{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T23:38:58Z","timestamp":1781653138267,"version":"3.54.5"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    <jats:italic>Scedosporium apiospermum<\/jats:italic>\n                    is an opportunistic fungal pathogen that causes various infections in immunocompromised patients. Voriconazole is the first\u2010line treatment; however, its clinical use is often challenging due to complex pharmacokinetics and significant interpatient variability, primarily driven by polymorphisms in the CYP450 (CYP2C19) enzymes. These genetic variations affect drug metabolism, resulting in suboptimal drug levels or increased toxicity. We present a case of atraumatic localized\n                    <jats:italic>Scedosporium apiospermum<\/jats:italic>\n                    mycetoma on the back of a patient with a renal transplant. The patient underwent surgical excision and was initiated on voriconazole with a loading dose of 400\u2009mg (6\u2009mg\/kg) every 12\u2009h on day one, followed by 200\u2009mg every 12\u2009h (4\u2009mg\/kg twice daily). Despite dose adjustments, voriconazole serum levels remained persistently sub\u2010therapeutic. Pharmacokinetic and pharmacogenetic studies were conducted for further evaluation. Pharmacokinetic analysis revealed a shortened voriconazole half\u2010life. Pharmacogenetic testing identified a CYP2C19 *1\/*17 genotype, indicating a rapid metaboliser phenotype. This resulted in accelerated drug metabolism, low serum levels and an increased risk of treatment failure and disease progression. Alternative agents to voriconazole, independent of CYP2C19 (isavuconazole, liposomal amphotericin B or posaconazole) were recommended for current and future therapy. Pharmacogenetic and pharmacokinetic testing may play a role in optimizing antifungal therapy. CYP2C19 polymorphisms significantly affect voriconazole metabolism. Patients that are poor metabolisers have greater drug exposure compared with rapid metabolisers. Genotyping may help guide dosage adjustments, predict potential drug interactions and improve treatment efficacy whilst reducing adverse effects. The integration of pharmacogenomic testing, along with therapeutic drug monitoring (TDM), can enhance individualized therapy for both antifungal treatment and prophylaxis in complex clinical scenarios.\n                  <\/jats:p>","DOI":"10.1002\/bcp.70320","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T05:26:32Z","timestamp":1761888392000},"page":"305-311","source":"Crossref","is-referenced-by-count":1,"title":["Navigating therapeutic challenges: Voriconazole pharmacokinetics and CYP2C19 genetic polymorphism\u2014A case report and literature review"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4449-5829","authenticated-orcid":false,"given":"Sadaf","family":"Ahmer","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases Royal North Shore Hospital  St Leonards NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Bui","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Royal North Shore Hospital  St Leonards NSW Australia"},{"name":"Department of Pharmacy Royal North Shore Hospital  St Leonards NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pirathaban","family":"Sivabalan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Wyong Hospital  Hamlyn Terrace NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Kotsiou","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Royal North Shore Hospital  St Leonards NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(20)30784\u20102"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s15010\u2010025\u201002609\u20106"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/imj.15587"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/367934"},{"key":"e_1_2_7_6_1","unstructured":"Pfizer Australia Pty Ltd.Voriconazole Product Information (4 July 2013) Therapeutic Goods Administration AusPAR: Voriconazole|Therapeutic Goods Administration (TGA)."},{"key":"e_1_2_7_7_1","unstructured":"Scedosporium#scedosporium\u2010apiospermum.https:\/\/www.adelaide.edu.au\/mycology\/fungal-descriptions-and-antifungal-susceptibility\/hyphomycetes-conidial-moulds\/scedosporium#scedosporium-apiospermum"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/imj.15592"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof7010023"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469\u20100691.2009.02802.x"},{"issue":"6","key":"e_1_2_7_11_1","first-page":"e193","article-title":"Candida and invasive mould diseases in non\u2010neutropenic critically ill patients and patients with haematological cancer","volume":"22","author":"Colombo AL","year":"2022","journal-title":"Lancet Infect Dis"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofad059"},{"issue":"1","key":"e_1_2_7_13_1","article-title":"Clinical relevance and antifungal susceptibility profiles of Scedosporium spp. and Lomentospora clinical isolates: a comprehensive 2024 analysis","volume":"62","author":"Lackner M","year":"2024","journal-title":"J Clin Microbiol"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkae381"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/13693780802524506"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00039\u201007"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/43.1.149"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01244\u201019"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw326"},{"key":"e_1_2_7_20_1","first-page":"436","article-title":"The eye as target of adverse ocular drug reactions. 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