{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T17:15:07Z","timestamp":1784567707815,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,11,8]],"date-time":"2017-11-08T00:00:00Z","timestamp":1510099200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006058","name":"St. Baldrick's Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006058","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1U54HD071598\u201001,"],"award-info":[{"award-number":["1U54HD071598\u201001,"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001377","name":"Walther Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001377","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Vincristine (VCR) is a critical part of treatment in pediatric malignancies and is associated with dose\u2010dependent peripheral neuropathy (vincristine\u2010induced peripheral neuropathy [VIPN]). Our previous findings show VCR metabolism is regulated by the <jats:italic>CYP3A5<\/jats:italic> gene. Individuals who are low <jats:italic>CYP3A5<\/jats:italic> expressers metabolize VCR slower and experience more severe VIPN as compared to high expressers. Preliminary observations suggest that Caucasians experience more severe VIPN as compared to nonCaucasians.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Kenyan children with cancer who were undergoing treatment including VCR were recruited for a prospective cohort study. Patients received IV VCR 2\u00a0mg\/m<jats:sup>2<\/jats:sup>\/dose with a maximum dose of 2.5\u00a0mg as part of standard treatment protocols. VCR pharmacokinetics (PK) sampling was collected via dried blood spot cards and genotyping was conducted for common functional variants in <jats:italic>CYP3A5<\/jats:italic>, multi\u2010drug resistance 1 <jats:italic>(MDR1<\/jats:italic>), <jats:italic>and<\/jats:italic> microtubule\u2010associated protein tau (<jats:italic>MAPT<\/jats:italic>). VIPN was assessed using five neuropathy tools.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The majority of subjects (91%) were <jats:italic>CYP3A5<\/jats:italic> high\u2010expresser genotype. <jats:italic>CYP3A5<\/jats:italic> low\u2010expresser genotype subjects had a significantly higher dose and body surface area normalized area under the curve than <jats:italic>CYP3A5<\/jats:italic> high\u2010expresser genotype subjects (0.28\u00a0\u00b1\u00a00.15\u00a0hr\u00b7m<jats:sup>2<\/jats:sup>\/l vs. 0.15\u00a0\u00b1\u00a00.011\u00a0hr\u00b7m<jats:sup>2<\/jats:sup>\/l, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.027). Regardless of which assessment tool was utilized, minimal neuropathy was detected in this cohort. There was no difference in the presence or severity of neuropathy assessed between <jats:italic>CYP3A5<\/jats:italic> high\u2010 and low\u2010expresser genotype groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Genetic factors are associated with VCR PK. Due to the minimal neuropathy observed in this cohort, there was no demonstrable association between genetic factors or VCR PK with development of VIPN. Further studies are needed to determine the role of genetic factors in optimizing dosing of VCR for maximal benefit.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.26854","type":"journal-article","created":{"date-parts":[[2017,11,8]],"date-time":"2017-11-08T11:08:47Z","timestamp":1510139327000},"source":"Crossref","is-referenced-by-count":40,"title":["<i>CYP3A5<\/i> genotype and its impact on vincristine pharmacokinetics and development of neuropathy in Kenyan children with cancer"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7653-5920","authenticated-orcid":false,"given":"Jodi L.","family":"Skiles","sequence":"first","affiliation":[{"name":"Department of Pediatrics Indiana University School of Medicine  Indianapolis Indiana"},{"name":"School of Medicine Department of Child Health and Paediatrics Moi University College of Health Sciences  Eldoret 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