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

15 Scopus citations

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

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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., Smith, E., Schnittman, S., Fenton, T., Brundage, R. C., & 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