Temporal changes in physiology and haematology in response to high‐ and micro‐doses of recombinant human erythropoietin
There is evidence to suggest athletes have adopted recombinant human erythropoietin (rHuEPO) dosing regimens that diminish the likelihood of being caught by direct detection techniques. However, the temporal response in physiology, performance, and Athlete Biological Passport (ABP) parameters to suc...
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description | There is evidence to suggest athletes have adopted recombinant human erythropoietin (rHuEPO) dosing regimens that diminish the likelihood of being caught by direct detection techniques. However, the temporal response in physiology, performance, and Athlete Biological Passport (ABP) parameters to such regimens is not clearly understood. Participants were assigned to a high‐dose only group (HIGH, n = 8, six rHuEPO doses of 250 IU/kg over two weeks), a combined high micro‐dose group (COMB, n = 8, high‐dose plus nine rHuEPO micro‐doses over a further three weeks), or one of two placebo control groups who received saline in the same pattern as the HIGH (HIGH‐PLACEBO, n = 4) or COMB (COMB‐PLACEBO, n = 4) groups. Temporal changes in physiology and performance were tracked by graded exercise test (GXT) and haemoglobin mass assessment at baseline, after high dose, after micro‐dose (COMB and COMB‐PLACEBO only) and after a four‐week washout. Venous blood samples were collected throughout the baseline, rHuEPO administration, and washout periods to determine the haematological and ABP response to each dosing regimen. Physiological adaptations induced by a two‐week rHuEPO high‐dose were maintained by rHuEPO micro‐dosing for at least three weeks. However, all participants administered rHuEPO registered at least one suspicious ABP value during the administration or washout periods. These results indicate there is sufficient sensitivity in the ABP to detect use of high rHuEPO doping regimens in athletic populations and they provide important empirical examples for use by anti‐doping experts. Copyright © 2017 John Wiley & Sons, Ltd.
The temporal response in physiology, performance and athlete biological passport (ABP) parameters to high or high‐micro recombinant human erythropoietin dosing regimens was assessed in recreational athletes. The physiological adaptations and modest performance improvements induced by a two week rHuEPO high dose were maintained by rHuEPO micro‐dosing for at least three weeks. However, rHuEPO micro‐dosing did not mask previous rHuEPO high‐dosing and all participants administered rHuEPO registered at least one suspicious ABP value during the administration or washout periods. |
doi_str_mv | 10.1002/dta.2176 |
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The temporal response in physiology, performance and athlete biological passport (ABP) parameters to high or high‐micro recombinant human erythropoietin dosing regimens was assessed in recreational athletes. The physiological adaptations and modest performance improvements induced by a two week rHuEPO high dose were maintained by rHuEPO micro‐dosing for at least three weeks. However, rHuEPO micro‐dosing did not mask previous rHuEPO high‐dosing and all participants administered rHuEPO registered at least one suspicious ABP value during the administration or washout periods.</description><identifier>ISSN: 1942-7603</identifier><identifier>EISSN: 1942-7611</identifier><identifier>DOI: 10.1002/dta.2176</identifier><identifier>PMID: 28214385</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>ABP ; Adult ; Blood Volume - drug effects ; doping ; Doping in Sports ; Dose-Response Relationship, Drug ; Drug testing ; EPO ; Erythropoietin - administration & dosage ; Erythropoietin - pharmacology ; Exercise Test ; Female ; Hemoglobins - analysis ; Humans ; Male ; micro‐dosing ; Physiology ; Recombinant Proteins - administration & dosage ; Recombinant Proteins - pharmacology ; Young Adult</subject><ispartof>Drug testing and analysis, 2017-10, Vol.9 (10), p.1561-1571</ispartof><rights>Copyright © 2017 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3836-42fb83da42cadf9ea9bbc6d3fac5d966da28e63629938a7ec4e8514365ba0c693</citedby><cites>FETCH-LOGICAL-c3836-42fb83da42cadf9ea9bbc6d3fac5d966da28e63629938a7ec4e8514365ba0c693</cites><orcidid>0000-0003-2277-0463</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fdta.2176$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fdta.2176$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28214385$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Clark, Brad</creatorcontrib><creatorcontrib>Woolford, Sarah M.</creatorcontrib><creatorcontrib>Eastwood, Annette</creatorcontrib><creatorcontrib>Sharpe, Ken</creatorcontrib><creatorcontrib>Barnes, Peter G.</creatorcontrib><creatorcontrib>Gore, Christopher J.</creatorcontrib><title>Temporal changes in physiology and haematology in response to high‐ and micro‐doses of recombinant human erythropoietin</title><title>Drug testing and analysis</title><addtitle>Drug Test Anal</addtitle><description>There is evidence to suggest athletes have adopted recombinant human erythropoietin (rHuEPO) dosing regimens that diminish the likelihood of being caught by direct detection techniques. However, the temporal response in physiology, performance, and Athlete Biological Passport (ABP) parameters to such regimens is not clearly understood. Participants were assigned to a high‐dose only group (HIGH, n = 8, six rHuEPO doses of 250 IU/kg over two weeks), a combined high micro‐dose group (COMB, n = 8, high‐dose plus nine rHuEPO micro‐doses over a further three weeks), or one of two placebo control groups who received saline in the same pattern as the HIGH (HIGH‐PLACEBO, n = 4) or COMB (COMB‐PLACEBO, n = 4) groups. Temporal changes in physiology and performance were tracked by graded exercise test (GXT) and haemoglobin mass assessment at baseline, after high dose, after micro‐dose (COMB and COMB‐PLACEBO only) and after a four‐week washout. Venous blood samples were collected throughout the baseline, rHuEPO administration, and washout periods to determine the haematological and ABP response to each dosing regimen. Physiological adaptations induced by a two‐week rHuEPO high‐dose were maintained by rHuEPO micro‐dosing for at least three weeks. However, all participants administered rHuEPO registered at least one suspicious ABP value during the administration or washout periods. These results indicate there is sufficient sensitivity in the ABP to detect use of high rHuEPO doping regimens in athletic populations and they provide important empirical examples for use by anti‐doping experts. Copyright © 2017 John Wiley & Sons, Ltd.
The temporal response in physiology, performance and athlete biological passport (ABP) parameters to high or high‐micro recombinant human erythropoietin dosing regimens was assessed in recreational athletes. The physiological adaptations and modest performance improvements induced by a two week rHuEPO high dose were maintained by rHuEPO micro‐dosing for at least three weeks. However, rHuEPO micro‐dosing did not mask previous rHuEPO high‐dosing and all participants administered rHuEPO registered at least one suspicious ABP value during the administration or washout periods.</description><subject>ABP</subject><subject>Adult</subject><subject>Blood Volume - drug effects</subject><subject>doping</subject><subject>Doping in Sports</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug testing</subject><subject>EPO</subject><subject>Erythropoietin - administration & dosage</subject><subject>Erythropoietin - pharmacology</subject><subject>Exercise Test</subject><subject>Female</subject><subject>Hemoglobins - analysis</subject><subject>Humans</subject><subject>Male</subject><subject>micro‐dosing</subject><subject>Physiology</subject><subject>Recombinant Proteins - administration & dosage</subject><subject>Recombinant Proteins - pharmacology</subject><subject>Young Adult</subject><issn>1942-7603</issn><issn>1942-7611</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctu1TAQhiMEoqUg8QTIEhs2Kb4kPvayKlepEpvD2prYkxNXiR3sRCjqhkfgGXkS3J5SJCRWnpE_f_LMX1UvGT1nlPK3boFzznbyUXXKdMPrnWTs8UNNxUn1LOdrSmXDRfu0OuGKs0ao9rS62eM0xwQjsQOEA2biA5mHLfs4xsNGIDgyAE6wHPtymzDPMWQkSySDPwy_fvy8wyZvUyyNi7loYl9AG6fOBwgLGdYJAsG0LUOKc_S4-PC8etLDmPHF_XlWff3wfn_5qb768vHz5cVVbYUSsm543ynhoOEWXK8RdNdZ6UQPtnVaSgdcoRSSay0U7NA2qNoynmw7oFZqcVa9OXrnFL-tmBcz-WxxHCFgXLNhSsldS8vzgr7-B72Oawrld4bpttFlcYr-FZaBc07Ymzn5CdJmGDW3gZgSiLkNpKCv7oVrN6F7AP8kUID6CHz3I27_FZl3-4s74W8aDZhS</recordid><startdate>201710</startdate><enddate>201710</enddate><creator>Clark, Brad</creator><creator>Woolford, Sarah M.</creator><creator>Eastwood, Annette</creator><creator>Sharpe, Ken</creator><creator>Barnes, Peter G.</creator><creator>Gore, Christopher J.</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>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2277-0463</orcidid></search><sort><creationdate>201710</creationdate><title>Temporal changes in physiology and haematology in response to high‐ and micro‐doses of recombinant human erythropoietin</title><author>Clark, Brad ; Woolford, Sarah M. ; Eastwood, Annette ; Sharpe, Ken ; Barnes, Peter G. ; Gore, Christopher J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3836-42fb83da42cadf9ea9bbc6d3fac5d966da28e63629938a7ec4e8514365ba0c693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>ABP</topic><topic>Adult</topic><topic>Blood Volume - drug effects</topic><topic>doping</topic><topic>Doping in Sports</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug testing</topic><topic>EPO</topic><topic>Erythropoietin - administration & dosage</topic><topic>Erythropoietin - pharmacology</topic><topic>Exercise Test</topic><topic>Female</topic><topic>Hemoglobins - analysis</topic><topic>Humans</topic><topic>Male</topic><topic>micro‐dosing</topic><topic>Physiology</topic><topic>Recombinant Proteins - administration & dosage</topic><topic>Recombinant Proteins - pharmacology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Clark, Brad</creatorcontrib><creatorcontrib>Woolford, Sarah M.</creatorcontrib><creatorcontrib>Eastwood, Annette</creatorcontrib><creatorcontrib>Sharpe, Ken</creatorcontrib><creatorcontrib>Barnes, Peter G.</creatorcontrib><creatorcontrib>Gore, Christopher J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Drug testing and analysis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Clark, Brad</au><au>Woolford, Sarah M.</au><au>Eastwood, Annette</au><au>Sharpe, Ken</au><au>Barnes, Peter G.</au><au>Gore, Christopher J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Temporal changes in physiology and haematology in response to high‐ and micro‐doses of recombinant human erythropoietin</atitle><jtitle>Drug testing and analysis</jtitle><addtitle>Drug Test Anal</addtitle><date>2017-10</date><risdate>2017</risdate><volume>9</volume><issue>10</issue><spage>1561</spage><epage>1571</epage><pages>1561-1571</pages><issn>1942-7603</issn><eissn>1942-7611</eissn><abstract>There is evidence to suggest athletes have adopted recombinant human erythropoietin (rHuEPO) dosing regimens that diminish the likelihood of being caught by direct detection techniques. However, the temporal response in physiology, performance, and Athlete Biological Passport (ABP) parameters to such regimens is not clearly understood. Participants were assigned to a high‐dose only group (HIGH, n = 8, six rHuEPO doses of 250 IU/kg over two weeks), a combined high micro‐dose group (COMB, n = 8, high‐dose plus nine rHuEPO micro‐doses over a further three weeks), or one of two placebo control groups who received saline in the same pattern as the HIGH (HIGH‐PLACEBO, n = 4) or COMB (COMB‐PLACEBO, n = 4) groups. Temporal changes in physiology and performance were tracked by graded exercise test (GXT) and haemoglobin mass assessment at baseline, after high dose, after micro‐dose (COMB and COMB‐PLACEBO only) and after a four‐week washout. Venous blood samples were collected throughout the baseline, rHuEPO administration, and washout periods to determine the haematological and ABP response to each dosing regimen. Physiological adaptations induced by a two‐week rHuEPO high‐dose were maintained by rHuEPO micro‐dosing for at least three weeks. However, all participants administered rHuEPO registered at least one suspicious ABP value during the administration or washout periods. These results indicate there is sufficient sensitivity in the ABP to detect use of high rHuEPO doping regimens in athletic populations and they provide important empirical examples for use by anti‐doping experts. Copyright © 2017 John Wiley & Sons, Ltd.
The temporal response in physiology, performance and athlete biological passport (ABP) parameters to high or high‐micro recombinant human erythropoietin dosing regimens was assessed in recreational athletes. The physiological adaptations and modest performance improvements induced by a two week rHuEPO high dose were maintained by rHuEPO micro‐dosing for at least three weeks. However, rHuEPO micro‐dosing did not mask previous rHuEPO high‐dosing and all participants administered rHuEPO registered at least one suspicious ABP value during the administration or washout periods.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28214385</pmid><doi>10.1002/dta.2176</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-2277-0463</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | ABP Adult Blood Volume - drug effects doping Doping in Sports Dose-Response Relationship, Drug Drug testing EPO Erythropoietin - administration & dosage Erythropoietin - pharmacology Exercise Test Female Hemoglobins - analysis Humans Male micro‐dosing Physiology Recombinant Proteins - administration & dosage Recombinant Proteins - pharmacology Young Adult |
title | Temporal changes in physiology and haematology in response to high‐ and micro‐doses of recombinant human erythropoietin |
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