Comparison of pharmacokinetics and safety of voriconazole intravenous-to-oral switch in immunocompromised children and healthy adults

Timothy A. Driscoll, Lolie C. Yu, Haydar Frangoul, Robert A. Krance, Eneida Nemecek, Jeffrey Blumer, Antonio Arrieta, Michael L. Graham, Scott M. Bradfield, Alice Baruch, Ping Liu

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Voriconazole pharmacokinetics are not well characterized in children despite prior studies. To assess the appropriate pediatric dosing, a study was conducted in 40 immunocompromised children aged 2 to 0-12) was calculated using the noncompartmental method and compared to that for adults receiving approved dosing regimens (6→4 mg/kg IV q12h, 200 mg PO q12h). On average, the AUC 0-12 in children receiving 7 mg/kg IV q12h on day 1 and at IV steady state were 7.85 and 21.4 μg·h/ml, respectively, and approximately 44% and 40% lower, respectively, than those for adults at 6→4 mg/kg IV q12h. Large intersubject variability was observed. At steady state during oral treatment (200 mg q12h), children had higher average exposure than adults, with much larger intersubject variability. The exposure achieved with oral dosing in children tended to decrease as weight and age increased. The most common treatment-related adverse events were transient elevated liver function tests. No clear threshold of voriconazole exposure was identified that would predict the occurrence of treatment-related hepatic events. Overall, voriconazole IV doses higher than 7 mg/kg are needed in children to closely match adult exposures, and a weight-based oral dose may be more appropriate for children than a fixed dose. Safety of voriconazole in children was consistent with the known safety profile of voriconazole.

Original languageEnglish (US)
Pages (from-to)5770-5779
Number of pages10
JournalAntimicrobial Agents and Chemotherapy
Volume55
Issue number12
DOIs
StatePublished - Dec 2011

Fingerprint

Pharmacokinetics
Safety
Weights and Measures
Voriconazole
Liver Function Tests
Area Under Curve
Therapeutics
Pediatrics
Liver

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

Comparison of pharmacokinetics and safety of voriconazole intravenous-to-oral switch in immunocompromised children and healthy adults. / Driscoll, Timothy A.; Yu, Lolie C.; Frangoul, Haydar; Krance, Robert A.; Nemecek, Eneida; Blumer, Jeffrey; Arrieta, Antonio; Graham, Michael L.; Bradfield, Scott M.; Baruch, Alice; Liu, Ping.

In: Antimicrobial Agents and Chemotherapy, Vol. 55, No. 12, 12.2011, p. 5770-5779.

Research output: Contribution to journalArticle

Driscoll, TA, Yu, LC, Frangoul, H, Krance, RA, Nemecek, E, Blumer, J, Arrieta, A, Graham, ML, Bradfield, SM, Baruch, A & Liu, P 2011, 'Comparison of pharmacokinetics and safety of voriconazole intravenous-to-oral switch in immunocompromised children and healthy adults', Antimicrobial Agents and Chemotherapy, vol. 55, no. 12, pp. 5770-5779. https://doi.org/10.1128/AAC.00531-11
Driscoll, Timothy A. ; Yu, Lolie C. ; Frangoul, Haydar ; Krance, Robert A. ; Nemecek, Eneida ; Blumer, Jeffrey ; Arrieta, Antonio ; Graham, Michael L. ; Bradfield, Scott M. ; Baruch, Alice ; Liu, Ping. / Comparison of pharmacokinetics and safety of voriconazole intravenous-to-oral switch in immunocompromised children and healthy adults. In: Antimicrobial Agents and Chemotherapy. 2011 ; Vol. 55, No. 12. pp. 5770-5779.
@article{503067d8bde84045863b29b360818a68,
title = "Comparison of pharmacokinetics and safety of voriconazole intravenous-to-oral switch in immunocompromised children and healthy adults",
abstract = "Voriconazole pharmacokinetics are not well characterized in children despite prior studies. To assess the appropriate pediatric dosing, a study was conducted in 40 immunocompromised children aged 2 to 0-12) was calculated using the noncompartmental method and compared to that for adults receiving approved dosing regimens (6→4 mg/kg IV q12h, 200 mg PO q12h). On average, the AUC 0-12 in children receiving 7 mg/kg IV q12h on day 1 and at IV steady state were 7.85 and 21.4 μg·h/ml, respectively, and approximately 44{\%} and 40{\%} lower, respectively, than those for adults at 6→4 mg/kg IV q12h. Large intersubject variability was observed. At steady state during oral treatment (200 mg q12h), children had higher average exposure than adults, with much larger intersubject variability. The exposure achieved with oral dosing in children tended to decrease as weight and age increased. The most common treatment-related adverse events were transient elevated liver function tests. No clear threshold of voriconazole exposure was identified that would predict the occurrence of treatment-related hepatic events. Overall, voriconazole IV doses higher than 7 mg/kg are needed in children to closely match adult exposures, and a weight-based oral dose may be more appropriate for children than a fixed dose. Safety of voriconazole in children was consistent with the known safety profile of voriconazole.",
author = "Driscoll, {Timothy A.} and Yu, {Lolie C.} and Haydar Frangoul and Krance, {Robert A.} and Eneida Nemecek and Jeffrey Blumer and Antonio Arrieta and Graham, {Michael L.} and Bradfield, {Scott M.} and Alice Baruch and Ping Liu",
year = "2011",
month = "12",
doi = "10.1128/AAC.00531-11",
language = "English (US)",
volume = "55",
pages = "5770--5779",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "12",

}

TY - JOUR

T1 - Comparison of pharmacokinetics and safety of voriconazole intravenous-to-oral switch in immunocompromised children and healthy adults

AU - Driscoll, Timothy A.

AU - Yu, Lolie C.

AU - Frangoul, Haydar

AU - Krance, Robert A.

AU - Nemecek, Eneida

AU - Blumer, Jeffrey

AU - Arrieta, Antonio

AU - Graham, Michael L.

AU - Bradfield, Scott M.

AU - Baruch, Alice

AU - Liu, Ping

PY - 2011/12

Y1 - 2011/12

N2 - Voriconazole pharmacokinetics are not well characterized in children despite prior studies. To assess the appropriate pediatric dosing, a study was conducted in 40 immunocompromised children aged 2 to 0-12) was calculated using the noncompartmental method and compared to that for adults receiving approved dosing regimens (6→4 mg/kg IV q12h, 200 mg PO q12h). On average, the AUC 0-12 in children receiving 7 mg/kg IV q12h on day 1 and at IV steady state were 7.85 and 21.4 μg·h/ml, respectively, and approximately 44% and 40% lower, respectively, than those for adults at 6→4 mg/kg IV q12h. Large intersubject variability was observed. At steady state during oral treatment (200 mg q12h), children had higher average exposure than adults, with much larger intersubject variability. The exposure achieved with oral dosing in children tended to decrease as weight and age increased. The most common treatment-related adverse events were transient elevated liver function tests. No clear threshold of voriconazole exposure was identified that would predict the occurrence of treatment-related hepatic events. Overall, voriconazole IV doses higher than 7 mg/kg are needed in children to closely match adult exposures, and a weight-based oral dose may be more appropriate for children than a fixed dose. Safety of voriconazole in children was consistent with the known safety profile of voriconazole.

AB - Voriconazole pharmacokinetics are not well characterized in children despite prior studies. To assess the appropriate pediatric dosing, a study was conducted in 40 immunocompromised children aged 2 to 0-12) was calculated using the noncompartmental method and compared to that for adults receiving approved dosing regimens (6→4 mg/kg IV q12h, 200 mg PO q12h). On average, the AUC 0-12 in children receiving 7 mg/kg IV q12h on day 1 and at IV steady state were 7.85 and 21.4 μg·h/ml, respectively, and approximately 44% and 40% lower, respectively, than those for adults at 6→4 mg/kg IV q12h. Large intersubject variability was observed. At steady state during oral treatment (200 mg q12h), children had higher average exposure than adults, with much larger intersubject variability. The exposure achieved with oral dosing in children tended to decrease as weight and age increased. The most common treatment-related adverse events were transient elevated liver function tests. No clear threshold of voriconazole exposure was identified that would predict the occurrence of treatment-related hepatic events. Overall, voriconazole IV doses higher than 7 mg/kg are needed in children to closely match adult exposures, and a weight-based oral dose may be more appropriate for children than a fixed dose. Safety of voriconazole in children was consistent with the known safety profile of voriconazole.

UR - http://www.scopus.com/inward/record.url?scp=81555200423&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=81555200423&partnerID=8YFLogxK

U2 - 10.1128/AAC.00531-11

DO - 10.1128/AAC.00531-11

M3 - Article

C2 - 21968355

AN - SCOPUS:81555200423

VL - 55

SP - 5770

EP - 5779

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 12

ER -