Therefore, an alternative technique is needed to estimate the dose of tacrolimus perioperatively. The 12-hour level after the first dose (C12-0) is an alternative technique for estimating the dose of tacrolimus. This simple and inexpensive calculation technique can be used by any transplantation center. Methods A prospective study on a cohort of 57 incident post-kidney transplant recipients was conducted. The whole-blood tacrolimus trough level (C12-0) was measured at 12 hours after the first dose (0.1 mg/kg) of orally administered tacrolimus during transplantation. Concomitant medications with CYP3A5 inhibitors/inducers were not allowed. Genotyping for CYP3A5 expression was carried out by reverse transcription polymerase chain reaction. The dosages and trough levels of tacrolimus at postoperative day 7 and postoperative months 1 to 3 were measured and analyzed for the dose requirements for therapeutic levels (mg/kg/d). Results The doses of tacrolimus were widely diverse, ranging from 0.049 to 0.260 mg/kg/d and 0.031 to 0.298 mg/kg/d at day 7 and months 1 to 3, respectively. There were 9, 28, and 20 patients (15.8%, 49.1%, and 35.1%) with CYP3A5 *1/*1 , *1/*3 , and *3/*3 , respectively. The CYP3A5 genotypes were significantly correlated with the target tacrolimus dose at day 7 (r2 = 0.307) and the stable dose at months 1 to 3 (r2 = 0.337). The C12-0 level also was significantly correlated with the dose of tacrolimus at day 7 (r2 = 0.546) and the stable dose at months 1 to 3 (r2 = 0.406). Conclusions There were strong correlations between the C12-0 level and the tacrolimus doses during the perioperative period at day 7 and the stable period at 1 to 3 months. Countries with limited resources for genotype testing can use the C12-0 level as an alternative to estimate the tacrolimus dose.</description><identifier>ISSN: 0041-1345</identifier><identifier>EISSN: 1873-2623</identifier><identifier>DOI: 10.1016/j.transproceed.2015.08.013</identifier><identifier>PMID: 26518946</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Asian Continental Ancestry Group - genetics ; Cytochrome P-450 CYP3A - genetics ; Dose-Response Relationship, Drug ; Female ; Genotype ; Humans ; Immunosuppressive Agents - administration & dosage ; Immunosuppressive Agents - pharmacokinetics ; Kidney Failure, Chronic - genetics ; Kidney Failure, Chronic - metabolism ; Kidney Failure, Chronic - surgery ; Kidney Transplantation ; Male ; Middle Aged ; Prospective Studies ; Surgery ; Tacrolimus - administration & dosage ; Tacrolimus - pharmacokinetics</subject><ispartof>Transplantation proceedings, 2015-10, Vol.47 (8), p.2433-2438</ispartof><rights>Elsevier Inc.</rights><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-7e1ef7b174e863d78ac71f81dc258805ba19917ab6d32f879301c8ad550b1b283</citedby><cites>FETCH-LOGICAL-c435t-7e1ef7b174e863d78ac71f81dc258805ba19917ab6d32f879301c8ad550b1b283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0041134515007599$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26518946$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Townamchai, N</creatorcontrib><creatorcontrib>Chancharoenthana, W</creatorcontrib><creatorcontrib>Vadcharavivad, S</creatorcontrib><creatorcontrib>Chariyavilaskul, P</creatorcontrib><creatorcontrib>Pongpirul, K</creatorcontrib><creatorcontrib>Leelahavanichkul, A</creatorcontrib><creatorcontrib>Watanatorn, S</creatorcontrib><creatorcontrib>Avihingsanon, Y</creatorcontrib><creatorcontrib>Praditpornsilpa, K</creatorcontrib><creatorcontrib>Srisawat, N</creatorcontrib><title>A Simple Novel Technique to Estimate Tacrolimus Dosages During the Early Post Kidney Transplantation Period</title><title>Transplantation proceedings</title><addtitle>Transplant Proc</addtitle><description>Abstract Background Tacrolimus pharmacokinetics prediction by CYP3A5 genotyping is not available in many Asian resource-limited settings. Therefore, an alternative technique is needed to estimate the dose of tacrolimus perioperatively. The 12-hour level after the first dose (C12-0) is an alternative technique for estimating the dose of tacrolimus. This simple and inexpensive calculation technique can be used by any transplantation center. Methods A prospective study on a cohort of 57 incident post-kidney transplant recipients was conducted. The whole-blood tacrolimus trough level (C12-0) was measured at 12 hours after the first dose (0.1 mg/kg) of orally administered tacrolimus during transplantation. Concomitant medications with CYP3A5 inhibitors/inducers were not allowed. Genotyping for CYP3A5 expression was carried out by reverse transcription polymerase chain reaction. The dosages and trough levels of tacrolimus at postoperative day 7 and postoperative months 1 to 3 were measured and analyzed for the dose requirements for therapeutic levels (mg/kg/d). Results The doses of tacrolimus were widely diverse, ranging from 0.049 to 0.260 mg/kg/d and 0.031 to 0.298 mg/kg/d at day 7 and months 1 to 3, respectively. There were 9, 28, and 20 patients (15.8%, 49.1%, and 35.1%) with CYP3A5 *1/*1 , *1/*3 , and *3/*3 , respectively. The CYP3A5 genotypes were significantly correlated with the target tacrolimus dose at day 7 (r2 = 0.307) and the stable dose at months 1 to 3 (r2 = 0.337). The C12-0 level also was significantly correlated with the dose of tacrolimus at day 7 (r2 = 0.546) and the stable dose at months 1 to 3 (r2 = 0.406). Conclusions There were strong correlations between the C12-0 level and the tacrolimus doses during the perioperative period at day 7 and the stable period at 1 to 3 months. Countries with limited resources for genotype testing can use the C12-0 level as an alternative to estimate the tacrolimus dose.</description><subject>Adult</subject><subject>Asian Continental Ancestry Group - genetics</subject><subject>Cytochrome P-450 CYP3A - genetics</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Genotype</subject><subject>Humans</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Immunosuppressive Agents - pharmacokinetics</subject><subject>Kidney Failure, Chronic - genetics</subject><subject>Kidney Failure, Chronic - metabolism</subject><subject>Kidney Failure, Chronic - surgery</subject><subject>Kidney Transplantation</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Prospective Studies</subject><subject>Surgery</subject><subject>Tacrolimus - administration & dosage</subject><subject>Tacrolimus - pharmacokinetics</subject><issn>0041-1345</issn><issn>1873-2623</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhi0EosvCX0AWJy5JPXYSOxyQqnahiAoqdTlbjjNpvc3GW9uptP8eL9tKiBO-jKx55-N9hpAPwEpg0JxuyhTMFHfBW8S-5AzqkqmSgXhBFqCkKHjDxUuyYKyCAkRVn5A3MW5Y_vNKvCYnvKlBtVWzIPdn9MZtdyPSH_4RR7pGeze5hxlp8nQVk9uahHRtbPCj286RXvhobjHHObjplqY7pCsTxj299jHR766fcE_Xf_YbzZRMcn6i1xic79-SV4MZI757ikvy68tqfX5ZXP38-u387KqwlahTIRFwkB3IClUjeqmMlTAo6C2vlWJ1Z6BtQZqu6QUflGwFA6tMX9esg44rsSQfj30zoewkJr110eKY90E_Rw2Sq0Yykd-SfDpKs78YAw56F7LlsNfA9AG23ui_YesDbM2UzrBz8funOXO3zbnn0me6WXBxFGB2--gw6GgdThZ7F9Am3Xv3f3M-_9PGjm5y1oz3uMe48XOYMk8NOnLN9M3h7IerQ82YrNtW_Ab7L6zI</recordid><startdate>20151001</startdate><enddate>20151001</enddate><creator>Townamchai, N</creator><creator>Chancharoenthana, W</creator><creator>Vadcharavivad, S</creator><creator>Chariyavilaskul, P</creator><creator>Pongpirul, K</creator><creator>Leelahavanichkul, A</creator><creator>Watanatorn, S</creator><creator>Avihingsanon, Y</creator><creator>Praditpornsilpa, K</creator><creator>Srisawat, N</creator><general>Elsevier 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>7X8</scope></search><sort><creationdate>20151001</creationdate><title>A Simple Novel Technique to Estimate Tacrolimus Dosages During the Early Post Kidney Transplantation Period</title><author>Townamchai, N ; Chancharoenthana, W ; Vadcharavivad, S ; Chariyavilaskul, P ; Pongpirul, K ; Leelahavanichkul, A ; Watanatorn, S ; Avihingsanon, Y ; Praditpornsilpa, K ; Srisawat, N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-7e1ef7b174e863d78ac71f81dc258805ba19917ab6d32f879301c8ad550b1b283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Asian Continental Ancestry Group - genetics</topic><topic>Cytochrome P-450 CYP3A - genetics</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Genotype</topic><topic>Humans</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Immunosuppressive Agents - pharmacokinetics</topic><topic>Kidney Failure, Chronic - genetics</topic><topic>Kidney Failure, Chronic - metabolism</topic><topic>Kidney Failure, Chronic - surgery</topic><topic>Kidney Transplantation</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Prospective Studies</topic><topic>Surgery</topic><topic>Tacrolimus - administration & dosage</topic><topic>Tacrolimus - pharmacokinetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Townamchai, N</creatorcontrib><creatorcontrib>Chancharoenthana, W</creatorcontrib><creatorcontrib>Vadcharavivad, S</creatorcontrib><creatorcontrib>Chariyavilaskul, P</creatorcontrib><creatorcontrib>Pongpirul, K</creatorcontrib><creatorcontrib>Leelahavanichkul, A</creatorcontrib><creatorcontrib>Watanatorn, S</creatorcontrib><creatorcontrib>Avihingsanon, Y</creatorcontrib><creatorcontrib>Praditpornsilpa, K</creatorcontrib><creatorcontrib>Srisawat, N</creatorcontrib><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>Transplantation proceedings</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Townamchai, N</au><au>Chancharoenthana, W</au><au>Vadcharavivad, S</au><au>Chariyavilaskul, P</au><au>Pongpirul, K</au><au>Leelahavanichkul, A</au><au>Watanatorn, S</au><au>Avihingsanon, Y</au><au>Praditpornsilpa, K</au><au>Srisawat, N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Simple Novel Technique to Estimate Tacrolimus Dosages During the Early Post Kidney Transplantation Period</atitle><jtitle>Transplantation proceedings</jtitle><addtitle>Transplant Proc</addtitle><date>2015-10-01</date><risdate>2015</risdate><volume>47</volume><issue>8</issue><spage>2433</spage><epage>2438</epage><pages>2433-2438</pages><issn>0041-1345</issn><eissn>1873-2623</eissn><abstract>Abstract Background Tacrolimus pharmacokinetics prediction by CYP3A5 genotyping is not available in many Asian resource-limited settings. Therefore, an alternative technique is needed to estimate the dose of tacrolimus perioperatively. The 12-hour level after the first dose (C12-0) is an alternative technique for estimating the dose of tacrolimus. This simple and inexpensive calculation technique can be used by any transplantation center. Methods A prospective study on a cohort of 57 incident post-kidney transplant recipients was conducted. The whole-blood tacrolimus trough level (C12-0) was measured at 12 hours after the first dose (0.1 mg/kg) of orally administered tacrolimus during transplantation. Concomitant medications with CYP3A5 inhibitors/inducers were not allowed. Genotyping for CYP3A5 expression was carried out by reverse transcription polymerase chain reaction. The dosages and trough levels of tacrolimus at postoperative day 7 and postoperative months 1 to 3 were measured and analyzed for the dose requirements for therapeutic levels (mg/kg/d). Results The doses of tacrolimus were widely diverse, ranging from 0.049 to 0.260 mg/kg/d and 0.031 to 0.298 mg/kg/d at day 7 and months 1 to 3, respectively. There were 9, 28, and 20 patients (15.8%, 49.1%, and 35.1%) with CYP3A5 *1/*1 , *1/*3 , and *3/*3 , respectively. The CYP3A5 genotypes were significantly correlated with the target tacrolimus dose at day 7 (r2 = 0.307) and the stable dose at months 1 to 3 (r2 = 0.337). The C12-0 level also was significantly correlated with the dose of tacrolimus at day 7 (r2 = 0.546) and the stable dose at months 1 to 3 (r2 = 0.406). Conclusions There were strong correlations between the C12-0 level and the tacrolimus doses during the perioperative period at day 7 and the stable period at 1 to 3 months. Countries with limited resources for genotype testing can use the C12-0 level as an alternative to estimate the tacrolimus dose.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26518946</pmid><doi>10.1016/j.transproceed.2015.08.013</doi><tpages>6</tpages></addata></record> |
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| subjects | Adult Asian Continental Ancestry Group - genetics Cytochrome P-450 CYP3A - genetics Dose-Response Relationship, Drug Female Genotype Humans Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - pharmacokinetics Kidney Failure, Chronic - genetics Kidney Failure, Chronic - metabolism Kidney Failure, Chronic - surgery Kidney Transplantation Male Middle Aged Prospective Studies Surgery Tacrolimus - administration & dosage Tacrolimus - pharmacokinetics |
| title | A Simple Novel Technique to Estimate Tacrolimus Dosages During the Early Post Kidney Transplantation Period |
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