Background: There are no previous data describing nelfinavir and lamivudine pharmacokinetics in neonates treated with weight-band dosing regimens.
Design: Pharmacokinetic study of nelfinavir and lamivudine pharmacokinetics in infants during the first 2 weeks of life treated with weight-band dosing regimens.
Methods: Intensive 12-hour pharmacokinetic profiles were performed between either days 4–7 or days 10–14 of life in 26 Brazilian infants.
Results: Pharmacokinetic data were obtained from 26 infants who received median (range) per kg doses of 58.8 (48.4–79.0) mg/kg for nelfinavir and 2.0 (1.5–3.2) mg/kg for lamivudine. Median nelfinavir 12-hour AUC (AUC0-12) was 25.5 (1.7–183.5) μg*h/mL and median 12-hour concentration (C12h) was 1.09 (<0.04–14.44) μg/mL. AUC0–12 was less than 15 μg*h/mL (the 10% for adults) in 12 infants (46%). Median lamivudine AUC0–12 was 7.8 (2.7–15.6) μg*h/mL and median C12h was 0.23 (<0.04–0.74) μg/mL.
Conclusions: Lamivudine pharmacokinetic parameters observed in this study were consistent with those seen in other studies of neonates. While median nelfinavir AUC and C12h in these neonates were above the exposure targets, interindividual variability in nelfinavir exposure was large and nelfinavir exposure failed to meet the exposure targets in 46% of infants.
From the *Department of Pediatrics, Boston University School of Medicine, Boston, MA; †Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA; ‡Infectious Diseases Department, Hospital Geral de Nova Iguaçu, Nova Iguaçu and Laboratório de AIDS e Imunologia Molecular/FIOCRUZ, Rio de Janeiro, Brazil; §Division of Immunology, Department of Pediatrics, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; ¶Instituto de Pesquias Clinica Evandro Chagas/Fiocruz Institute, Rio de Janeiro, Brazil; ∥Department of Pediatrics, University of California, San Diego School of Medicine and Skaggs School of Pharmacy & Pharmaceutical Sciences; **National Children's Study, NICHD, NIH, DHHS, Bethesda, MD; ††Adolescent, and Maternal AIDS Branch, NICHD, NIH, DHHS, Bethesda, MD; ‡‡Clinical Trials Area, Westat Inc, Rockville, MD.
Accepted for publication March 24, 2011.
Supported by NICHD Contract HHSN267200800001C (NICHD Control N01-HD-8-0001) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contract NO1-HD33345), and co-sponsored by the HIV Prevention Trials Network (HPTN) and the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group.
Reprints: Mark Mirochnick, MD, Boston Medical Center, 771 Albany Street–Dowling 4N, Room 4111, Boston, MA 02118. E-mail: email@example.com.
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