{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:07:29Z","timestamp":1784549249444,"version":"3.55.0"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Voriconazole has variable pharmacokinetics, significant interactions, and a narrow therapeutic window, requiring drug monitoring. This study evaluated CYP2C19 genotype and voriconazole levels in North Indian children, a population with limited pharmacogenomic data. It is a prospective single\u2010center study (August 2023\u2010January 2025) in children with leukemia\/HSCT. Voriconazole levels were measured using the ARK assay; CYP2C19 genotyping was done by PCR\u2013Sanger, with phenotypes assigned per CPIC guidelines. A total of 102 patients (mean age 6.56 \u00b1 4.22 years; M:F 1.9:1) were enrolled, with B\u2010ALL being most common diagnosis (77.5%). Voriconazole levels showed marked variability, with only 52.9% in the therapeutic range (1\u20105.5 \u00b5g\/mL). Intermediate (33.3%) and normal (30.4%) metabolizers predominated. CYP2C19 genotype correlated significantly with levels (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; \u00a00.001): poor metabolizers (*2\/*2) had the highest concentrations (8.73 \u00b1 2.22), normal (*1\/*1) and intermediate were in the therapeutic range (\u223c3.2 \u00b5g\/mL), and rapid metabolizera had subtherapeutic levels (1.65 \u00b1 3.21). Median levels in *1\/*2 and *2\/*2 were 1.9\u2010 and 5.3\u2010fold higher than in rapid metabolizers. Hepatotoxicity, defined as ALT\/AST \u22655\u00d7 ULN or \u22653\u00d7 ULN with symptoms or hyperbilirubinemia, occurred in 28.4% and was significantly associated with supratherapeutic levels; toxicity correlated more strongly with drug exposure than with CYP2C19 genotype alone. Multivariate analysis identified genotype (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; \u00a00.001) and dose (\n                    <jats:italic>P<\/jats:italic>\n                    = \u00a00.0021) as key determinants of drug levels, whereas age, gender, and weight were not significant. This prospective study shows a strong link between CYP2C19 genotype and voriconazole exposure in children, supporting genotype\u2010guided dosing with therapeutic drug monitoring and highlighting the need for ancestry\u2010informed precision dosing.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70198","type":"journal-article","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T05:20:46Z","timestamp":1778304046000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacogenomic Profiling of Voriconazole Enables Predicting Its Toxicity in Pediatric Leukemia and Hematopoietic Stem Cell Transplant Recipients\u2014A Prospective Study From North India"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4042-6415","authenticated-orcid":false,"given":"Ankita","family":"Chakraborty","sequence":"first","affiliation":[{"name":"Pediatric Hematology\u2013Oncology and BMT unit Sir Ganga Ram Hospital New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2570-7750","authenticated-orcid":false,"given":"Manas","family":"Kalra","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\u2013Oncology and BMT unit Sir Ganga Ram Hospital New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renu","family":"Saxena","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Raj","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seema","family":"Bhargava","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Sir Ganga Ram Hospital  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali","family":"Manocha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Sir Ganga Ram Hospital  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupam","family":"Sachdeva","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\u2013Oncology and BMT unit Sir Ganga Ram Hospital New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"The Harriet Lane Handbook: A Manual for Pediatric House Officers","author":"Tschudy MM","year":"2023"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.583"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11096-015-0143-y"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000014137"},{"key":"e_1_2_11_6_1","first-page":"190","article-title":"Impact of CYP2C19 genotype on voriconazole exposure in pediatric patients","volume":"17","author":"Hu X","year":"2023","journal-title":"Front Pharmacol"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0b013e3182880eaa"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00955-18"},{"key":"e_1_2_11_9_1","article-title":"CYP2C19\u2010guided voriconazole dosing in hematopoietic cell transplant recipients","author":"Patel JN","year":"2023","journal-title":"Clin Infect Dis"},{"key":"e_1_2_11_10_1","article-title":"Genotype\u2010informed voriconazole dosing improves therapeutic target attainment","author":"Lee S","year":"2025","journal-title":"Clin Transl Sci"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0000000000000464"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.14.53"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/myc.13293"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1078155210397963"},{"key":"e_1_2_11_15_1","article-title":"Voriconazole therapy and CYP2C19 genotype","author":"Dean L","year":"2019","journal-title":"Medical Genetics Summaries"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028020948174"},{"key":"e_1_2_11_17_1","article-title":"Population pharmacokinetics of voriconazole in pediatric malignancy integrating CYP2C19 phenotype","author":"Shoji S","year":"2024","journal-title":"J Infect Chemother"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dku529"},{"key":"e_1_2_11_19_1","article-title":"Clinical impact of CYP2C19\u2010guided voriconazole therapy on toxicity outcomes","author":"Katada Y","year":"2025","journal-title":"Pharmacogenomics J"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12291-015-0507-z"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24262"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/mmy\/myz006"}],"container-title":["The Journal of Clinical 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