Atazanavir and atazanavir/ritonavir pharmacokinetics in HIV-infected infants, children, and adolescents

Jennifer J. Kiser, Richard M. Rutstein, Pearl Samson, Bobbie Graham, Grace Aldrovandi, Lynne M. Mofenson, Elizabeth Smith, Steven Schnittman, Terry Fenton, Richard C. Brundage, Courtney V Fletcher

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Objective: To describe the pharmacokinetics of atazanavir (ATV) and ritonavir-boosted ATV (ATV/r) in children aged 91 days to 21 years. Design: A phase I/II, open-label, multicenter study of once-daily ATV and ATV/r as part of combination antiretroviral treatment in HIV-infected treatment-experienced and treatment-naive children. Setting: Sites in the United States and South Africa. Participants: One hundred and ninety-five children enrolled; 172 had evaluable ATV pharmacokinetics on day 7. Intervention: Children were entered in age, dose, and formulation (powder or capsule) cohorts. Intensive pharmacokinetic sampling occurred 7 days after starting ATV. ATV doses were increased or decreased if the 24-h area under the concentration time curves (AUC0-24hr) were less than 30 or more than 90μg×h/ml, respectively. Main Outcomes: Cohorts satisfied protocol-defined pharmacokinetic criteria if the median ATV AUC0-24hr was 60μg×h/ml or less, and AUC0-24hr and ATV concentrations 24-h postdose (C24) were more than 30μg×h/ml and at least 60ng/ml, respectively, in at least 80% of the children, with no individual AUC0-24hr less than 15μg×h/ml. Results: Unboosted ATV capsules satisfied pharmacokinetic criteria at a dose of 520mg/m for those aged more than 2 to 13 years or less and 620mg/m for those aged more than 13 to 21 years or less. ATV/r capsules satisfied criteria at a dose of 205mg/m for those aged more than 2 to 21 years or less. ATV/r powder satisfied criteria at a dose of 310mg/m for those aged more than 2 to 13 years or less, but pharmacokinetics in those aged 2 years or less were highly variable. Conclusion: Body surface area-determined doses of ATV capsules and of ATV/r powder and capsules provide ATV exposures in children of more than 2 years that approximate concentrations in adults receiving ATV/r.

Original languageEnglish (US)
Pages (from-to)1489-1496
Number of pages8
JournalAIDS
Volume25
Issue number12
DOIs
StatePublished - Jul 31 2011

Fingerprint

Ritonavir
Pharmacokinetics
HIV
Capsules
Powders
Atazanavir Sulfate
Body Surface Area

Keywords

  • HIV
  • atazanavir
  • children
  • pediatrics
  • pharmacokinetics
  • protease inhibitor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Kiser, J. J., Rutstein, R. M., Samson, P., Graham, B., Aldrovandi, G., Mofenson, L. M., ... Fletcher, C. V. (2011). Atazanavir and atazanavir/ritonavir pharmacokinetics in HIV-infected infants, children, and adolescents. AIDS, 25(12), 1489-1496. https://doi.org/10.1097/QAD.0b013e328348fc41

Atazanavir and atazanavir/ritonavir pharmacokinetics in HIV-infected infants, children, and adolescents. / Kiser, Jennifer J.; Rutstein, Richard M.; Samson, Pearl; Graham, Bobbie; Aldrovandi, Grace; Mofenson, Lynne M.; Smith, Elizabeth; Schnittman, Steven; Fenton, Terry; Brundage, Richard C.; Fletcher, Courtney V.

In: AIDS, Vol. 25, No. 12, 31.07.2011, p. 1489-1496.

Research output: Contribution to journalArticle

Kiser, JJ, Rutstein, RM, Samson, P, Graham, B, Aldrovandi, G, Mofenson, LM, Smith, E, Schnittman, S, Fenton, T, Brundage, RC & Fletcher, CV 2011, 'Atazanavir and atazanavir/ritonavir pharmacokinetics in HIV-infected infants, children, and adolescents', AIDS, vol. 25, no. 12, pp. 1489-1496. https://doi.org/10.1097/QAD.0b013e328348fc41
Kiser JJ, Rutstein RM, Samson P, Graham B, Aldrovandi G, Mofenson LM et al. Atazanavir and atazanavir/ritonavir pharmacokinetics in HIV-infected infants, children, and adolescents. AIDS. 2011 Jul 31;25(12):1489-1496. https://doi.org/10.1097/QAD.0b013e328348fc41
Kiser, Jennifer J. ; Rutstein, Richard M. ; Samson, Pearl ; Graham, Bobbie ; Aldrovandi, Grace ; Mofenson, Lynne M. ; Smith, Elizabeth ; Schnittman, Steven ; Fenton, Terry ; Brundage, Richard C. ; Fletcher, Courtney V. / Atazanavir and atazanavir/ritonavir pharmacokinetics in HIV-infected infants, children, and adolescents. In: AIDS. 2011 ; Vol. 25, No. 12. pp. 1489-1496.
@article{c5f7c62a8c9c4dd789fb915f6b10ca8d,
title = "Atazanavir and atazanavir/ritonavir pharmacokinetics in HIV-infected infants, children, and adolescents",
abstract = "Objective: To describe the pharmacokinetics of atazanavir (ATV) and ritonavir-boosted ATV (ATV/r) in children aged 91 days to 21 years. Design: A phase I/II, open-label, multicenter study of once-daily ATV and ATV/r as part of combination antiretroviral treatment in HIV-infected treatment-experienced and treatment-naive children. Setting: Sites in the United States and South Africa. Participants: One hundred and ninety-five children enrolled; 172 had evaluable ATV pharmacokinetics on day 7. Intervention: Children were entered in age, dose, and formulation (powder or capsule) cohorts. Intensive pharmacokinetic sampling occurred 7 days after starting ATV. ATV doses were increased or decreased if the 24-h area under the concentration time curves (AUC0-24hr) were less than 30 or more than 90μg×h/ml, respectively. Main Outcomes: Cohorts satisfied protocol-defined pharmacokinetic criteria if the median ATV AUC0-24hr was 60μg×h/ml or less, and AUC0-24hr and ATV concentrations 24-h postdose (C24) were more than 30μg×h/ml and at least 60ng/ml, respectively, in at least 80{\%} of the children, with no individual AUC0-24hr less than 15μg×h/ml. Results: Unboosted ATV capsules satisfied pharmacokinetic criteria at a dose of 520mg/m for those aged more than 2 to 13 years or less and 620mg/m for those aged more than 13 to 21 years or less. ATV/r capsules satisfied criteria at a dose of 205mg/m for those aged more than 2 to 21 years or less. ATV/r powder satisfied criteria at a dose of 310mg/m for those aged more than 2 to 13 years or less, but pharmacokinetics in those aged 2 years or less were highly variable. Conclusion: Body surface area-determined doses of ATV capsules and of ATV/r powder and capsules provide ATV exposures in children of more than 2 years that approximate concentrations in adults receiving ATV/r.",
keywords = "HIV, atazanavir, children, pediatrics, pharmacokinetics, protease inhibitor",
author = "Kiser, {Jennifer J.} and Rutstein, {Richard M.} and Pearl Samson and Bobbie Graham and Grace Aldrovandi and Mofenson, {Lynne M.} and Elizabeth Smith and Steven Schnittman and Terry Fenton and Brundage, {Richard C.} and Fletcher, {Courtney V}",
year = "2011",
month = "7",
day = "31",
doi = "10.1097/QAD.0b013e328348fc41",
language = "English (US)",
volume = "25",
pages = "1489--1496",
journal = "AIDS",
issn = "0269-9370",
publisher = "Lippincott Williams and Wilkins",
number = "12",

}

TY - JOUR

T1 - Atazanavir and atazanavir/ritonavir pharmacokinetics in HIV-infected infants, children, and adolescents

AU - Kiser, Jennifer J.

AU - Rutstein, Richard M.

AU - Samson, Pearl

AU - Graham, Bobbie

AU - Aldrovandi, Grace

AU - Mofenson, Lynne M.

AU - Smith, Elizabeth

AU - Schnittman, Steven

AU - Fenton, Terry

AU - Brundage, Richard C.

AU - Fletcher, Courtney V

PY - 2011/7/31

Y1 - 2011/7/31

N2 - Objective: To describe the pharmacokinetics of atazanavir (ATV) and ritonavir-boosted ATV (ATV/r) in children aged 91 days to 21 years. Design: A phase I/II, open-label, multicenter study of once-daily ATV and ATV/r as part of combination antiretroviral treatment in HIV-infected treatment-experienced and treatment-naive children. Setting: Sites in the United States and South Africa. Participants: One hundred and ninety-five children enrolled; 172 had evaluable ATV pharmacokinetics on day 7. Intervention: Children were entered in age, dose, and formulation (powder or capsule) cohorts. Intensive pharmacokinetic sampling occurred 7 days after starting ATV. ATV doses were increased or decreased if the 24-h area under the concentration time curves (AUC0-24hr) were less than 30 or more than 90μg×h/ml, respectively. Main Outcomes: Cohorts satisfied protocol-defined pharmacokinetic criteria if the median ATV AUC0-24hr was 60μg×h/ml or less, and AUC0-24hr and ATV concentrations 24-h postdose (C24) were more than 30μg×h/ml and at least 60ng/ml, respectively, in at least 80% of the children, with no individual AUC0-24hr less than 15μg×h/ml. Results: Unboosted ATV capsules satisfied pharmacokinetic criteria at a dose of 520mg/m for those aged more than 2 to 13 years or less and 620mg/m for those aged more than 13 to 21 years or less. ATV/r capsules satisfied criteria at a dose of 205mg/m for those aged more than 2 to 21 years or less. ATV/r powder satisfied criteria at a dose of 310mg/m for those aged more than 2 to 13 years or less, but pharmacokinetics in those aged 2 years or less were highly variable. Conclusion: Body surface area-determined doses of ATV capsules and of ATV/r powder and capsules provide ATV exposures in children of more than 2 years that approximate concentrations in adults receiving ATV/r.

AB - Objective: To describe the pharmacokinetics of atazanavir (ATV) and ritonavir-boosted ATV (ATV/r) in children aged 91 days to 21 years. Design: A phase I/II, open-label, multicenter study of once-daily ATV and ATV/r as part of combination antiretroviral treatment in HIV-infected treatment-experienced and treatment-naive children. Setting: Sites in the United States and South Africa. Participants: One hundred and ninety-five children enrolled; 172 had evaluable ATV pharmacokinetics on day 7. Intervention: Children were entered in age, dose, and formulation (powder or capsule) cohorts. Intensive pharmacokinetic sampling occurred 7 days after starting ATV. ATV doses were increased or decreased if the 24-h area under the concentration time curves (AUC0-24hr) were less than 30 or more than 90μg×h/ml, respectively. Main Outcomes: Cohorts satisfied protocol-defined pharmacokinetic criteria if the median ATV AUC0-24hr was 60μg×h/ml or less, and AUC0-24hr and ATV concentrations 24-h postdose (C24) were more than 30μg×h/ml and at least 60ng/ml, respectively, in at least 80% of the children, with no individual AUC0-24hr less than 15μg×h/ml. Results: Unboosted ATV capsules satisfied pharmacokinetic criteria at a dose of 520mg/m for those aged more than 2 to 13 years or less and 620mg/m for those aged more than 13 to 21 years or less. ATV/r capsules satisfied criteria at a dose of 205mg/m for those aged more than 2 to 21 years or less. ATV/r powder satisfied criteria at a dose of 310mg/m for those aged more than 2 to 13 years or less, but pharmacokinetics in those aged 2 years or less were highly variable. Conclusion: Body surface area-determined doses of ATV capsules and of ATV/r powder and capsules provide ATV exposures in children of more than 2 years that approximate concentrations in adults receiving ATV/r.

KW - HIV

KW - atazanavir

KW - children

KW - pediatrics

KW - pharmacokinetics

KW - protease inhibitor

UR - http://www.scopus.com/inward/record.url?scp=79960565299&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960565299&partnerID=8YFLogxK

U2 - 10.1097/QAD.0b013e328348fc41

DO - 10.1097/QAD.0b013e328348fc41

M3 - Article

VL - 25

SP - 1489

EP - 1496

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 12

ER -