CYP2C19 Phenotype and Body Weight-Guided Voriconazole Initial Dose in Infants and Children after Hematopoietic Cell Transplantation.

Antimicrobial Agents and Chemotherapy
Takuto TakahashiMark N Kirstein

Abstract

Prophylactic voriconazole use is recommended for children undergoing hematopoietic cell transplantation (HCT). Dosing considerations are essential, due to the narrow therapeutic window of voriconazole. Known covariates do not sufficiently explain the large interindividual pharmacokinetic (PK) variability of voriconazole. Moreover, knowledge of voriconazole PK for age <2 years is limited. We investigated genetic and clinical covariate associations with voriconazole interindividual PK variability and subsequently simulated dosing regimens in children. This study was conducted as part of a single-institution, phase I study of intravenous voriconazole therapy for children undergoing HCT. We conducted a population PK analysis and tested covariate effects on voriconazole PK, including 67 genetic variants and clinical variables. We analyzed plasma voriconazole and N-oxide metabolite concentrations from 58 children <21 years of age (including 12 children <2 years of age). A two-compartment parent mixed linear/nonlinear model best described our data. The CYP2C19 phenotype and body weight were significant covariates (P < 0.05 for both). Our model performance for age <2 years was comparable to that for other age groups. Simulation of the ...Continue Reading

References

Sep 19, 2003·The New England Journal of Medicine·Gregory L KearnsRalph E Kauffman
May 25, 2004·Antimicrobial Agents and Chemotherapy·Thomas J WalshNolan Wood
Jun 24, 2004·Computer Methods and Programs in Biomedicine·Lars LindbomE Niclas Jonsson
Mar 25, 2005·American Journal of Human Genetics·Janis E WiggintonGoncalo R Abecasis
Jul 19, 2005·Computer Methods and Programs in Biomedicine·Lars LindbomNiclas Jonsson
Aug 25, 2006·Clinical Pharmacokinetics·Trevor N JohnsonGeoffrey T Tucker
Jun 7, 2007·European Journal of Pediatrics·Charalampos AntachopoulosEmmanuel Roilides
Jun 20, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Alison E Aitken, Edward T Morgan
Jan 8, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Thomas J WalshUNKNOWN Infectious Diseases Society of America
Nov 27, 2008·Journal of Clinical Pharmacology·Johanna WeissGerd Mikus
Dec 17, 2008·Antimicrobial Agents and Chemotherapy·Mats O KarlssonPeter A Milligan
Dec 3, 2009·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Michael NeelyJill Hoffman
Jun 16, 2010·Antimicrobial Agents and Chemotherapy·Claudia MichaelRainer Preiss
Mar 8, 2011·Drug Discovery Today·Nienke J VetSaskia N de Wildt
Dec 23, 2011·The Journal of Antimicrobial Chemotherapy·Pere Soler-PalacínConcepció Figueras
Mar 21, 2012·Antimicrobial Agents and Chemotherapy·Lena E FribergPing Liu
Nov 2, 2012·Antimicrobial Agents and Chemotherapy·Imke H BartelinkMarc Bierings
May 8, 2013·Journal of Pharmaceutical Sciences·Nick HolfordBrian Anderson
Dec 18, 2014·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·H-R HeJ Lu
Mar 17, 2015·Journal of Gastroenterology·Tomohiro Terada, Daiki Hira
Mar 25, 2015·Clinical Pharmacology and Therapeutics·K A BirdwellI A M MacPhee
Feb 3, 2016·Antimicrobial Agents and Chemotherapy·Luc J HuurnemanWilliam Hope
Oct 7, 2016·Acta Pharmaceutica Sinica. B·Fang XieQing-Yu Zhang
Oct 13, 2016·Journal of Pharmacokinetics and Pharmacodynamics·Anne-Gaëlle DosneMats O Karlsson
Dec 17, 2016·Clinical Pharmacology and Therapeutics·B MoriyamaT J Walsh
Mar 10, 2017·Pharmacogenetics and Genomics·Julia M BarbarinoRuss B Altman
Aug 9, 2017·Clinical Pharmacology and Therapeutics·Thomas DuflotFabien Lamoureux
Oct 19, 2017·Antimicrobial Agents and Chemotherapy·Silke GastineGeorg Hempel
Jun 20, 2018·Pharmacogenomics·Sarah AllegraAntonio D'Avolio
Sep 15, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Miao YanHoan Linh Banh
Mar 20, 2020·Clinical Pharmacology and Therapeutics·Katherine N ThekenTilo Grosser
May 28, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Thomas LehrnbecherLillian Sung
Oct 31, 2020·Pharmacology Research & Perspectives·Sumonrat ChuwongwattanaChonlaphat Sukasem

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genotyping

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