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We evaluated whether BuCL could be predicted by a predose plasma panel of 841 endogenous metabolomic compounds (EMCs). In this prospective cohort of 132 hematopoietic cell transplantation (HCT) patients, all had samples collected immediately before busulfan administration (preBU) and 96 had samples collected 2\u2009weeks before busulfan (2\u2010week\u2010preBU). BuCL was significantly associated with 37 EMCs after univariate linear regression analysis and controlling for false discovery (&lt;\u20090.05) in the 132 preBU samples. In parallel, with preBU samples, we included all 841 EMCs in a least absolute shrinkage and selection operator\u2013penalized regression which selected 13 EMCs as predominantly associated with BuCL. Then, we constructed a prediction model by estimating coefficients for these 13 EMCs, along with sex, using ordinary least\u2010squares. When the resulting linear prediction model was applied to the 2\u2010week\u2010preBU samples, it explained 40% of the variation in BuCL (adjusted\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u00a0=\u00a00.40). Pathway enrichment analysis revealed 18 pathways associated with BuCL. Lysine degradation followed by steroid biosynthesis, which aligned with the univariate analysis, were the top two pathways. BuCL can be predicted before busulfan administration with a linear regression model of 13 EMCs. This pharmacometabolomics method should be prioritized over use of a busulfan test dose or pharmacogenomics to guide busulfan dosing. These results highlight the potential of pharmacometabolomics as a precision medicine tool to improve or replace pharmacokinetics to personalize busulfan doses.\n                  <\/jats:p>","DOI":"10.1002\/cpt.2794","type":"journal-article","created":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T05:04:38Z","timestamp":1668229478000},"page":"370-379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Prediction of Busulfan Clearance by Predose Plasma Metabolomic Profiling"],"prefix":"10.1111","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0795-497X","authenticated-orcid":false,"given":"Jeannine S.","family":"McCune","sequence":"first","affiliation":[{"name":"Department of Hematologic Malignancies Translational Sciences City of Hope  Duarte California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4260-2486","authenticated-orcid":false,"given":"Sandi L.","family":"Navarro","sequence":"additional","affiliation":[{"name":"Public Health Sciences Division Fred Hutchinson Cancer Center  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9207-6162","authenticated-orcid":false,"given":"K. Scott","family":"Baker","sequence":"additional","affiliation":[{"name":"Clinical Research Division Fred Hutchinson Cancer Center  Washington Seattle USA"},{"name":"Department of Pediatrics University of Washington  Washington Seattle USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda J.","family":"Risler","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian R.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8465-1588","authenticated-orcid":false,"given":"Timothy W.","family":"Randolph","sequence":"additional","affiliation":[{"name":"Clinical Research Division Fred Hutchinson Cancer Center  Washington Seattle USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Shireman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8933-8195","authenticated-orcid":false,"given":"H. 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R.","family":"Huitema","sequence":"additional","affiliation":[{"name":"Department of Pharmacy &amp; Pharmacology Netherlands Cancer Institute  Amsterdam The Netherlands"},{"name":"Department of Pharmacology, Princes Maxima &amp; Pharmacology Netherlands Cancer Institute  Amsterdam The Netherlands"},{"name":"Department of Clinical Pharmacy University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,26]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2016.07.013"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2019.05.021"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2011.06.013"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270012447196"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-016-1106-6"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.6b00370"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(88)90161-5"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00689702"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-1960"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.0c00599"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-007-0082-2"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-9868.2010.00740.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab382"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1067"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1089"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btg382"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbl022"},{"key":"e_1_2_9_20_1","unstructured":"Food and Drug Administration.Guidance for Industry: Bioavailability and Bioequivalence Studies for Orally Administered Drug Products \u2014 General Considerations. 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