PMID- 37553971 OWN - NLM STAT- MEDLINE DCOM- 20231004 LR - 20231004 IS - 1439-0507 (Electronic) IS - 0933-7407 (Linking) VI - 66 IP - 11 DP - 2023 Nov TI - Voriconazole plasma concentrations and dosing in paediatric patients below 24 months of age. PG - 969-976 LID - 10.1111/myc.13643 [doi] AB - Voriconazole (VCZ) is an important first-line option for management of invasive fungal diseases and approved in paediatric patients >/=24 months at distinct dosing schedules that consider different developmental stages. Information on dosing and exposures in children <24 months of age is scarce. Here we report our experience in children <24 months who received VCZ due to the lack of alternative treatment options. This retrospective analysis includes 50 distinct treatment episodes in 17 immunocompromised children aged between 3 and <24 months, who received VCZ between 2004 and 2022 as prophylaxis (14 patients; 47 episodes) or as empirical treatment (3 patients; 3 episodes) by mouth (46 episodes) or intravenously (4 episodes) based on contraindications, intolerance or lack of alternative options. Trough concentrations were measured as clinically indicated, and tolerability was assessed based on hepatic function parameters and discontinuations due to adverse events (AEs). VCZ was administered for a median duration of 10 days (range: 1-138). Intravenous doses ranged from 4.9 to 7.0 mg/kg (median: 6.5) twice daily, and oral doses from 3.8 to 29 mg/kg (median: 9.5) twice daily, respectively. The median trough concentration was 0.63 mg/L (range: 0.01-16.2; 38 samples). Only 34.2% of samples were in the recommended target range of 1-6 mg/L; 57.9% had lower and 7.9% higher trough concentrations. Hepatic function parameters analysed at baseline, during treatment and at end of treatment did not show significant changes during VCZ treatment. There was no correlation between dose and exposure or hepatic function parameters. In three episodes, VCZ was discontinued due to an AE (6%; three patients). In conclusion, this retrospective analysis reveals no signal for increased toxicity in paediatric patients <24 months of age. Empirical dosing resulted in mostly subtherapeutic exposures which emphasises the need for more systematic study of the pharmacokinetics of VCZ in this age group. CI - (c) 2023 The Authors. Mycoses published by Wiley-VCH GmbH. FAU - Gastine, Silke E AU - Gastine SE AD - Institute of Pharmaceutical and Medical Chemistry - Department of Clinical Pharmacy, Westphalian Wilhelms University Munster, Munster, Germany. FAU - Rauwolf, Kerstin K AU - Rauwolf KK AUID- ORCID: 0000-0002-9778-0669 AD - Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, Children's University Hospital Munster, Munster, Germany. FAU - Pieper, Stephanie AU - Pieper S AD - Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, Children's University Hospital Munster, Munster, Germany. FAU - Hempel, Georg AU - Hempel G AD - Institute of Pharmaceutical and Medical Chemistry - Department of Clinical Pharmacy, Westphalian Wilhelms University Munster, Munster, Germany. FAU - Lehrnbecher, Thomas AU - Lehrnbecher T AD - Division of Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe University Frankfurt, Frankfurt, Germany. FAU - Tragiannidis, Athanasios AU - Tragiannidis A AD - Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, Children's University Hospital Munster, Munster, Germany. AD - 2nd Department of Pediatrics, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece. FAU - Groll, Andreas H AU - Groll AH AUID- ORCID: 0000-0003-1188-393X AD - Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, Children's University Hospital Munster, Munster, Germany. LA - eng PT - Journal Article DEP - 20230808 PL - Germany TA - Mycoses JT - Mycoses JID - 8805008 RN - JFU09I87TR (Voriconazole) RN - 0 (Antifungal Agents) SB - IM MH - Humans MH - Child MH - Infant MH - Voriconazole/adverse effects MH - *Antifungal Agents/therapeutic use MH - Retrospective Studies MH - *Invasive Fungal Infections/drug therapy MH - Immunocompromised Host OTO - NOTNLM OT - drug monitoring OT - mycoses OT - pediatrics OT - prophylaxis OT - treatment OT - voriconazole EDAT- 2023/08/09 06:43 MHDA- 2023/10/04 06:44 CRDT- 2023/08/09 02:43 PHST- 2023/07/11 00:00 [revised] PHST- 2023/05/05 00:00 [received] PHST- 2023/07/28 00:00 [accepted] PHST- 2023/10/04 06:44 [medline] PHST- 2023/08/09 06:43 [pubmed] PHST- 2023/08/09 02:43 [entrez] AID - 10.1111/myc.13643 [doi] PST - ppublish SO - Mycoses. 2023 Nov;66(11):969-976. doi: 10.1111/myc.13643. Epub 2023 Aug 8.