Publication: Clinical Pharmacokinetics and Dose Recommendations for Posaconazole in Infants and Children
Issued Date
2019-01-17
Resource Type
ISSN
11791926
03125963
03125963
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2-s2.0-85045727401
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Mahidol University
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SCOPUS
Bibliographic Citation
Clinical Pharmacokinetics. Vol.58, No.1 (2019), 53-61
Suggested Citation
Sophida Boonsathorn, Iek Cheng, Frank Kloprogge, Carlos Alonso, Charmion Lee, Bilyana Doncheva, John Booth, Robert Chiesa, Adam Irwin, Joseph F. Standing Clinical Pharmacokinetics and Dose Recommendations for Posaconazole in Infants and Children. Clinical Pharmacokinetics. Vol.58, No.1 (2019), 53-61. doi:10.1007/s40262-018-0658-1 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/51959
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Title
Clinical Pharmacokinetics and Dose Recommendations for Posaconazole in Infants and Children
Abstract
© 2018, The Author(s). Objectives: The objectives of this study were to investigate the population pharmacokinetics of posaconazole in immunocompromised children, evaluate the influence of patient characteristics on posaconazole exposure and perform simulations to recommend optimal starting doses. Methods: Posaconazole plasma concentrations from paediatric patients undergoing therapeutic drug monitoring were extracted from a tertiary paediatric hospital database. These were merged with covariates collected from electronic sources and case-note reviews. An allometrically scaled population-pharmacokinetic model was developed to investigate the effect of tablet and suspension relative bioavailability, nonlinear bioavailability of suspension, followed by a step-wise covariate model building exercise to identify other important sources of variability. Results: A total of 338 posaconazole plasma concentrations samples were taken from 117 children aged 5 months to 18 years. A one-compartment model was used, with tablet apparent clearance standardised to a 70-kg individual of 15 L/h. Suspension was found to have decreasing bioavailability with increasing dose; the estimated suspension dose to yield half the tablet bioavailability was 99 mg/m 2 . Diarrhoea and proton pump inhibitors were also associated with reduced suspension bioavailability. Conclusions: In the largest population-pharmacokinetic study to date in children, we have found similar covariate effects to those seen in adults, but low bioavailability of suspension in patients with diarrhoea or those taking concurrent proton pump inhibitors, which may in particular limit the use of posaconazole in these patients.