{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T01:06:11Z","timestamp":1778979971946,"version":"3.51.4"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,11,15]],"date-time":"2018-11-15T00:00:00Z","timestamp":1542240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mercaptopurine is a drug commonly used in the treatment of different types of cancer, especially acute lymphoblastic leukaemia, and autoimmune diseases such as ulcerative colitis or Crohn's disease and in patients receiving organ transplants. It is metabolized by three cytosolic enzymes. One of them, thiopurine S\u2010methyltransferase (<jats:styled-content style=\"fixed-case\">TPMT<\/jats:styled-content>), is responsible for catalysing the methylation reaction of mercaptopurine to 6\u2010methylmercaptopurine, thus inactivating the drug. Individuals with <jats:italic><jats:styled-content style=\"fixed-case\">TPMT<\/jats:styled-content><\/jats:italic> loss\u2010of\u2010function alleles (*2, *3A, *3B or *3C) can be extremely sensitive to the effect of mercaptopurine, since it can be accumulated, therefore producing haematological toxicity. The objective of this study was to evaluate the role of <jats:italic><jats:styled-content style=\"fixed-case\">TPMT<\/jats:styled-content><\/jats:italic> polymorphisms on the pharmacokinetics of mercaptopurine. For that purpose, we used collected pharmacokinetic data from 48 healthy volunteers (all males) who received a single oral dose of mercaptopurine 50 mg in two bioequivalence studies. The volunteers were subsequently genotyped for <jats:italic><jats:styled-content style=\"fixed-case\">TPMT<\/jats:styled-content><\/jats:italic> *2, *3A, *3B and *3C alleles by real\u2010time <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>. There were four carriers (8.3%) of <jats:italic><jats:styled-content style=\"fixed-case\">TPMT<\/jats:styled-content><\/jats:italic>*2 and <jats:italic><jats:styled-content style=\"fixed-case\">TPMT<\/jats:styled-content><\/jats:italic>*3A alleles. Mercaptopurine elimination was affected by <jats:italic><jats:styled-content style=\"fixed-case\">TPMT<\/jats:styled-content><\/jats:italic> loss\u2010of\u2010function polymorphisms, since heterozygous subjects show 18% higher half\u2010life compared to wild\u2010type individuals. This fact is consistent with the expected since the presence of loss\u2010of\u2010function alleles decreases <jats:italic><jats:styled-content style=\"fixed-case\">TPMT<\/jats:styled-content><\/jats:italic> enzymatic activity and, thus, affects mercaptopurine elimination. Moreover, mercaptopurine pharmacokinetic parameters were different among races, since Latins showed higher plasma concentrations and lower clearance compared to Caucasians. This fact might be due to a different distribution of polymorphisms in genes, other than <jats:italic><jats:styled-content style=\"fixed-case\">TPMT<\/jats:styled-content><\/jats:italic>, that also influence the pharmacokinetics of mercaptopurine.<\/jats:p>","DOI":"10.1111\/bcpt.13153","type":"journal-article","created":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T13:15:51Z","timestamp":1540214151000},"page":"449-455","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Influence of thiopurine S\u2010methyltransferase polymorphisms in mercaptopurine pharmacokinetics in healthy volunteers"],"prefix":"10.1111","volume":"124","author":[{"given":"Miriam","family":"Saiz\u2010Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Department Instituto Te\u00f3filo Hernando Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Universidad Aut\u00f3noma de Madrid (UAM) Hospital Universitario de La Princesa Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dolores","family":"Ochoa","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Instituto Te\u00f3filo Hernando Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Universidad Aut\u00f3noma de Madrid (UAM) Hospital Universitario de La Princesa Madrid Spain"},{"name":"UICEC Hospital Universitario de La Princesa Plataforma SCReN (Spanish Clinical Research Network) Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Belmonte","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Instituto Te\u00f3filo Hernando Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Universidad Aut\u00f3noma de Madrid (UAM) Hospital Universitario de La Princesa Madrid Spain"},{"name":"UICEC Hospital Universitario de La Princesa Plataforma SCReN (Spanish Clinical Research Network) Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Rom\u00e1n","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Instituto Te\u00f3filo Hernando Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Universidad Aut\u00f3noma de Madrid (UAM) Hospital Universitario de La Princesa Madrid Spain"},{"name":"UICEC Hospital Universitario de La Princesa Plataforma SCReN (Spanish Clinical Research Network) Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Mart\u00ednez\u2010Ingelmo","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Instituto Te\u00f3filo Hernando Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Universidad Aut\u00f3noma de Madrid (UAM) Hospital Universitario de La Princesa Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc\u00eda","family":"Ortega\u2010Ru\u00edz","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Instituto Te\u00f3filo Hernando Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Universidad Aut\u00f3noma de Madrid (UAM) Hospital Universitario de La Princesa Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Sarmiento\u2010Iglesias","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Instituto Te\u00f3filo Hernando Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Universidad Aut\u00f3noma de Madrid (UAM) Hospital Universitario de La Princesa Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coral","family":"Herrador","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Instituto Te\u00f3filo Hernando Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Universidad Aut\u00f3noma de Madrid (UAM) Hospital Universitario de La Princesa Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Abad\u2010Santos","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Instituto Te\u00f3filo Hernando Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Universidad Aut\u00f3noma de Madrid (UAM) Hospital Universitario de La Princesa Madrid Spain"},{"name":"UICEC Hospital Universitario de La Princesa Plataforma SCReN (Spanish Clinical Research Network) Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Instituto de Salud Carlos III Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.09.78"},{"key":"e_1_2_8_3_1","unstructured":"U.S. Food & Drug Administration (FDA).Label information for mercaptopurine.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2011\/009053s032lbl.pdf. Accessed August 14 2018."},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740330903426151"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70140-5"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.14.32"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-299"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.4"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2006.05.011"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198304283081705"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2008.03281.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1258\/0004563041201455"},{"issue":"69","key":"e_1_2_8_13_1","first-page":"399","article-title":"Choice of azathioprine or 6\u2010mercaptopurine dose based on thiopurine methyltransferase (TPMT) activity to avoid myelosuppression. A prospective study","volume":"53","author":"Gisbert JP","year":"2006","journal-title":"Hepatogastroenterology"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920012803341311"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2007.03301.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e328334338f"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.4671"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3060"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3508"}],"container-title":["Basic &amp; Clinical Pharmacology &amp; Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcpt.13153","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.13153","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcpt.13153","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.13153","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T10:56:47Z","timestamp":1694429807000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcpt.13153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,15]]},"references-count":18,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1111\/bcpt.13153"],"URL":"https:\/\/doi.org\/10.1111\/bcpt.13153","archive":["Portico"],"relation":{},"ISSN":["1742-7835","1742-7843"],"issn-type":[{"value":"1742-7835","type":"print"},{"value":"1742-7843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,15]]},"assertion":[{"value":"2018-08-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}